SURFiN Program Lab Opportunities

Mentor: Harpreet Kaur
Mentor Role: Research Assistant Professor
Principal Investigator: Catherine Kaczorowski
Institution: University of Michigan
Location: Ann Arbor, MI
Lab Website: http://kaczorowski.lab.medicine.umich.edu

Project Description: Gut microbiota manipulation and peripheral inflammation in Alzheimer disease

Alzheimer disease (AD) is multifactorial disease, characterized by cognitive dysfunction and progressive memory decline. It is caused by a complex interaction between genetic, lifestyle and environmental risk factors. Recent studies suggest the involvement of gut microbiota in regulation of neuroinflammation and neurodegeneration in AD. Our current project involves understanding the sex difference in gut microbiota manipulation in AD. Previously, using a mouse of AD, we found that microbiota manipulation using probiotic from 2-4 months of age improved memory and decreased amyloid beta plaques, gliosis and brain cytokines in females but not in male mice. Interestingly, probiotics had minimal effects on gliosis, memory or Aβ plaque load in old females and male AD mice. Based upon these findings, we hypothesize that sex hormones contribute to both sex and age differences in response to probiotic manipulation. Currently, we are performing fecal microbiota transplantation (FMT) from younger AD females fed with probiotic to older AD mice. Along with it, in order to test direct involvement of gut microbes in AD, we are performing FMT from diseased to non-disease mice and doing neurobehavioral testing (for anxiety, learning and memory). Following the completion of behavior testing, tissues will be harvested for biochemical and molecular studies.

Mentor Biography: Harpreet Kaur is a research assistant professor working with Catherine Kaczorowski in the Department of Neurology, at the University of Michigan . She obtained her Ph.D. in biochemistry from Panjab University, India and did five-year postdoctoral fellowship at the University of North Dakota with Colin Combs. Her research involves a multidisciplinary approach to investigate the neuroprotective/therapeutic potential of natural products such as lycopene, curcumin and probiotics in neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease (AD). For the last six years, her research is focused on understanding if and how altered gut microbiota influence cognitive functions and disease progression in mouse models of AD. Her previous research findings provide evidence that the enteric nervous system, in addition to the central nervous system, is affected in AD, supporting the role of gut-brain axis in pathophysiology of AD. Currently, Kaur is investigating the complex interactions between the host genetics, environmental factors (diet, gut microbiota) and AD. She has received several awards including best paper and travel awards from the Asian Pacific Society for Neurochemistry (APSN) and the International Brain Research Association Asia Pacific Research Committee (IBRO-APRC). In 2017, she received anAlzheimer’s Association Research Fellowship (2017-2020). In 2022, she received another Alzheimer’s Association Research Fellowship award) to investigate sex dependent effects of gut microbiota manipulation in AD.

Eligibility: Students are allowed to work up to eight hours per day and no more than 20 hours per week when school is in session.

Mentor: Surjeet Singh
Mentor Role: Postdoctoral Associate
Principal Investigator: Catherine Kaczorowski
Institution: University of Michigan
Location: Ann Arbor, MI
Lab Website: http://kaczorowski.lab.medicine.umich.edu

Project Description: Identifying neural signatures of cognitive resilience

Alzheimer’s disease (AD) is a neurodegenerative condition associated with aggregation of two major proteins, amyloid beta and microtubule-associated protein, tau. Limited effective long-term pharmacologic therapy for prevention and treatment of AD suggests a lack in understanding of the pathophysiology of this disease. Cognitive resilience to AD is a phenomenon whereby cognitive functioning is better than predicted based on genotype and/or advanced neuropathology, likely because of the presence of as-yet-unidentified genetic factors. Using a set of human relevant diverse AD mouse models, we determined that cognitive resilience is associated with the apolipoprotein E (ApoE) genotype. This study aims to investigate the mechanisms whereby this protective variant of ApoE alters memory networks and make some individuals resilient to cognitive decline in AD. Using silicon probes we will measure neural activity from hippocampus and prefrontal cortex in these mice during sleep and cognitive tasks, and identify changes associated with resilience. Further, we will investigate pathological changes in brain and identify if a certain type of AD pathology, or a specific combination of pathologies could alter neural and cognitive function. This will provide us with novel insights into the mechanism of cognitive resilience critical for prioritizing new drug targets and strategies for AD treatments.

Mentor Biography: Surjeet Singh is a postdoctoral associate in the lab of Catherine Kaczorowski at University of Michigan. Singh completed both his bachelor’s and master’s degrees in electronics and communication engineering before receiving his doctorate in neuroscience from the University of Lethbridge, Canada. Singh’s research focuses on understanding how age, genetic variance and other environmental risk factors impact memory/cognition related brain networks in neurodegenerative diseases, particularly Alzheimer’s disease (AD). For his research Singh uses a wide range of engineering (signal processing, machine vision, machine learning and deep learning) and computational approaches combined with in vivo electrophysiology, in vivo imaging and behavioral methods. He has received numerous awards, including the MHRD-GATE scholarship (2008-2010), DRDO Golden Jubilee Student Competition award (2009), the Vice-Chancellor’s International Scholarship for Research Excellence from the University of Nottingham (2016), and the Campus Alberta Neuroscience Entrepreneurial Seed Grant (2020). In 2022, Singh was awarded an Alzheimer’s Association Research Fellowship to investigate the mechanisms by which a coding variant in the receptor binding domain of ApoE promotes cognitive resilience to autosomal dominant mutations known to cause AD. Singh also has several years of experience in teaching and mentorship (high school, undergraduate and graduate students).

Eligibility: Students are allowed to work up to eight hours per day and no more than 20 hours per week when school is in session.

Mentor: Stephanie Boas
Mentor Role: Postdoctoral Fellow
Principal Investigator: Catherine Kaczorowski
Institution: University of Michigan
Location: Ann Arbor, MI
Lab Website: http://kaczorowski.lab.medicine.umich.edu

Project Description: Genetic mechanisms controlling resilience to Huntington’s disease

This project will focus on identifying drivers of resilience to Huntington’s disease (HD). We have generated a novel mouse panel by crossing an HD mouse line to the genetically-diverse BXD panel for a systems genetic approach to identify modifiers that contribute to HD resilience in a ‘humanized’ mouse population. To quantify resilience across this panel, we are evaluating BXD substrains carrying the HD transgene on various cognitive and motor tasks. The BXD panel allows for quantitative trait loci mapping to correlate genetic variants to a given phenotypic outcome. We will investigate targets identified through trait mapping to inform follow-up genetic knockout/CRISPR editing strategies, using both in vitro and in vivo models. The Kaczorowski lab, and this project in particular, are ideal for a student in this program because there is an opportunity for exposure to diverse techniques, depending on the proclivities of the student. The SURFiN fellow could focus on any of the following: 1) behavioral phenotyping, learning to run mice on behavioral tasks; 2) cell culture assays on BXD cell lines; and/or 3) computational analyses (trait mapping, pathway modeling).

Mentor Biography: Stephanie Boas is a postdoctoral researcher in the lab of Catherine Kaczorowski at the University of Michigan. Her research interests focus on understanding cell-type-specific pathogenic mechanisms across neurodegenerative diseases, and how genetic risk factors differentially impact diverse cell types and regions of the brain. Boas has a strong background in molecular techniques and neurodegenerative disease processes. In her graduate work at the University of Alabama at Birmingham (UAB), she studied how heterogeneous neuronal subtypes are differentially affected in rodent models of Parkinson’s disease in the lab of Rita Cowell. She also took advantage of several informal and formal mentorship opportunities, such as training several Cowell Lab undergraduates in molecular techniques and science communication. She also mentored several summer students through UAB’s Summer Program in Neuroscience (SPIN) program. Additionally, she served as a teaching assistant for two semesters of biostatistics. Baos finds mentorship opportunities to be energizing, both to her individually, and to the lab as a whole. While she has had incredible opportunities throughout her education, she’s originally from a rural town in Illinois, so he understands what it’s like to have limited exposure to academic opportunities, and how much this exposure can influence young scientists. Boas is excited to be a part of programs like these that create such opportunities.

Eligibility: Students are allowed to work up to eight hours per day and no more than 20 hours per week when school is in session.

Mentor: Kevin Charland
Mentor Role: Graduate Student
Principal Investigator: Catherine Kaczorowski
Institution: University of Michigan
Location: Ann Arbor, MI
Lab Website: http://kaczorowski.lab.medicine.umich.edu

Project Description: Generation of mouse and human tri-cultures to test genes influencing the observed sex differences in Aβ42 pathology

In this project, we will be generating in vitro tri-cultures of neurons, astrocytes and microglia derived from both genetically diverse mouse embryonic stem cells (mESCs) and human induced pluripotent stem cells (hiPSCs) isolated from patients with Alzheimer’s disease (AD). Male and female mESCs will be utilized to investigate the influence of sex on various outcomes. hiPSCs will also be used to make organoids to model AD pathology in a 3D system. Cultures will be treated with beta amyloid 1-42 (Aβ42) and used to probe the influences of candidate genes that modify sex-specific differences in Aβ42 pathology. Cellular phenotypes of interest include inflammation, protein homeostasis, cellular senescence, mitochondrial functioning, cellular energetics (NAD+/NADH) and lysosomal functioning. Techniques used in this project will include various molecular assays, viral transfections, live cell imaging, immunocytochemical staining, neuronal functioning, gene expression, protein expression, computational biology, developing/optimizing derivation protocols from stem cells and general cell culturing practices. The ultimate goal of the project is to refine candidate genes identified from analyzing cortical Aβ42 abundance in AD-BXD mice and investigate the mechanisms through which they modify cellular response to Aβ42 pathology in a sex-specific and genetic background-dependent manner.

Mentor Biography: Kevin Charland is a second-year Ph.D. student in the neuroscience program at Tufts University. He received a bachelor’s degree in integrative neuroscience from SUNY Binghamton and a master’s degree in neuroscience from the University of Hartford. While he began his doctoral work in the Tufts neuroscience program at The Jackson Laboratory in Bar Harbor, Maine, he will be moving to the University of Michigan with the Kaczorowski lab. Hewill remain in the Tufts program as a visiting scholar. Charland’s current research interests include the influences of sex and genetic background in Alzheimer’s disease pathology with a current focus on cortical beta-amyloid 1-42 (Aβ42) pathology. He is also interested in the gut microbiome and its influence on the brain as well as using dietary interventions to help ameliorate various diseases. At Hartford, he received teaching assistantships for biology and anatomy/physiology labs and has experience mentoring undergraduate researchers in the lab he received his master’s degree studying the influences of a ketogenic diet on Alzheimer’s pathology. Additionally, he was awarded the William S. and Dorothy G. Wallace Memorial Award for Academic Achievement in Neuroscience twice during his time at the University of Hartford.

Eligibility: Students are allowed to work up to eight hours per day and no more than 20 hours per week when school is in session.

Mentor: Wei Niu
Mentor Role: Assistant Professor
Principal Investigator: Wei Niu
Institution: University of Michigan
Location: Ann Arbor, MI
Lab Website: https://niulab.weebly.com/

Project Description: Modeling autism and epilepsy using stem cells and brain organoids

One of the most fundamental impediments to understand pathogenic mechanisms of genetic disorders in human nervous system is the lack of accessibility to human brain tissue. To address this challenge, we have developed human stem cell and brain organoid models for testing gene variants that are strongly associated with autism or epilepsy. We employ a multi-disciplinary approach including cell biology, neuroscience and molecular biology, such as imaging, CRISPR/CAS9 gene editing, and transcriptome analysis. Our current focus is to determine how the loss of POGZ leads to developmental defects and altered inhibitory circuitry in the brain. POGZ is one of the genes which are most commonly associated with recurrent de novo variants in individuals with neurodevelopmental conditions, including autism , intellectual disability (ID) and epilepsy. In this project, we propose to differentiate patient induced pluripotent stem cells (iPSCs) and isogenic controls into two different human forebrain-like structures: dorsal human cortical organoids (dhCOs) and ventral human cortical organoids (vhCOs). We will fuse these two regional COs and monitor the migration of interneurons and the formation of cortical circuits in vitro using high spatiotemporal resolution live imaging and longitudinal MEA recordings. Through this study, we expect to define the cell types, developmental stages, and neural circuitry critical for POGZ-related pathogenesis. We will also compare the growth rate of brain organoids derived from patient with the ones derived from control iPSCs, and examine the cytoarchitectural features of brain organoids by immunostaining with antibodies against markers of ventricular zone radial glia, proliferating and dying cells, and neurons. We will measure the mRNA expression level of these critical cell markers of cortical development in these organoids using RT-qPCRs. The SURFiN fellow will be participating in designing, executing and analyzing the above mentioned experiments.

Mentor Biography: Wei Niu is an assistant professor (research track) in the Department of Neurology at the University of Michigan (UM). She received her doctorate in cell and molecular biology from the University of Texas at Austin. She trained as a postdoctoral fellow at Yale University with Michael Snyder on genomics. Following her training, she applied her expertise in genomics to study molecular mechanisms of autism as a research scientist in the group of James Noonan at Yale School of Medicine. Since 2016, she has been working with Jack Parent at UM to understand how genetic variants alter human brain development using human pluripotent stem cell (hPSC) derived brain organoid models, and to develop pre-clinical models of novel therapies for genetic pediatric brain disorders. Since she was promoted to research assistant professor in September 2020, Niu has been focused on the neurodevelopmental disorders caused by the mutations of either POGZ or PCDH19 genes. Her group generated the first POGZ loss-of-function hPSC lines using CRISPR/CAS9 gene editing. This led to the discovery that POGZ promotes both neural stem cell lineage progression in human cortical rosettes and migration of developing neuron. Furthermore, she has developed the first pre-clinical brain organoid model for neurodevelopmental epileptic disorder caused by the PCDH19 mutations. In addition to building out her research program as a new investigator, she has been actively mentoring undergraduate and graduate students from diverse cultural, social and economic backgrounds.

Eligibility: Students are allowed to work up to eight hours per day and no more than 20 hours per week when school is in session.

Mentor: Rene Caballero-Floran
Mentor Role: Research Investigator
Principal Investigator: Paul Jenkins
Institution: University of Michigan
Location: Ann Arbor, MI
Lab Website: https://pjenkinslab.org/

Project Description: Autism-associated polymorphisms in NaV1.2 channels alter their electrophysiological properties, impacting neuronal excitability

SCN2A and ANK2 are strong risk genes for autism. The voltage-gated sodium channel NaV1.2 (product of SCN2A) is located at the dendrites in mature neurons, where it promotes action potential backpropagation necessary for normal synaptic function. Ankyrin-B, (product of the gene ANK2) is an intracellular scaffolding protein that is highly enriched in the soma and distal dendrites. We recently discovered that ankyrin-B is the dendritic scaffold for NaV1.2, and that deleting ankyrin-B significantly reduced NaV1.2 dendritic localization. While we have identified disease-associated variants within the binding interface between the two proteins, not all the variants in the interface influenced the binding affinity of NaV1.2 to ankyrin-B, suggesting that they may influence channel function in other ways. Our research project involves performing whole-cell electrophysiological voltage-clamp recordings in mammalian cells to compare the biophysical properties of wild-type NaV1.2 channels to those of NaV1.2 channels with autism-associated polymorphisms that do not disrupt the binding to ankyrin-B. This is critical because changes in ion channel electrophysiological properties can influence neuronal excitability and synaptic function, and thus can contribute to the etiology of autism.

Mentor Biography: René Caballero-Florán is a research investigator in Paul Jenkins’ lab in the Department of Pharmacology at the University of Michigan. He has extensive research experience in pharmacology, with expertise in electrophysiology, biophysics and neuroscience. His research interests include performing integrative research to learn about the physiology of synapse formation, how genetic changes affect neuronal communication, and how this leads to neurological disorders. During his undergraduate studies, Caballero-Florán investigated the mechanisms of action of cannabinoids and opioids with the goal of developing new treatments for Parkinson’s. During research for his master’s degree (awarded with honors), he discovered that the dimerization of cannabinoid and dopamine receptors causes changes in signaling pathways that modulate neurotransmitter release in Parkinson’s disease. In addition, he worked in clinical research studies for the pharmaceutical industry to evaluate the efficacy, safety and pharmacokinetics of new drugs. During his doctorate, he performed in vivo electrophysiological recordings to predict changes in neuronal plasticity by measuring neurotransmitter release evoked by electrical pulses, allowing him to start new lines of research in his former lab. As a postdoctoral fellow, he enhanced electrophysiology practices and combined them with genetic and molecular biology techniques to describe the pathophysiological mechanisms involved in neurological and psychiatric disorders.

Eligibility: Students are allowed to work up to eight hours per day and no more than 20 hours per week when school is in session.

Mentor Name: Kyle Thomas
Mentor Role: Graduate Student
Principal Investigator: Samuel Sober
Institution: Emory University
Location: Atlanta, GA
Lab Website: https://scholarblogs.emory.edu/soberlab/

Project Description: Skilled movements require us to integrate both internal and external constraints as we navigate through the world. This integration takes place at multiple levels of the neuromuscular system to ensure success of the intended behavior. However, the activity of spinal motor neuron populations, which directly innervate muscles, remains largely unknown. Recent evidence suggests that the timescale of activity may play a role in how we adjust and adapt our behaviors. This research project aims to investigate this idea by recording motor units (the muscle fibers innervated by a single motor neuron) during behaviors including locomotion and grooming. The SURFiN fellow would be directly involved in establishing the behavioral protocol and modifying existing analytical tools for assessing both the behavioral kinematics and the neural activity.

Mentor Biography: Kyle Thomas is a biomedical engineering graduate student in the laboratory of Sam Sober in the Department of Biology at Emory University. His current work focuses on understanding how sensorimotor adaptation contributes to basic motor skills through spinal motor networks. Previously, he studied biomedical and systems engineering at Washington University in St. Louis. He is interested in creating accessible neuro-technologies and generating more conversation surrounding neuro-ethics. He has grown a lot from the mentors in his life and hopes to carry that forward with new students, including those he has already mentored through SURFiN.

Eligibility: N/A

Mentor Name: Kofi Vordzorgbi
Mentor Role: Graduate Student
Principal Investigator: Samuel Sober
Institution: Emory University
Location: Atlanta, GA
Lab Website: https://scholarblogs.emory.edu/soberlab/

Project Description: Motor actions can be described as a sequence of smaller, discrete actions, with different actions sometimes following similar trajectories to each other in space than to others. Additionally, some abilities like human speech are characterized by syllables and discrete phonemes that are arranged in variable ways to generate the variety of words and sequential syntactical rules we use. The Bengalese finch (BF) song is similar in these respects in that it, too, has multiple sequences of varying similarities and can variably string together syllables in its song. Additionally, BFs have a specialized nucleus, called the HVC, in their brains that plays a master role in generating variable neural sequences underlying this vocal behavior. This makes the BF a great model for studying neural control of sequential behavior. Kofi’s thesis aims at describing the role of interneurons within HVC in modulating the variable neural signals sent out of the nucleus. The project broadly involves surgically implanting chronic recording electrodes into HVC, recording from the singing bird under a variety of natural and experimental conditions, and computationally isolating neural spikes and characterizing their dynamics. Each of these aspects provides a unique opportunity for the SURFiN fellow to attain broad skills in planning and performing assays, as well as gaining computational skills.

Mentor Biography: Kofi Vordzorgbi is an M.D./Ph.D. student who is currently in the second year of his graduate school phase in the neuroscience program at the Emory University School of Medicine. He has been working for a year in Samuel Sober’s lab, which broadly studies mechanisms and dynamics of neural control of motor behavior using songbird and mouse models. Vordzorgbi’s thesis project specifically focuses on how the songbird brain nucleus HVC (used as a proper name) generates variable neural codes in the control of a variety of related, but divergent vocal sequences. Vordzorgbi graduated from Morehouse College in 2015 with a bachelor’s degree in music/pre-medicine, and earned a master’s degree in biomedical science (neuroscience) from the Icahn School of Medicine at Mount Sinai in 2018. His goal is to be a neurologist who studies and treats diseases characterized by neuroinflammation, movement disorders or neurodegeneration. Additionally, he hopes to attain skills in sampling in vivo brain activity and using computational means to decode neural control of behavior and cognition in these disease contexts.

Throughout his college and graduate school years, Vordzorgbi has engaged in mentorship of high school and college students,helping them pursue their careers in STEM. More importantly, he has benefited immensely from invaluable mentorship from doctors, researchers, his current and former principal investigators, and colleagues. He hopes to continue to provide this service to future scientists.

Eligibility: N/A

Mentor Name: Kaitlin (KC) Jacobson
Mentor Role: Graduate Student
Principal Investigator: Bilal Haider
Institution: Georgia Institute of Technology
Location: Atlanta, GA
Lab Website: haider.gatech.edu

Project Description: Most individuals diagnosed with autism show impairments in responding to sensory information. It is unclear if this is only due to altered neural processing of sensory information, or if other non-sensory factors (such as impaired motivation or alertness) also contribute. Addressing this question requires careful control and measurement of behavioral responses to sensory input, along with control of non-sensory motivational factors. By performing these studies in animal models of autism, we can also directly measure neural sensory processing during the behavior. The goal of this project is to examine the influence of motivation and alertness on visually-guided behavior in a human-relevant transgenic mouse model of autism. We have developed a task where water-restricted mice report perception of a visual stimulus by licking for water reward. The stimuli are presented at different contrasts and locations to quantify behavioral performance across a range of sensory conditions, while simultaneously measuring alertness and behavioral engagement with high-speed video of the pupil. The SURFiN fellow will learn how to train our autism model, as well as wildtype mice, and test if factors of alertness and thirst motivation during the task contribute to impaired sensory perceptual behavior in our mouse model of autism.

Mentor Biography: Kaitlin (KC) Jacobson is a second year graduate student in the Georgia Institute of Technology (GT) Bioengineering program. She holds a bachelor’s degree in chemical biomolecular engineering from GT, and was a recipient of several awards at GT, including the President’s Fellowship, Zell Miller Scholarship, National Merit Scholarship, Petit Undergraduate Research Scholarship, and has co-authored two publications. Jacobson was admitted to the graduate program as a scholar in the GT/Emory NIH T32 Computational Neuroscience Training Program, and has recently earned a Global Impact Award from the Achievement Rewards for Academic Scientists (ARCS) Foundation. She has passed her qualifying examination, and her Ph.D. research investigates the neural basis of visual processing and visual behavior in cortical areas of neurotypical versus in mouse models of autism (SFARI-funded project). She also has shown significant drive and enthusiasm for mentorship of junior students.

Eligibility: N/A

Mentor Name: Katrina Nguyen
Mentor Role: Postdoctoral Fellow
Principal Investigator: Abigail Person
Institution: University of Colorado Anschutz Medical Campus
Location: Aurora, CO
Lab Website: personlab.org

Project Description: The cerebellum is a brain structure that is important for precise movement and precise thought. How it supports the rest of the brain in these functions is the focus of this project. We hypothesize that a microcircuit within the cerebellar cortex computes the distance between a goal and the current state of the animal. When the difference nears zero, the cerebellum generates a pulsatile signal that causes the action (or potentially thought) to land on target. The SURFiN fellow will work closely with a skilled postdoctoral fellow to collect and analyze two-photon calcium imaging data from two nodes within the network mentioned above. The specific experimental approach involves training mice to reach to targets at different angles from their body. They are head-fixed with cranial windows implanted in the skull to allow in vivo imaging of calcium indicators introduced through viral injections. While mice reach to directional targets, we record calcium transients in either molecular layer interneurons (hypothesized to integrate velocity signals to compute current position/state) or parallel fiber axons (hypothesized to compute goal). We will test whether these circuit elements encode the predicted signals, a key step toward identifying computations made by this circuit.

Mentor Biography: Katrina Nguyen is a bioengineer, working as a postdoctoral fellow at the University of Colorado Anschutz Medical Campus with Abigail Person and Diego Restrepo. She got her Ph.D. at Carnegie Mellon University where she developed an experimental platform and tracking algorithm to study the kinematics and basal ganglia contributions of motor learning. She is currently interested in exploring how circuitry in the cerebellum uses sensorimotor information to guide precise, goal-directed reaching in rodents.

Eligibility: N/A

Mentor Name: Joshua Tycko
Mentor Role: Postdoctoral Fellow
Principal Investigator: Michael Greenberg
Institution: Harvard University
Location: Cambridge, MA
Lab Website: https://greenberg.hms.harvard.edu/

Project Description: The brain and other organs communicate by secreting thousands of proteins that travel throughout the body and activate receptors on target cells, forming a biological transportation network of protein packages that must be routed to their intended recipient cells. While some secreted proteins, such as insulin, have been deeply studied, we previously lacked tools to track a large number of proteins’ movement in an animal. For this project, we will use newly developed technology to ask fundamental questions such as: “Are there “passport” sequences that permit a protein to cross the blood-brain barrier?” Answering such questions will help us better understand how distal tissues communicate with the brain and better deliver synthetic proteins for therapeutic applications.

During this project, the SURFiN fellow will gain experience in molecular biology techniques including DNA plasmid design and cloning, CRISPR, protein purification and sequencing. We will use Python and Bash scripting to analyze and visualize biological datasets. In addition to their mentor, the fellow will also meet regularly with leading neuroscientist Michael E. Greenberg and benefit from the rich environment of postdocs, graduate students and other early career researchers in the Greenberg Lab.

Mentor Biography: Joshua Tycko is a postdoctoral research fellow at Harvard Medical School who is developing scalable protein barcoding technology to enable multiplexed measurement of secreted proteins in animals. His goal is to uncover how circulating proteins are routed across biological barriers to reach specific cell types to better understand how cells communicate in healthy homeostasis and how those processes can be manipulated for genetic medicine. He received a Ph.D. in genetics from Stanford University where he developed a high-throughput recruitment approach that uncovered hundreds of human transcriptional effector domains that regulate gene expression. He and his collaborators also discovered new recombinases that can directly integrate large DNA into the human genome. Tyko previously worked in the biotechnology industry on measuring, modeling and mitigating CRISPR off-target activity to enable safer genetic medicines.

Tycko earned a bachelor’s degree in biological mathematics from the University of Pennsylvania, where he did undergraduate research on AAV gene therapy. He has served as a mentor to several undergraduate and graduate students and advised several teams of undergraduate students in the iGEM synthetic biology competition. His research has been supported by both NIH F99/K00 and NSF GRFP fellowships.

Eligibility: Students with visiting undergraduate student appointments (non-Harvard undergraduates) may only hold one appointment at Harvard Medical School. Visiting undergraduate students appointed by Harvard departments are not eligible to enroll in Harvard academic courses and their position at Harvard Medical School is solely based on research and research training.

Mentor Name: Luis Hernandez-Nunez
Mentor Role: Postdoctoral Fellow
Principal Investigator: Florian Engert
Institution: Harvard University
Location: Cambridge, MA
Lab Website: https://www.engertlab.org/

Project Description: Our project is focused on studying the neural mechanisms that mediate cardiac modulation of brain function and brain modulation of cardiac function from a systems-level perspective. Even though the heart-brain communication axis is central for homeostasis, our understanding of this pathway is limited to knowing some of the brain regions and neural populations involved in the process. We do not understand the computations carried out by the neural circuits within and between the cardioregulatory areas of the central, autonomic and intracardiac nervous systems. Using larval zebrafish as a model organism, we are pioneering systems-level studies of the neural circuits that mediate heart-brain communication. In this project, the SURFiN fellow will work with their mentor to develop high throughput assays for optogenetic control of cardiac function in freely moving larval zebrafish.

Mentor Biography: Luis Hernandez-Nunez is a Life Sciences Research Foundation (LSRF)
postdoctoral fellow and a Warren Alpert Distinguished Scholar in the laboratories of
Florian Engert and Mark Fishman at Harvard University. He is also a visiting scientist at the
HHMI Janelia Research Campus. He obtained his Ph.D. in systems biology from
Harvard in 2020. He conducted his doctoral research in Aravinthan Samuel’s lab, where he discovered molecules, cells and circuits that mediate thermal homeostasis in larval
Drosophila. Before graduate school, Hernandez-Nunez was an undergraduate and then a postbaccalaureate researcher in Thierry Emonet’s lab at Yale University. Prior to moving to the U.S., he studied mechatronics engineering at National University of Engineering in Peru.

Eligibility: Students with visiting undergraduate student appointments (non-Harvard undergraduates) may only hold one appointment at Harvard. Visiting undergraduate students appointed by Harvard departments are not eligible to enroll in Harvard academic courses and their position at Harvard is solely based on research and research training.

Mentor Name: Maxwell Elliott
Mentor Role: Postdoctoral Fellow
Principal Investigator: Randy Buckner
Institution: Harvard University
Location: Cambridge, MA
Lab Website: cnl.rc.fas.harvard.edu

Project Description: A major barrier to understand brain aging is that we currently lack precise ways to measure change in structure and function within individuals. This project will utilize recently developed rapid brain imaging scans to develop high-precision biomarkers of brain aging. Our goal will be to develop measures that can detect changes in an individual within six months. To accomplish this goal, we will leverage data from an ongoing longitudinal study in which dozens of rapid MRI scans are collected in healthy older adults, individuals with exceptional brain aging and individuals with neurodegenerative disease.

Mentor Biography: Before working at Harvard, Maxwell Elliott received a bachelor’s degree in psychology from the University of Minnesota and a Ph.D. in clinical psychology from Duke University. Elliott studies the psychology and neuroscience of individual differences in brain aging, neurodegenerative disease and mental illness. He is especially interested in developing brain imaging tools to precisely measure accelerated brain aging and risk for neurodegenerative disease so that we can accelerate our search for ways to maintain brain function.

Eligibility: Students with visiting undergraduate student appointments (non-Harvard undergraduates) may only hold one appointment at Harvard. Visiting undergraduate students appointed by Harvard departments are not eligible to enroll in Harvard academic courses and their position at Harvard is solely based on research and research training.

Mentor Name: Heather Kosakowski
Mentor Role: Postdoctoral Fellow
Principal Investigator: Randy Buckner
Institution: Harvard University
Location: Cambridge, MA
Lab Website: cnl.rc.fas.harvard.edu

Project Description: Recent advances in fMRI research has enabled precise definition and interrogation of networks that span association cortex in the cerebrum. It is unknown how the human striatum functions in relation to these networks. This project will focus on precision neuroimaging techniques to better understand human striatal organization and function within individuals. The undergraduate fellow for this project will learn about striatal function, have hands-on experience collecting and analyzing fMRI data, and gain a deeper understanding of networks associated with the striatum.

Mentor Biography: Heather Kosakowski received her B.A. in neuroscience from Wellesley College and a Ph.D. in cognitive science from MIT. Her work in the Buckner Lab focuses on how the striatum is organized and interacts with networks that span association cortices. In the future, Kosakowski hopes to combine her pre-doctoral training with her post-doctoral training to better understand infant brain function and organization.

Eligibility: Students with visiting undergraduate student appointments (non-Harvard undergraduates) may only hold one appointment at Harvard. Visiting undergraduate students appointed by Harvard departments are not eligible to enroll in Harvard academic courses and their position at Harvard is solely based on research and research training.

Mentor Name: Cheng Xue
Mentor Role: Staff Scientist
Principal Investigator: Marlene Cohen
Institution: University of Chicago
Location: Dalian, IL
Lab Website: http://cohenlab.com/

Project Description: How do we make choices? When do we make bad choices and why? The Cohen Lab studies perceptual decision-making and its underlying neuronal basis. We will build a “game-room” for our experimental animals in their home environment and record their choices when they voluntarily engage with our decision-making game. We will investigate choice behavior of the animals, and test two non-exclusive hypotheses about suboptimal choices: 1) that the perceived value of different options is contaminated by irrelevant processes (like visual images that are attention-grabbing), even when that does not help the animal get more rewards, and 2) that maintaining the flexibility required to switch between choice strategies imposes a neuronal cost worsens choice behavior in the short-term. The prospective student will help design and build the experiment system, collect and analyze data, use computational modeling to generate hypotheses about neuronal basis of this behavior, and work in tandem with ongoing rig-based electrophysiology projects to test model predictions.

Mentor Biography: Cheng Xue is currently a staff scientist in Marlene Cohen’s lab in the Department of Neurobiology at the University of Chicago. Xue received his bachelor’s and master’s degrees in physics from Nanjing University in China. He subsequently carried out his doctoral work at the German Primate Center, before joining the Cohen Lab as a postdoctoral researcher, where he is now a staff scientist. Xue is interested in decision-making behavior in the broad sense. He uses multi-faceted approaches including behaving monkey electrophysiology, computational modeling, and human psychophysics to study decisions in various aspects. Through these research experiences, Xue developed a keen interest in the apparently suboptimal decision-making strategies that are used by every species. Many of them may have cognitive origins, and therefore can potentially become a window to reveal important neuronal constraints in perception or decision-making. He believes research in this direction will inspire new treatment for various neurological disorders. Additionally, understanding how and why our brains do not produce the most accurate perception or the best judgments can inform better decision-making strategies.

Eligibility: N/A

Mentor Name: Marissa Scavuzzo
Mentor Role: HHMI Hanna H. Gray Postdoctoral Fellow
Principal Investigator: Paul Tesar
Institution: Case Western Reserve University
Location: Cleveland, OH
Lab Website: tesarlab.com

Project Description: Glial cell dysfunction in the “brain inside your gut”

Gut disturbances are unusually common in individuals with autism, however the basis of these gut defects are not yet known. As autism causes alterations to sociobehavioral function, much effort has been placed on understanding changes in the brain while intrinsic dysfunction of cells in people with autism in the gut remains unexplored. The enteric nervous system (ENS), colloquially known as the “second brain,” contains unique neuronal and glial cell types that collectively control gut function. We have generated three-dimensional intestinal “mini organs” innervated with the ENS from human induced pluripotent stem cells (iPSCs). In various conditions, including autism, glia in the brain can become reactive and polarize into a detrimental pro-inflammatory state that drives neuronal dysfunction and toxicity. Our preliminary data show that in autism, enteric glia upregulate key reactive markers compared to healthy controls. The presence of reactive enteric glia in autism has not previously been reported and their contribution to gastrointestinal dysfunction is unknown. In this project, our lab will use these innervated “mini-organs” to identify cellular and molecular changes in the enteric nervous system in autism and establish the prevalence of these defects across of panel of people with autism, both genetically defined and idiopathic .

Mentor Biography: Marissa Scavuzzo is a postdoctoral fellow in Paul Tesar’s lab at Case Western Reserve University School of Medicine. She received her bachelor’s degrees in neuroscience and biology before earning her doctorate in developmental biology from Baylor University College of Medicine. In the Tesar Lab, she is studying the network of nervous system cells inside your gut that has been referred to as “the second brain.” Using lab-grown organs to mimic the human intestine, Scavuzzo is mapping the impact of support cells called enteric glia across a wide range of conditions including autism. In the brain, glia regulate and protect neurons in many different ways and contribute to neurodevelopmental and psychiatric diseases, but their role in the gut is a new field. Her goal is to understand how enteric glia shift states in autism and how these cells respond to genetic, environmental and dietary changes. For this work, she has been awarded the HHMI Hanna H. Gray Fellowship, the New York Stem Cell Foundation Druckenmiller Fellowship and the Hartwell Foundation Fellowship. She has also served as an invited speaker at national and international venues.

Eligibility: N/A

Mentor Name: Jessica Herstine
Mentor Role: Graduate Student
Principal Investigator: Allison Bradbury
Institution: Nationwide Children’s Hospital
Location: Columbus, OH
Lab Website: https://www.nationwidechildrens.org/research/areas-of-research/center-for-gene-therapy/bradbury-lab

Project Description: One of the focuses of the Bradbury Lab at Nationwide Children’s Hospital is development of a gene therapy for a rare, genetic, neurological disease called vanishing white matter disease (VWM). VWM is an autosomal recessive disorder that leads to ataxia, spasticity, seizures, neurodegeneration and premature death in patients. Jessica Herstine serves as the project lead;her thesis work has included the establishment of novel in vitro models such as patient-derived astrocytes to understand disease etiology. Furthermore, her NIH TL1 training grant includes the use of the I98M toy mouse model to both characterize disease pathology and to evaluate gene therapy efficacy. Currently, neonatal mice are being treated via intra-cerebrospinal fluid (intra-CSF) administration of numerous potential gene therapy constructs. Continual analysis of therapeutic efficacy is evaluated through behavior assays and magnetic resonance imaging (MRI) to visualize disease progression and myelin loss. Additional experiments include post-mortem analysis to analyze histology, molecular disease markers and vector biodistribution. Future studies include dose ranging studies and toxicology testing of the lead candidate gene therapy. A SURFiN fellow would assist in molecular assays related to disease pathogenesis and attenuation with therapy, with additional insight to all aspects of this highly translational and transformative project.

Mentor Biography: Jessica A. Herstine received her bachelor’s degree in molecular genetics with a minor in neuroscience from The Ohio State University (OSU) in 2020. That same year, she matriculated as a Ph.D. student in OSU’s Molecular, Cellular, and Developmental Biology (MCDB) graduate program,where she joined the lab of Allison Bradbury at Nationwide Children’s Hospital. Herstein is now a Ph.D. candidate with active NIH TL1 training grant funding to investigate gene replacement therapy for a rare, genetic leukodystrophy called vanishing white matter disease. In her current role, she has become adept in numerous techniques such as direct fibroblast to neuron and astrocyte conversions, viral vector cloning, gene therapy application, mouse colony management, behavioral testing, and preclinical study design and execution. In addition, she has exploited ample opportunities for mentorship and teaching as a teaching assistant, through a leadership role in the MCDB Graduate Student Organization, and the Research Institute’s Trainee Association at Nationwide Children’s. Herstine thoroughly enjoys teaching and inspiring others through science and mentorship. She aspires to have a fulfilling career in academics as a professor and principal investigator so that she can help train the next generation of scientists.

Eligibility: N/A

Mentor Name: Carlos Orozco
Mentor Role: Graduate Student
Principal Investigator: Todd Roberts
Institution: University of Texas Southwestern Medical Center
Location: Dallas, TX
Lab Website: https://labs.utsouthwestern.edu/roberts-lab

Project Description: Social and communicative behaviors, like speech and language, are learned by mimicking the people who raise us and our extended social group. This imitative learning is commonly disrupted in neurodevelopmental disorders and is even an early indicator and diagnostic of autism. Using songbirds, whose song learning has similarities to human speech learning, our lab aims to understand neuronal mechanisms underlying autism. Recently, our lab demonstrated that suppressing the high-risk autism gene FoxP1 in a region necessary for song learning, led to impaired song learning due to blocked synaptic strengthening and plasticity particularly in the neurons projecting to the striatum.

However, there are many other high-risk autism genes whose cell-type specificity and cellular mechanisms have not been studied in vocal learning species. The goal of this project is to use the novel, high-throughput transcriptomic method, Multiplexed Error Robust Fluorescence In Situ Hybridization (MERFISH), to identify specific cell types across the entire forebrain region that differentially express up to 100 autism-risk genes from the SFARI database. Through this project, the fellow will learn about single-cell spatial transcriptomics, brain anatomy and the analysis of large datasets. The potential findings will guide further investigation of cell-type-specific molecular mechanisms underlying autism.

Mentor Biography: Carlos Orozco is a first-generation Mexican-American born and raised in the border town of El Paso, Texas. Their first research experience was through the Freshmen Research Initiative program at the University of Texas at Austin where they obtained their bachelor’s degree in neuroscience and biology. Through this program, they were part of Josh Beckham’s Virtual Drug Screening lab, where we used high-performance computing to find potential drugs more efficiently and affordably than conventional methods. I then worked in the lab of Laura Colgin studying how coordinated neuron firing is involved in sleep-dependent learning.

After graduating, Orozco completed a one-year postbaccalaureate program at the Max Planck Florida Institute (MPFI) for Neuroscience where they worked in the lab of Hiroki Taniguchi. they collaborated with the MPFI Electron Microscopy Core, directed by Naomi Kamasawa, to analyze the development and function of inhibitory neural circuits. Orozco is currently a fourth-year graduate student in the UT Southwestern (UTSW) Neuroscience program in the lab of Todd Roberts, where they research the development and evolution of cell types of vocal learning species. They are also the vice president of the Society for the Advancement of Chicanos/Hispanics and Native Americans in Science (SACNAS) chapter of UTSW.

Eligibility: N/A

Mentor Name: Anila M. D’Mello
Mentor Role: Early Career Scientist and Principal Investigator
Principal Investigator: Anila M. D’Mello
Institution: University of Texas Southwestern Medical Center
Location: Dallas, TX
Lab Website: dmellolab.com

Project Description: Impact of self-perception and perceptions of others on subjective and objective social task performance in autism.

Stigmatized groups are highly susceptible to reminders of relevant negative stigma and stereotypes, even when reminders are subtle. Awareness of these negative perceptions of others can detrimentally affect academic performance, self-perception and even life satisfaction with long-term consequences. Autism — a neurodevelopmental condition characterized by challenges in social cognition — is highly stigmatized. Negative stereotypes of poor social ability in autism are prevalent in the public sphere. Despite this, few studies have assessed how autistic individuals themselves perceive these stereotypes, and it is not known whether knowledge of these negative stereotypes affects how autistic individuals perform on tasks measuring social performance. The SURFiN fellow will use online testing in a large database of autistic individuals to test the impact of negative perceptions of others on subjective and objective social tasks in autism. This research constitutes an important first step in determining whether our current understanding of social ability in autism is in part distorted by external factors including awareness of negative perceptions by others.

Mentor Biography: Anila Maria D’Mello is an assistant professor and Jon Heighten Scholar in Autism Research within the Department of Psychiatry and Peter O’Donnell, Jr. Brain Institute at the University of Texas Southwestern Medical Center. She also holds an appointment in the Department of Psychology at the University of Texas at Dallas. D’Mello received her bachelor’s degree in psychology from Georgetown University, and her doctorate in behavior, cognition and neuroscience from American University. She completed postdoctoral training at the McGovern Institute for Brain Research at the Massachusetts Institute of Technology. D’Mello’s lab combines neuroimaging, neuropsychological assessment and behavioral experimentation to elucidate the brain circuits and mechanisms that support language and cognition in children and adults, and to understand how these circuits differ in neurodevelopmental conditions such as autism. The D’Mello Lab is particularly interested in the role of cerebro-cerebellar circuits in language and cognition across human development and disorders. D’Mello is currently a SFARI Bridge to Independence Fellow.

Eligibility: N/A

Mentor Name: Audrey Courreges
Mentor Role: Post-Baccalaurate Researcher
Principal Investigator: Anila M. D’Mello
Institution: University of Texas Southwestern Medical Center
Location: Dallas, TX
Lab Website: dmellolab.com

Project Description: Quantifying the impact of special interests on language performance in autistic children.

Special interests are highly motivating for autistic individuals and are associated with higher language network activation as well as better social communication outcomes. However, special interests are underutilized in research examining basic neurocognitive skills in autism. Although anecdotal reports suggest that autistic children talk more about their special interests, no one has carefully characterized whether special interests alter language behavior in autism, and what aspects of language behavior (e.g., lower level phonological processing vs. higher-order narrative processing) are most affected. This is of particular interest because language performance as measured by standardized assessments that are commonly used in autism
evaluations might not accurately reflect true language capacity in autistic children. The SURFiN fellow will quantitatively and qualitatively analyze semi-structured interviews of autistic children discussing their special interests and compare language patterns between topics of special interest and control conditions. This project will help us to (1) determine whether integrating special interests has benefits for language processing, and (2) understand the true capacity of language processing and production in autism.

Mentor Biography: Audrey Courreges is the lab manager in the D’Mello Lab at the University of Texas Southwestern Medical Center (UT Southwestern). She received her bachelor’s degree in psychology from Southern Methodist University, where she studied correlations between school format and mental health symptoms among autistic youth during the COVID-19 pandemic. Following a position administering neuropsychological assessments to autistic children, Courreges continued her research career at UT Southwestern to join the D’Mello’s Lab. Her research interests largely revolve around the neurocognitive abilities of autistic individuals. Currently, she wants to better understand the cognitive underpinnings of special interests in autism and how these interests differ from neurotypical interests. She hopes to better characterize how special interests function in the cognitive patterns of autistic individuals. Courreges enjoys sharing her enthusiasm for autism and neurocognitive research, and hopes to encourage her mentees to approach research with similar excitement and curiosity.

Eligibility: N/A

Mentor Name: Nicholas Scott Card
Mentor Role: Postdoctoral Scholar
Principal Investigator: Sergey Stavisky
Institution: University of California, Davis
Location: Davis, CA
Lab Website: https://neuroprosthetics.faculty.ucdavis.edu/

Project Description: Developing a brain computer interface to restore speech to anarthric people

The overall goal of this project is to develop a brain-computer interface that can restore the ability to communicate to people who have lost the ability to speak. Toward this goal, we aim to surgically implant neural recording devices into the brain of a clinical trial participant and then accurately decode their neural signals into words during attempted speech. This project is large in scope and combines principles of neural engineering, systems neuroscience, computational neuroscience, computer engineering and machine learning. There are a wide variety of sub-projects within this scope that would be appropriate for an undergraduate researcher of any experience level. Potential subprojects include processing and analyzing human neural data, developing a pipeline for facial tracking during experimental sessions, helping to create a realistic neural simulator to test out the decoder, and more. I will work with the SURFiN fellow to choose an appropriate subproject for them based on their preferences, experience and skill level.

Mentor Biography: Nicholas Scott Card is a postdoctoral scholar in the Department of Neurological Surgery at the University of California, Davis. He works in the Neuroprosthetics Lab, which is co-led by Sergey Stavisky and David Brandman. Card earned both a bachelor’s degree (2016) and a doctorate in bioengineering (2022) from the University of Pittsburgh, where he received training in neural engineering, systems neuroscience and computational neuroscience. His current research interests are centered around the development of a brain-computer interface to restore the ability to communicate to clinical trial participants with neurodegenerative diseases or brain injuries that prevent them from being able to speak. Card has been awarded multiple research fellowships during his undergraduate and graduate research career from the Center for Neuroscience at the University of Pittsburgh (CNUP) and the Center for the Neural Basis of Cognition (CNBC), which is a joint program between the University of Pittsburgh and Carnegie Mellon University. As a senior graduate student, Card helped mentor younger graduate students within his lab. As a relatively new postdoctoral scholar, he is actively applying to postdoctoral research fellowships to further enhance his training as both a scientist and a mentor.

Eligibility: If the fellow is a UC Davis student, they must carry at least a half-time course load. When classes are in session, they may work up to 19.5 hours per week.

Mentor Name: Daril EVan Brown II
Mentor Role: Postdoctoral Research Fellow
Principal Investigator: Sergey Stavisky
Institution: University of California, Davis
Location: Davis, CA
Lab Website: https://neuroprosthetics.faculty.ucdavis.edu/

Project Description: Pioneering next generation brain recordings in humans

In this project, our lab will be pioneering research using next-generation high density electrodes, called micro arrays, to record neural activity from human subjects. These micro arrays will enable us to isolate and characterize the activity of single neurons during speech, improving our understanding of the neuronal anatomy and function of the brain regions involved. The goal of this research is to develop therapeutic systems that allow people with lost or diminished ability to speak to communicate again. This technology also has the potential of assisting surgeons in achieving greater precision when localizing and operating on parts of the brain where millimetric precision is necessary. This project is multidisciplinary, spanning neural engineering, neuroscience, medicine, machine learning, mechanical engineering, and audio processing. There are several potential sub-projects including processing and analyzing human data and designing devices to facilitate using these next-generation devices in the operating room. We will work with the SURFiN fellow to design a project that is both appropriate for their current skill set and designed to equip them with the experiences and skills necessary for their career aspirations.

Mentor Biography: Daril EVan Brown II is a postdoctoral research fellow in the Department of Neurological Surgery at the University of California, Davis,under the dual mentorship of Sergey Stavisky David Brandman. Awarded an NSF Graduate Research Fellowship and a UC-HBCU Fellowship, Brown has a unique background, having earned his bachelor’s degree in mechanical engineering from Howard University, and both a master’s degree in bioengineering and a doctorate in electrical engineering (with a specialty in medical devices and systems) from the University of California, San Diego. His postdoctoral research focuses on developing and deploying novel interactive experimental paradigms to understand the neural mechanisms of naturalistic speech to help develop next-generation communication neuroprosthesis for humans. His extensive mentorship and outreach efforts earned him induction into the Bouchet Honors Society. Many of his mentees have gone on to Ph.D. programs across the country. A three-time UCSD Grad Slam finalist, Brown is a strong advocate for science literacy and accessibility, and was recently featured on the KPBS Rad Scientist podcast. His leadership both inside and outside of the lab earned him recognition as a class of 2022 Siebel Scholar for Bioengineering. He is currently a NSF funded ASEE eFellow.

Eligibility: If the fellow is a UC Davis student, they must carry at least a half-time course load. When classes are in session, they may work up to 19.5 hours per week.

Mentor Name: Gerarda Cappuccio
Mentor Role: Postdoctoral Fellow
Principal Investigator: Mirjana Maletic-Savatic
Institution: Baylor College of Medicine
Location: Houston, TX
Lab Website: www.thinksavatic.org

Project Description: Mapping cell type-specific lipid dysregulation in 16p11.2 deletion syndrome

Lipids are a broad class of species essential for proper cell structure, energy metabolism and signaling, playing critical role in brain cell function. Our lab studies neurogenesis and how lipid metabolism affects generation of neurons during early development, adulthood and in disease. Here, we focus on the 16p11.2 deletion syndrome that arises because of copy number variations of the 16p11.2 genetic locus, causing several neurodevelopmental and psychiatric disorders. This locus contains different genes associated with lipid metabolism regulation (FAM57B, FBP2, ALDOA), and we hypothesize that deletion of these genes leads to cell type (neuron, astrocyte, neuroprogenitor)-specific lipid dysregulation manifesting in aberrant cell type-specific function and activity. We will test this hypothesis in forebrain organoids from patients with 16p11.2 deletion and isogenic controls. We will identify which lipid classes are most perturbed using cell-type specific lipidomics and imaging mass spectrometry. We will correlate these data with single cell transcriptomics and spatial transcriptomics, to identify specific pathways perturbed in 16p11.2 deletion. Further, as lipids are major part of cell membranes, we will perform atomic force microscopy to examine cell type-specific membrane properties. This project will thus provide broad scholarship and technical knowledge about the gene/metabolome dysregulation and brain function in 16p11.2 deletion.

Mentor Biography: Gerarda Cappuccio is a physician/scientist and a postdoctoral fellow at Baylor College of Medicine. She is a pediatrician subspecialized in genetics interested in neurodevelopmental metabolic disorders. Her goal is to find treatments for patients with untreatable genetic conditions. She discovered two new syndromes and coordinated clinical trials for them, leading to her receiving the 2022 John M. Opitz Young Investigator Award. She is now leveraging her clinical background and translational research experience to investigate the mechanisms of rare genetic syndromes, including copy number variants in 16p11.2 locus. She uses human models of disease, from brain organoids to organs-on-a-chip, to study how perturbations of metabolism affect neurogenesis and neuronal function. Utilizing a variety of new technologies from spatial transcriptomics and spatial metabolomics to nanoparticles for delivery of small molecules, her work paves the way toward new discoveries important for gene and pharmacological therapies. Cappuccio has published extensively, with 77 papers (30 as a first author), and received several awards for her work. She is also a keen mentor of undergraduate and graduate students, and actively promotes diversity and young women interested in STEM careers.

Eligibility: N/A

Mentor Name: JaeKyoon Kim
Mentor Role: Postdoctoral Research Scholar
Principal Investigator: Edwin Abel
Institution: University of Iowa
Location: Iowa City, IA
Lab Website: https://tedabel.lab.uiowa.edu/

Project Description: The 16p11.2 hemi-deletion (16p11.2 del) is one of the most common genetic changes associated with autism. Because the human 16p11.2 region is highly conserved in mice, we can model and study this genetic risk factor. Using this mouse model, we previously reported alterations in the structure and function of striatal circuits, which is consistent with recent studies reporting changes in striatal structure and function in people with autism. The striatum is the input structure of the basal ganglia, the key neural substrate for reward processing and motor control and these functions are often disrupted in individuals with autism. In this project, we will investigate the molecular mechanisms, cell-type specific effects and specific neuronal circuits that lead to distinct behavioral phenotypes in 16p11.2 del mice, applying a combination of genetically modified mouse models and targeted intra-striatal virus injections with complementary behavioral and biochemical techniques. We will also examine the biological basis for the sex differences in autism, which is more prevalent in males, using 16p11.2 del mice. Together, these findings will identify molecular mechanisms specific to the striatal dysfunction in autism. We hope that our research will help to develop novel therapeutic approaches for autism.

Mentor Biography: Jaekyoon Kim is a postdoctoral research scholar in the Department of Neuroscience and Pharmacology atCarver College of Medicine andIowa Neuroscience Institute at the University of Iowa. He received his bachelor’s degree in biochemistry from Yonsei University in Seoul, South Korea, and his master’s degree in biotechnology from Seoul National University. Hee received a Ph.D. in psychology, along with another master’s degree, at the University of Wisconsin, Milwaukee, where he worked with Karyn Frick, widely considered to be a world expert on the effects of estrogens on the brain and cognition. This background has given Kim the important ability to assess neuroscience from both a biomedical science perspective and a psychology perspective. Throughout his Ph.D., his work focused on the effects of sex steroid hormones, especially estrogen, on memory consolidation and he has become interested in sex differences in neurological disorders. Autism is a neurodevelopment condition with known sex differences. One of the most common genetic variations associated with autism is the deletion of the 16p11.2 chromosomal region, which can be faithfully modeled in mice. Using the 16p11.2 hemi-deletion mouse model, the Abel Lab at the University of Iowa revealed male-specific impairments in the acquisition of reward-dependent goal-directed behaviors. As a postdoctoral research scholar, Kim is working on elucidating the underlying mechanisms driving sex-dependent behavioral alterations in the 16p11.2 hemi-deletion mice.

Eligibility: Students not currently enrolled at the University of Iowa must enroll in the university for a minimum of one semester hour in order to receive funds through this program. Students may not work more than 20 hours per week during the academic calendar.

Mentor Name: Millie Rogers
Mentor Role: Graduate Student
Principal Investigator: Julia Dallman
Institution: University of Miami
Location: Coral Gables, FL
Lab Website: https://dallmanlab.weebly.com

Project Description: This project will use CRISPR/Cas9 to test whether disrupting zebrafish versions of a candidate human disease gene can produce disease-relevant phenotypes. Mutations are induced at the targeted gene locus, using designer IDT sgRNA and Cas9. Resulting phenotypes are quantified using a high-speed camera to track swimming performance and fluorescent microscopes to visualize neurons. Our lab uses zebrafish as our model organism because of their fully sequenced genome, high fecundity and transparency during embryogenesis. SURFiN fellow(s) accepted into our lab will learn a variety of practical lab skills, including familiarity with stable transgenic zebrafish, microinjection, genotyping, high-speed imaging and microscopy. They will also be trained in working with zebrafish under IACUC protocols. No prior laboratory experience is needed, only a strong work ethic and a desire to learn.

Mentor Biography: Millie Rogers is a second-year graduate student at the University of Miami. She received her bachelor’s degree from the University of Florida, where she studied the genetics underlying cochlear detoxification in the mammalian inner ear. She continues her research in genetics at University of Miami, where she is currently investigating the role of a newly identified human disease gene in degenerative neuromuscular phenotypes. Since beginning graduate school, she has taught general biology lab to approximately 30 students/class, leading undergraduates in learning and practicing experimental design and laboratory skills. She is also the proud mentor of three undergraduate students in her lab, whom she has trained in various laboratory techniques related to her research.

Eligibility: A fellow can have a student assignment, though they can only hold one work study position at a time.

Mentor Name: Manuel Beiran
Mentor Role: Postdoctoral Researcher
Principal Investigator: Ashok Litwin-Kumar
Institution: Columbia University
Location: New York, NY
Lab Website: http://lk.zuckermaninstitute.columbia.edu/

Project Description: Dynamics of recurrent neural networks with connectome-inspired constraints

In this project, we will develop models of recurrent neural networks whose connectivity between neurons is constrained by the existing data of neural connectivity from the fruitfly brain. We will use mathematical analysis to develop a theoretical framework and carry out numerical simulations using scientific programming to study the relationships between connectivity constraints, network dynamics and neural computation. We will train recurrent neural networks to perform time-varying computations. We will compare networks that are trained using different connectome-constraints, to try to understand the role of specific groups of neurons or synaptic patterns in the connectivity.

Mentor Biography: Manuel Beiran is a postdoctoral researcher in theoretical neuroscience at Columbia University’s Zuckerman Institute. He received a bachelor’s degree in physics from Universidad Autonoma de Madrid in 2014 and a master’s degree in computational neuroscience from the Bernstein Center for Computational Neuroscience in Berlin in 2016. In 2020, Beiran completed his Ph.D. in computational neuroscience at the Ecole Normale Superieure in Paris, supervised by Srdjan Ostojic. Since 2021, he has been a postdoctoral researcher at Columbia, supervised by Ashok Litwin-Kumar, as well as Kanaka Rajan at the Icahn School of Medicine at Mount Sinai. His research focus is in theoretical neuroscience, specifically in models of recurrent neuronal networks, and the links between connectivity, neural activity and computation. Currently, he is focusing on understanding how to effectively incorporate structural connectivity data into the modeling of neural networks, to suggest new experimental paradigms and test predictions at the neural level.

Eligibility: Columbia’s students are limited to working 20 hours per week during the academic semester.

Mentor Name: Qianying Wu and Na Yeon Kim
Mentor Role: Graduate Student and Postdoctoral Fellow (respectively)
Principal Investigator: Ralph Adolphs
Institution: California Institute of Technology
Location: Pasadena, CA
Lab Website: emotion.caltech.edu

Project Description: In this project, the SURFiN fellow will work closely with a graduate student (Qianying Wu) to explore blinks and pupil changes in response to audio and visual features from naturalistic movies and compare these measurements between autism and control participants.

The fellow will have access to two eyetracking datasets with naturalistic movie-watching tasks:1) a high-quality dataset collected with a desktop eyetracker (20 healthy participants and 20 participants with high-functioning autism), and 2) a large-sample dataset that will be collected over the internet using webcam-based eyetracking (as part of the SFARI 2022 Human Cognitive and Behavioral Science RFA we were recently awarded).

To analyze the data, the fellow will:1) identify blinks and pupil dilations from the eyetracking data, 2) extract audio and visual features from the video stimuli, 3) build individualized regression models to predict blinks and pupil changes using the video features, and 4) compare parameters from individualized models between the autism and control group.

In addition to the data analysis, the student will have extensive opportunities to interact with our autism participants, observe the ADOS administration, and gain experience in data collection. The student will also be co-mentored by principal investigator Ralph Adolphs and postdoctoral fellow Na Yeon Kim.

Qianying Wu Biography: Qianying Wu is a third-year graduate student in Caltech’s Social and Decision Neuroscience (SDN) program. Before joining Caltech, Wu received her bachelor’s degree in biosciences from the University of Science and Technology of China. Wu is interested in studying social behaviors in autism. Currently, she is completing her doctoral thesis on observational learning and naturalistic social attention, with a specific focus on autism. One of her major projects is to identify audiovisual features from naturalistic movies that drive eye gaze heterogeneity across autistic and neurotypical adults. In general, her research incorporates computational models to analyze behavioral, eye-tracking and fMRI data. In 2020, Wu received the Tianqiao and Chrissy Chen Graduate Fellowship Award at Caltech.

Na Yeon Kim Biography: Na Yeon Kim is a postdoctoral fellow working on eyetracking in autism. She is conducting in-lab eyetracking, web-based eyetracking, as well as eyetracking using smartphones. She has extensive experience mentoring summer students. She is funded by a SFARI grant to Ralph Adolphs.

Eligibility: Caltech’s GPA requirement is 2.5 for visiting students. Students must be non-graduating, be eligible for fall enrollment and not be under any disciplinary sanctions at their home school.

Mentor Name: Sara Caldas Martinez
Mentor Role: Graduate Student
Principal Investigator: Kate Hong
Institution: Carnegie Mellon University
Location: Pittsburgh, PA
Lab Website: thehonglab.com

Project Description: This project will involve the investigation of how tactile information is processed in cortical and subcortical brain areas, using in vivo electrophysiology, animal behavior and optogenetics.

Mentor Biography: Sara Caldas Martinez is a graduate student in biological sciences at Carnegie Mellon University (CMU). She holds a bachelor’s degree in biochemistry and a master’s degree in neuroscience from the Autonomous University of Barcelona, Spain.

Eligibility: N/A

Mentor Name: Aditi Jha
Mentor Role: Graduate Student
Principal Investigator: Jonathan Pillow
Institution: Princeton University
Location: Princeton, NJ
Lab Website: http://pillowlab.princeton.edu

Project Description: Reinforcement learning for modeling animal decision-making

Understanding decision-making is an important problem in neuroscience, and computational models have been crucial in uncovering factors underlying animal and human decision-making. This project will aim to model sequential decision-making in mice navigating in a labyrinth (using data collected by Rosenberg et al. 2021). Specifically, the SURFiN fellow will build on existing tools developed in the lab (see Ashwood and Jha et al. 2022) to model animal behavior in the labyrinth environment. They will work with their mentor to build reinforcement learning-based descriptive models to characterize how mice learn to navigate in the labyrinth. Furthermore, they will analyze their models to understand individual differences across mice when learning to navigate the environment, and to understand the factors that govern their decision-making strategies during learning. The fellow will learn the basics of reinforcement learning, as well as to implement these algorithms and apply them to real-data from mice.

Mentor Biography: Aditi Jha is a fourth-year graduate student at Princeton University. She is advised by Jonathan Pillow. Her current research interests include developing machine learning approaches to understand decision-making using both behavior and neural activity. She is also interested in understanding how learning shapes neural activity. Jha is the recipient of a Google Ph.D. Fellowship in computational neural and cognitive sciences.

Eligibility: N/A

Mentor Name: Albert Lin
Mentor Role: Postdoctoral Researcher
Principal Investigator: Mala Murthy
Institution: Princeton University
Location: Princeton, NJ
Lab Website: murthylab.princeton.edu

Project Description: Many animals engage in behaviors which require information from multiple sensory modalities such as vision and sound. These streams of sensory information are integrated in the brain to generate appropriate behavioral responses.

In the Murthy Lab, we employ the fruit fly as a model system for studying the neural bases of behavior and multi-sensory integration. During courtship, male flies will sing to female flies. The female will respond to the presence of the male based both on the audio stimulus of the courtship song and the visual stimulus of the male fly. We are interested in understanding the neural basis for this multi-sensory behavior, identifying where audio and visual information are combined in the neural circuits controlling female courtship behavior.

We have collected a large behavioral dataset observing interacting pairs of flies and quantified their behavior using automated computer vision methods. From these data, we identified behavioral syllables which require both visual and auditory inputs. The project we propose is an extension of this work, investigating which neurons are required for this multi-sensory behavior by performing behavioral experiments while optogenetically activating or silencing neurons, and identifying resultant behavioral changes. This project will involve animal handling, behavior quantification and data analysis.

Mentor Biography: Albert Lin received a bachelor’s degree. in physics, with a certificate in biophysics, from Princeton University, and their Ph.D. in physics from Harvard University. They are interested in how brains encode sensory information and generate behavior, and how anatomical connectomes constrain experimentally observed whole-brain activity. In their graduate work in Aravinthan Samuel’s lab, Lin developed methods for recording and analyzing ensemble-level and whole-brain neural activity in the nematode C. elegans.

Currently in Mala Murthy’s lab at Princeton, Lin studies brainwide multisensory integration in Drosophila melanogaster, the fruit fly. In pursuit of this objective, they employ two-photon imaging experiments, behavior quantification methods and whole-brain connectomics data.

As part of their research work at both Harvard and Princeton, Lin has mentored many undergraduate and graduate students. In addition to teaching them basic lab skills, they aim to provide research programs which allow students to experience a cross-section of the scientific process in microcosm, including literature, biology, experiments, data analysis and presentations of their work. Students that Lin has worked with have, in the course of their work, made significant contributions and become coauthors on publications.

Eligibility: N/A

Mentor Name: Pavel Tolmachev
Mentor Role: Postdoctoral Fellow
Principal Investigator: Tatiana Engel
Institution: Princeton University
Location: Princeton, NJ
Lab Website: N/A

Project Description: To gain insights into inner workings of nervous systems and brains, it is crucial to study animals within their natural habitat, facing the tasks they evolve to solve. However, animal studies are challenging, despite the tremendous advances in experimental methods including optogenetics and imaging techniques. Fully understanding and, thus, simulating simple animals like the roundworm C. elegans, which has only 302 neurons, remains unattainable. Furthermore, there is a general lack of methodology, techniques and principles for full-scale reverse-engineering of the nervous systems.

As an alternative, this project proposes evolving an artificial nervous system while adhering to evolutionary plausible constraints. The first concrete goal is to investigate which evolutionary constraints lead to the emergence of a modular-structured nervous system. The long-term goal is to evolve creatures that are simple enough to simulate, but complex enough to sharpen our methods for reverse-engineering the nervous systems.

The project involves creating an artificial environment and designing the rules of evolution. The SURFiN fellows will gain hands-on experience in artificial intelligence and evolutionary algorithms. The project will allow fellows to gain an in-depth understanding of simulation methods, and principles of neural design.

By the end of the project, fellows will have developed an appreciation for the complexity of the nervous system as well as directly witnessed evolution of artificial organisms. This project will provide a solid foundation for those who wish to pursue further research in the field of artificial intelligence and computational neuroscience.

Mentor Biography: Pavel Tolmachev is a postdoctoral Fellow in Tatiana Engel’s lab. He received a master’s degree in physics at the University of Moscow, followed by a Ph.D.in electrical and electronic engineering at the University of Melbourne in Australia (EEE department). Tolmachev is interested in motor control and the evolutionary perspective on the development of nervous systems. Additionally, he has extensive teaching experience, teaching a variety of subjects such as physics, calculus, probability theory, programming and digital Signal processing.

Eligibility: N/A

Mentor Name: Prakash Devaraju
Mentor Role: Research Associate
Principal Investigator: Nicholas Frost
Institution: University of Utah
Location: Salt Lake City, UT
Lab Website: nickfrostlab.org

Project Description: During behavior, the brain represents information across distributed circuits in a reliable manner. These representations are altered in neurodevelopmental disorders such as autism. Shank3 is a postsynaptic scaffolding molecule which is critical for synapse structure and function, and mutations in Shank3 result in autism and intellectual disability. We have previously shown that mice lacking Shank3 have abnormal activity and ensemble recruitment during social interactions, suggesting that emergent circuit properties are altered in these mice. Specifically, hyperdynamic ensemble recruitment in these mice results in inefficient and imprecise recruitment of neuronal activity. The primary goal of this project is to understand how this change in ensemble recruitment alters the routing of information within the prefrontal cortex during behavior. We utilize in vivo calcium recordings to record from large numbers of neurons in freely moving mice during social and anxiety-related behaviors to understand how the activity of neurons receiving input from upstream brain regions or projecting to specific downstream regions is altered in mutant mice. Students will learn to perform and analyze mouse behavioral experiments, collect calcium imaging datasets, and perform optogenetic and chemogenetic assays to alter circuit function.

Mentor Biography: Prakash Devaraju initially trained in veterinary medicine and surgery for eight years in India and later earned a Ph.D. in neuroscience in 2011 under the mentorship of Glenn I. Hatton and Todd A. Fiacco at the University of California, Riverside. His postdoctoral work in the laboratory of Stanislav S. Zakharenko at St Jude Children’s Research Hospital from 2011–2019 focused on hippocampus-dependent memory deficits in mice models of 22q11.2 deletion syndrome, a clinically relevant genetic abnormality which drives risk for neuropsychiatric disorders. Devaraju joined the Frost Lab at the University of Utah in the summer of 2022, where his research focuses on understanding how loss of autism-risk gene Shank3 alters the function of prefrontal cmicrocircuits during behavior. Specifically, Devaraju’s project aims to understand how these changes alter the recruitment of neuronal ensembles underlying social and anxiety-related behaviors. He has extensive experience in electrophysiology, calcium imaging, stereotactic surgeries and mouse behavior.

Eligibility: N/A

Mentor Name: Nathan Johnston
Mentor Role: Graduate Student
Principal Investigator: Nicholas Frost
Institution: University of Utah
Location: Salt Lake City UT
Lab Website: nickfrostlab.org

Project Description: Navigation requires an internal representation of the relative position of locations or objects so that an individual may utilize the most appropriate path to travel from one position to another. Hemispatial neglect is a condition characterized by deficits in the ability to attend to stimuli localized to one hemisphere — usually contralateral to a lesion in the parietal cortex — caused by a failure to reconcile allocentric and egocentric representations. Translation of information between these coordinate systems is critical both for us to reliably represent our surroundings, but also to permit flexible navigation strategies. To understand how the parietal lobe affects the representation of information on egocentric and allocentric coordinate systems we have developed a novel optogenetic model of hemispatial neglect, which permits us to record the activity of many neurons simultaneously during navigation and then measure how the activity of neurons in the prefrontal cortex and hippocampus changes following optogenetic silencing of the parietal cortex. Students will have an opportunity to learn to perform and analyze calcium data from freely moving animals engaged in a navigational task, as well optogenetic and chemogenetic modulation of circuit function.

Mentor Biography: Nathan Johnston is a second-year Ph.D. student in neurobiology at the University of Utah. He completed his bachelor’s degree in molecular and cellular biology at the University of Washington in 2020 and came to the University of Utah the following autumn. As an undergraduate, he worked in Garret Stuber’s lab at the University of Washington,where he used fluorescence in situ hybridization and functional transcriptomics to map cell types in the mammalian habenula. His graduate work focuses on using a combination of calcium imaging and computational techniques to understand how the computations underlying spatial navigation is altered in contralateral neglect.

Outside of the lab, Johnston is involved in a number of outreach and volunteer organizations including Science for U, which connects local students with scientists for mentorship through the school year, and the Three Minute Thesis competition which challenges graduate students to communicate their thesis work as clearly and succinctly as possible.

Eligibility: N/A

Mentor Name: Damhyeon Kwak
Mentor Role: Graduate Student
Principal Investigator: Nicholas Frost
Institution: University of Utah
Location: Salt Lake City, UT
Lab Website: nickfrostlab.org

Project Description: Social behavior entails dynamic and reciprocal interaction among two or more conspecifics, and adaptive social behavior is important in survival. As in other complex behaviors, social information related to social interactions is represented across distributed circuit within the brain. Autism is marked by maladaptive social functioning and abnormal social behavior is recapitulated in mice harboring mutations found in humans with autism, including the postsynaptic scaffolding molecule Shank3. In this project, we will characterize the social interactions in dyads of mice with different social contexts by varying familiarity and/or Shank3 genotypes. Along with the behavioral characterization, we will investigate how socially relevant information is routed in neural circuits by microendoscopic calcium imaging, focusing on understanding how coordinated activity of neural ensembles within the prefrontal cortex contributes to the communication of social information between brain regions by recruiting specific projections to downstream regions. We aim to elucidate the underlying mechanism of how social information is differentially represented according to different social contexts, and how it becomes dysfunctional in Shank3 mutants.

Mentor Biography: Damhyeon Kwak is a neuroscience Ph.D. student at the University of Utah. Before joining the Frost Lab, Kwak completed her master’s degree at Daegu Gyeongbuk Institute of Science and Technology in Gaegu, Korea. There, she utilized intracortical recordings to understand neural activity driving group behavior. Her work in the Frost Lab continues this focus on understanding circuit function underlying social behavior, and in particular she is interested in understanding how information related to social decisions and actions is altered by behavioral context, and in mouse models of neuropsychiatric disease.

Eligibility: N/A

Mentor Name: Anthony Sharkey Ricciardulli
Mentor Role: Graduate Student
Principal Investigator: Nicholas Frost
Institution: University of Utah
Location: Salt Lake City, UT
Lab Website: nickfrostlab.org

Project Description: GRIN2b is a high-risk autism gene that encodes a glutamate channel subunit. Mutations in GRIN2b are linked to autism and result in pronounced cortical malformation including in cortical lamination deficits, more rapid brain development, disruption of gyri and macrocephaly. We are interested in understanding how these changes at the synaptic and cytoarchitectural level affect the representation of information relevant to behavior. To answer these questions, we will utilize three-dimensional organoids generated from human-derived iPSCs to understand cytoarchitectural and circuit level changes that result in abnormal microcircuit function during behavior. Fellows will have the opportunity to learn techniques ranging from cell culture and cellular differentiation to in vivo imaging of cellular activity during behavior, with the ultimate goal of understanding how mutations in GRIN2b influence the growth and complexity of cortical circuits, and how these changes at the cellular and circuit level affect computations performed by cortical networks.

Mentor Biography: Anthony Sharkey Ricciardulli graduated from the University of California, Berkeley in 2017 with a B.S. in microbial biology. As an undergraduate, he investigated mechanisms of neurodevelopment during embryogenesis and developed expertise in cellular and molecular techniques. After graduation, he worked as a cellular engineer and tissue culture specialist in the laboratory of Fred Gage at the Salk Institute. There he generated patient-derived neurons to investigate how DNA repair processes and bioenergetics contribute to known neurodegenerative phenotypes using iPSC-derived human neurons. Prior to joining the Neuroscience Ph.D. Program at the University of Utah, he next worked at Sangamo Therapeutics, where his work focused on making AAV-delivered medicines targeting Parkinson’s disease, again using human iPSC-derived neurons to model this complex disease. Anthony joined the Neuroscience Ph.D. Program at the University of Utah where he has embarked on a joint project mentored by Nick Frost and Alex Shcheglovitov using three-dimensional human organoids to model circuit dysfunction in neurodevelopmental disorders.

Eligibility: N/A

Mentor Name: Yu-Ju Chen
Mentor Role: Postdoctoral Fellow
Principal Investigator: Hye Young Lee
Institution: University of Texas Health Science Center, San Antonio
Location: San Antonio, TX
Lab Website: https://lsom.uthscsa.edu/physiology/team-member/hye-young-lee-ph-d/

Project Description: Non-viral gene editing in brain disorders

Gene therapeutics have great potential for treating neurological disorders. However, challenges with delivery have limited their clinical potential. CRISPR/Cas9 is one of the most widely used gene editing tools due to the target specificity and simple design of sgRNA lending it both precision and ease of use. The Lee Lab has demonstrated that gene editing with Cas9 RNPs (Cas9 protein/sgRNA complexes) using non-viral delivery is possible in adult mouse brain (see Lee et al.2018, Nature Biomedical Engineering). Our current project aims to deliver Cas9 in a form of mRNA/sgRNA using non-viral vector in brain disorder mouse models given the promising features of mRNA delivery. To achieve this goal, aim 1 will focus on identifying the most efficient delivery vehicle by using reporter mice which can detect tdTomato expression as a result of gene editing. Aim 2 will focus on optimizing a dose, brain region, delivery efficiency, injection method and duration conditions. Aim 3 will focus on testing delivery vehicle in the preclinical model for brain disorders. We will use molecular, cellular and behavioral assessments to test aim 3.

Mentor Biography: Yu-Ju Chen is a neuroscientist who studies the molecular and cellular mechanisms of pathophysiology underlying neurodevelopmental disorders. He has a doctorate in biomedical science. After completing Ph.D. training in Guo-Jen Huang’s laboratory at Chang Gung University in Taiwan, he joined Hye Young Lee’s laboratory at the University of Texas Health Science Center at San Antonio as a postdoctoral research fellow in 2022. He focuses on the following areas of research: 1) identifying the molecular and cellular mechanisms responsible for the pathophysiology underlying fragile X syndrome, and 2) using non-viral vector to deliver Cas9 mRNA/sgRNA to develop potential therapeutics in mouse models for brain disorders. To address these questions, he uses molecular and cellular neurobiology tools, bioengineering and animal behavioral assays.

Eligibility: N/A

Mentor Name: Chung-Yueh (Jeremy) Lin
Mentor Role: Graduate student researcher
Principal Investigator: Takaki Komiyama
Institution: University of California, San Diego
Location: La Jolla, CA
Lab Website: https://komiyamalab.biosci.ucsd.edu/

Project Description: Investigating the inputs contributing to the potent, persistent value coding in RSC

Animals often encounter situations that require making decisions guided by their previous experiences to maximize the payout. This behavior involves multiple different kinds of information processing. Neural representations of choice, reward and action value have been observed in various brain regions, including the retrosplenial cortex (RSC), which receives inputs from many different brain regions. Whether these projections provide value information is unknown. Our lab will decode the neural activity of different axonal inputs in RSC by using two-photon microscopy to measure the calcium signals at the axon terminals. Both long-range inputs and inputs from nearby cortical regions will be examined. We hypothesize that different regions provide different value information to RSC (reward signals, updated chosen values, etc.). To evaluate their contribution to the value-based decision-making behavior, in a separate group of mice, our lab will inactivate a specific set of axons in RSC while monitoring their behavior. These experiments will give us substantial insight into the details of which inputs are critical for RSC to maintain value signals and whether local circuit motifs in RSC are required to persistently encode value information.

Mentor Biography: Chung-Yueh (Jeremy) Lin received his bachelor’s degree. in neuroscience and computer science at MIT. He is a rising fourth-year graduate student in the neuroscience graduate program at the University of California, San Diego (UCSD). He has been a member in Takaki Komiyama’s lab for two years, where he has been investigating how different cortical circuits support value-based decision making. As an undergraduate researcher at MIT, he worked with Harvey Lodish and Susumu Tonegawa. Lin has experience in system neuroscience, cell biology, and computational programming and modeling.

Eligibility: Students should not work over 19.5 hours per week as they are part-time employees.

Mentor Name: Bin Yu
Mentor Role: Graduate student researcher
Principal Investigator: Takaki Komiyama
Institution: University of California, San Diego
Location: La Jolla, CA
Lab Website: https://komiyamalab.biosci.ucsd.edu/

Project Description: Structural plasticity and neurogenesis during continual learning in the olfactory bulb

Although recent advances in artificial intelligence (AI) have led to a super-human performance in many tasks, the flexibility and adaptability of the human brain still far surpass AI. The brain can readily integrate experiences over many years and generate an adaptive network that performs various tasks flexibly, a process called continual learning. The olfactory bulb is a site of neurogenesis, the process of adding new neurons to an existing network in the adult mouse. Neurogenesis and structural plasticity — creating new synapses and erasing others — are involved in olfactory learning by restructuring the sparsely connected network composed of mitral and granule cells. These processes have yet to be well studied in AI but have the potential to enhance AI’s performance in continual learning settings. For this project, we will train mice to perform serial odor discrimination tasks and monitor the activity of olfactory bulb (OB) neurons longitudinally during learning to gain insights into how sensory circuits accommodate new learning without forgetting prior knowledge. These recordings will be complemented by manipulating specific circuit components using optogenetics and cell ablation experiments. These experiments could elucidate how brains outperform state-of-the-art neural networks in continual learning settings.

Mentor Biography: Bin Yu received his bachelor’s degree in electrical and computer engineering (ECE) from the University of Washington (UW) in 2015, and his master’s degree in ECE, under the mentorship ofJohn Tuthill, in 2017, also at UW. In addition, he has research experience in computer vision, data analysis, system neuroscience, and hardware design. In 2017, Yu became an ECE Ph.D. student at the University of California, San Diego (UCSD), with support from a UCSD ECE departmental fellowship. In 2018, he started working as a graduate student researcher in Takaki Komiyama’s lab at UCSD. He currently studies the roles of distinct cortical feedback and the function of neurogenesis in rodents’ olfactory bulbs while learning an olfactory perceptual task. His research is partially funded by Innovative Research Grants from the Kavli Institute For Brain and Mind at UCSD.

Eligibility: Students should not work over 19.5 hours per week as they are part-time employees.

Mentor Name: Daniela Seczon
Mentor Role: Graduate Student
Principal Investigator: Scott Murray
Institution: University of Washington
Location: Seattle, WA
Lab Website: https://courses.washington.edu/viscog/

Project Description: Neural differences of visual perception in autism

Our proposed project aims to investigate between-group differences in visual perception in relation to biological constructs using various research modalities, including EEG, MRI, eye-tracking and behavioral measures. The plentitude of data available offers numerous exciting research questions for a SURFiN fellow to explore.

Visual perception refers to our ability to perceive, interpret and respond to environmental stimuli. Studying visual perception in the context of psychopathology can provide a better understanding of specific cognitive and neural processes that differ in these conditions. In autism, visual perception differs in visual detection, motion perception and face processing tasks.

As a research assistant, the SURFiN fellow will gain valuable experience in research methods and techniques. They will have the opportunity to develop a variety of skills, including data analysis (which will include programming, although no prior experience is required), scientific reading, literature reviews and creating scientific poster presentations. This project is well-suitable for undergraduates with varying skill levels, including those with no prior research experience. Overall, we will work to tailor research goals that align with your interests and are most effective in helping you achieve long-term career goals.

Mentor Biography: Daniela (Dani) Seczon is a graduate student pursuing a Ph.D. in clinical psychology at the University of Washington (UW), where she is studying neural mechanisms of visual cognition of early visual processes in autism spectrum disorders under the supervision and mentorship of Scott Murray. Seczon earned her bachelor’s degree in both psychology and biochemistry from the University of Tulsa and a master’s degree in neuroscience and education from Teachers College, Columbia University.

Before arriving to UW, Seczon had previous research experience with EEG and eye-tracking experiments on topics such as perceptual organization, attention and implicit learning, and individual differences. She is currently interested in exploring the heterogeneity observed in the autistic population, with the aim of better understanding underlying mechanisms. This could help improve early intervention strategies for individuals on the spectrum. To explore these interests, she is part of Scott Murray’s lab, which is conducting a multimodal study employing EEG, structural and functional MRI, eye-tracking and psychophysics experiments to investigate differences in brain structure and activity in relation to behavior in autism.

Overall, Seczon recognizes the significant impact that graduate students can have on the undergraduate research experience and is eager to play a lead role.

Eligibility: Undergraduate students are limited to 19.5 hours per week of work across all student jobs at the University of Washington during the academic quarter.

Mentor Name: Katherine Perks
Mentor Role: Graduate Student
Principal Investigator: Amy Orsborn
Institution: University of Washington
Location: Seattle, WA
Lab Website: http://faculty.washington.edu/aorsborn/

Project Description: Our movements are controlled by a combination of predictive feedforward control and reactive feedback control. It is thought that people exert feedforward control by learning internal models of how objects or devices will respond when interacted with. For example, you likely have an internal model of how moving a computer mouse affects the cursor you see on the screen. This project asks how internal models are learned and how, once learned, they impact behavior. We explore these questions by studying non-human primates as they interact with a touchscreen tablet and learn to follow a moving target on the screen. This novel in-cage tracking task is designed to simultaneously separate feedforward and feedback control components during motor behavior so that we can study the formation of internal models. As part of our team, the SURFiN fellow will assist with designing and running in-cage experiments. They will also analyze the behavioral data collected and use control theory methods to quantify internal models (i.e., feedforward control). This project will provide training in both experimental and computational approaches in systems neuroscience, and novel ways to study learning.

Mentor Biography: Katherine Perks is a neuroscience graduate student in the Orsborn Lab at the University of Washington. Her work focuses on understanding how the brain learns new internal models or adapts existing models for effective sensorimotor control. She is currently implementing the tracking task described above in a brain-computer interface (BCI) paradigm to quantify internal models at the neural level. Perks received her bachelor’s degree. in neuroscience from the University of Texas at Austin, where she studied the molecular basis of motor disorders and potential cures using C. elegans. She also performed postbaccalaureate research at Baylor College of Medicine as an NIH PREP fellow.

Eligibility: Undergraduate students are limited to 19.5 hours per week of work across all student jobs at the University of Washington during the academic quarter.

Mentor Name: Vardan Arutiunian
Mentor Role: Postdoctoral Fellow
Principal Investigator: Sara Webb
Institution: Seattle Children’s Hospital/Seattle Children’s Research Institute
Location: Seattle, WA
Lab Website: http://depts.washington.edu/pbslab/wordpress/

Project Description: Although language impairment is not considered a core characteristic of autism , it is known that language and communication difficulties are among its earliest risk markers. Little is known about the early neurophysiological mechanisms of language as related to later autistic social attention and communication alterations. Specifically, we explore how different components of spectra (periodic, reflecting oscillatory part of the spectra; and aperiodic, reflecting arrhythmic component of neural field) may be altered in infants at elevated risk for autism using tasks that include natural language and communication. In this project, 30 typical likelihood infants and 247 infants at elevated risk for developing autism (due medical risk) are included. EEG was recorded at 6 and 12 months, with concurrent behavioral assessment of language and social communication. Autism behaviors are assessed at 24 and 36 months. During EEG recording, infants were presented with videos or live interaction that included naturalist infant directed language or a non-social non-linguistic condition. The main goals are to assess how different components of the spectra:1) relate to linguistic social attention, 2) change during the first year of life, 3) relate to concurrent language abilities, and 4) may predict language and social communication outcomes.

Mentor Biography: Vardan Arutiunian isa postdoctoral fellow in Sara Jane Webb’s lab at Seattle Children’s Research Institute. He received a Ph.D. in linguistics from the Center for Language and Brain at HSE University in Moscow, Russia in the field of language and communication in autism.In his research, Arutiunian uses behavioral assessment, genetic approaches and neurobiological methods (magnetoencephalography, electroencephalography, brain morphometry) to investigate variability of language skills as well as structural and functional brain mechanisms of language impairment in children with autism. He received a number of research and teaching awards from several organizations, including the European Union, and has published eight articles in international peer-reviewed journals.

Eligibility: N/A

Mentor Name: Fereshteh Lagzi
Mentor Role: Postdoctoral Fellow
Principal Investigator: Adrienne Fairhall
Institution: University of Washington
Location: Seattle, WA
Lab Website: https://fairhalllab.com/

Project Descriptions:

Project 1: Many events unfold over time and/or space, giving both experiences and outputs such as language, thoughts and motor activity a sequential structure. Sequential patterns in neural activity have been observed in multiple brain areas, but most notably in the hippocampus, an area involved in learning and memory, where they recur spontaneously following experience. The acquisition of sequences may therefore be a fundamental mechanism the brain uses to learn and store relationships. In this project, we will use modeling and simulations to explore different mechanisms for building neural sequences. Many current models assume that sequences are learned by synaptic plasticity, i.e., strengthening connections between neurons such that driving the first neuron to fire can activate the entire sequence. However, recent work has brought attention to the potential general importance of nonsynaptic plasticity mechanisms. We will explore how changes in intrinsic neuronal properties, such as excitability, as well as the non-random structure of the network can contribute to sequence generation, and how the resulting models differ from more traditional synaptic approaches. The results of this study will highlight the necessary components for the generation and maintenance of sequences in neuronal networks.

Project 2: Typically in neural networks, neurons are modeled as connected with chemical synapses, whereby signals are transmitted in an all or none thresholded fashion at precise times. When we train artificial neural networks, we generally assume that learning occurs through changes in synaptic weights. However, many biological systems have neural connectivities that are mediated also or instead by gap junctions, which couple neurons electrically, leading to a continuous sharing of electrical potential. The motif of gap junctional coupling is widespread throughout neural systems; intriguingly, particularly during early development in cortex, in regions that undergo neurogenesis, such as the birdsong circuit nucleus HVC and in the highly regenerative organism Hydra. What role might this coupling play? We hypothesize that gap junctional coupling provides a mechanism for neurons to form initial connectivity, bringing new neurons into a coupled relationship, that may subsequently be refined by synaptic plasticity. In this project we will explore this idea using modeling of Hydra and of HVC, where well-defined activity patterns (global repetitive firing of subnetworks and precise temporal sequences) have been well studied.

Mentor Biography: Fereshteh Lagzi is a postdoctoral fellow in the Department of Physiology and Biophysics at the University of Washington (UW). She has a background in computational neuroscience, nonlinear dynamics and control theory. During her graduate research., Lagzi studied the dynamics of competition and cooperation in spiking networks of interacting subnetworks, and their bifurcation. After completing her Ph.D., she studied artificial neural networks and analyzed different recurrent networks from a dynamical system point of view. In her postdoctoral research, she studied assembly formation considering cell-specific plasticity mechanisms for different inhibitory subtypes and their interaction with excitatory Hebbian learning mechanisms. Her studies link rate and weight dynamics in spiking networks in an interesting low-dimensional framework. Lagzi received the competitive Swartz Foundation Postdoctoral Fellowship in computational neuroscience and joined the Fairhall Lab in 2021. Currently, Lagzi studies circuit dynamics underlying sequence generation and maintenance. More precisely, she is interested in understanding the role of sequences in learning. Also, the dynamics and emergence of cell assemblies mediated by inhibitory subtypes are an active area of her research. Lagzi also considers alternative mechanisms to synaptic plasticity that can modify circuit dynamics and guide learning.

Eligibility: Undergraduate students are limited to 19.5 hours per week of work across all student jobs at the University of Washington during the academic quarter.

Mentor Name: Daniel Birman
Mentor Role: Postdoctoral Fellow
Principal Investigator: Nicholas Steinmetz
Institution: University of Washington
Location: Seattle, WA
Lab Website: www.steinmetzlab.net

Project Description: Neuroscience lacks tools for easily displaying and exploring neural data in its original anatomical context. In this project, our group will continue expanding the capabilities of Urchin, a browser-based interactive 3D rendering tool. Urchin allows users to project their electrophysiology data into a 3D scene and explore it alongside the 3D anatomy of the mouse brain. The next step in Urchin’s development is to support the simultaneous electrophysiology and calcium imaging experiments that we perform in the lab. As part of the team, the SURFiN fellow will develop a calcium imaging visualization feature that projects video data back onto the 3D surface of the mouse brain. With the new multi-modal features working, we will use the upgraded renderer to develop a virtual reality experience allowing users to explore the correlations between electrophysiology and calcium imaging datasets. This project is ideal for someone with some programming experience and an interest in developing applied research tools for neuroscience.

Mentor Biography: Daniel Birman is a postdoctoral fellow leading the Virtual Brain Lab (VBL) project in the Steinmetz Lab at the University of Washington. He received his bachelor’s degree in biology from Cornell University in 2012 and his doctorate in cognitive neuroscience from Stanford University in 2019. His research interests range from studying visual attention using computational models based on electrophysiology and neuroimaging data to developing interactive 3D visualization tools for neuroscience. Birman currently leads the VBL project, developing browser-based visualization tools for experimental planning, data visualization and education and outreach. These tools are a step change in the ease-of-use and power of research tools developed for rodent electrophysiology and are in active use by dozens of neuroscience labs around the world. His ongoing research program aims to expand these tools to other domains and accelerate the speed at which large-scale neuroscience experiments can be performed. As the lead researcher on the VBL, Birman mentors a group of undergraduate students developing new features for the VBL tools. In addition to receiving a Washington Research Foundation Fellowship in 2020 to support his postdoctoral research, he received Stanford’s most prestigious teaching honor in 2018 for his efforts mentoring graduate and undergraduate teaching assistants while modernizing an introductory neuroscience course.

Eligibility: Undergraduate students are limited to 19.5 hours per week of work across all student jobs at the University of Washington during the academic quarter.

Mentor Name: Anthony Fischer
Mentor Role: Postdoctoral Researcher
Principal Investigator: Joseph Dougherty
Institution: Washington University in St. Louis
Location: St. Louis, MO
Lab Website: http://genetics.wustl.edu/jdlab/

Project Description: Non-coding mutations are an under-researched area in disease presentation and progression. The non-coding areas of brain-derived messenger RNA (mRNA) are critical for translation initiation, mRNA lifespan and even localization in neurons. Recently, clinicians at our institution have identified 3’ untranslated region (UTR) mutations in a patient family with neurodevelopmental disorder (NDD) that alter mRNA expression profiles and segregate well with the NDD phenotype. Specifically, two affected sons and a maternal uncle all carry the mutation and express the phenotype, while the mother is an unaffected carrier. This suggests the allele interacts with sex to produce the phenotype. The goal of this study is to determine the mechanism of action of this expression difference, validate these findings with protein expression assays, and test whether this effect interacts with sex.

This opportunity will give the SURFiN fellow an opportunity to think critically about all aspects of study. Work done in a research lab can feel disconnected at times for undergraduates if they are not actively involved in every step. The fellow will be involved at each step, including review of the literature, review of initial data, aspects that need further investigation/mechanisms to be uncovered, experimental design with proper controls, data analysis and presentation of findings.

Mentor Biography: Anthony Fischer is a skilled and dedicated researcher in the field of molecular biology. He graduated from the University of Missouri-St. Louis (UMSL) in 2018 with a degree in biology, where he developed a strong interest in post-transcriptional gene regulation.

During his time at UMSL, he conducted research on the regulation of mRNA decay through the binding of Pumilio proteins to the 3’UTR region of mRNA molecules, and the implications this had on nutrient sensing and ribosome synthesis. This work involved a combination of experimental techniques, including protein-protein interaction assays, RNA quantification, cell culture and fluorescence microscopy.

After graduation he briefly began postdoctoral research on molecular mechanisms of colorectal cancer before transitioning into studying autism-associated de novo non-coding variants. His current work seeks to adapt current massively parallel reporter assay (MPRA) technology to delineate at which part in an mRNA’s lifecycle the variants are exerting their influence.
Beyond his own research, he is committed to sharing his knowledge and expertise with others. He has mentored several undergraduate and graduate students since the start of his science career, helping them to develop their research skills and contributing to the next generation of scientists.

Eligibility: N/A

Mentor Name: Colin Florian
Mentor Role: Graduate Student
Principal Investigator: Joseph Dougherty
Institution: Washington University in St. Louis
Location: St. Louis, MO
Lab Website: http://genetics.wustl.edu/jdlab/

Project Description: Mutations in the gene myelin transcription factor 1-like (MYT1L) are associated with neurodevelopmental disorders and autism. It is an integral component for the generation of mature and functional neurons in vivo (see Chen et al., 2021; Wöhr et al., 2022). Furthermore, MYT1L loss of function mice show a sex x genotype interaction in transcriptional and behavioral responses (see Chen et al., 2021).

This project will specifically focus on transcription regulation by MYT1L. It is unknown why losing one copy of MYT1L results in disorder. This result suggest the hypothesis that MYT1L’s function in gene regulation depends on its level. Therefore, the SURFiN fellow will generate select MYT1L reporter constructs using a new cloning strategy being implemented in our lab. (This strategy will allow for inclusion of larger regulatory elements for reporter libraries which is traditionally restricted by synthesis and will benefit our lab as a whole). Several quality control checks provide data visualization for immediate confirmation and feedback of success. Once generated, these reporters will be functionally validated and tested in cell culture models. The fellow will then test the role of different levels of MYT1L protein on regulating gene expression using these reporters.

In summary, this project will provide the fellow with training and experience in literature review, molecular biology and tissue culture techniques, and data analysis with several checkpoints to provide affirmation and feedback.

Mentor Biography: Colin Florian began their scientific career in 2014 when they became employed at the Genome Engineering and iPSC Center (GEiC) at Washington University in St. Louis. The focus of the GEiC is to generate genetically modified cell lines and animal models using the CRISPR-Cas9 system. In their time as a technician at the GEiC, they were able to master many molecular biology and tissue culture techniques as well as gaining computational experience. Additionally, they trained and mentored several new members of the team throughout my time spent at the GEiC.

Currently, Florian is a third-year molecular genetics and genomics graduate student in the lab of Joseph Dougherty at Washington University in St. Louis. Their research is focused on understanding how sequence composition influences transcription at genomic targets bound by Mmelin transcription factor 1-like (MYT1L), which is associated with neurodevelopmental disorders and autism when loss of function mutations are present. To address this question, they will be employing Massively Parallel Reporter Assays (MPRA) to test a multitude of MYT1L promoter targets. Through this research, Florian hopes to be able to identify and characterize mechanisms through which MYT1L functions to produce a transcriptional response.

Eligibility: N/A

Mentor Name: Sriram Jayabal
Mentor Role: Basic Life Research Scientist
Principal Investigator: Jennifer Raymond
Institution: Stanford University
Location: Palo Alto, CA
Lab Website: https://raymondlab.stanford.edu/

Project Descriptions:

Project 1: Neurobiological underpinnings of meta-learning

Meta-learning, an old concept in psychology, is the ability of humans to improve the way they learn with experience. Our previous experience of learning a skill makes us better at learning another, related skill. For instance, an athlete will learn a new sport faster than someone without the same level of experience in similar learning tasks. How does the brain accomplish this powerful process of learning to learn? Even though much progress has been made in understanding the neural mechanisms of learning, the neural mechanisms of meta-learning are still an enigma. This research will address this important gap in our knowledge of brain function. Specifically, the main goal is to develop a behavioral paradigm in mice which will assess meta-learning by using well understood oculomotor learning as a model system.

Project 2: Assessing the role of cerebellum in adaptive oculomotor integration

Neural integrators are networks of neurons that perform the mathematical integral of a signal that varies over time, enabling neurons to compute and store information over different timescales. One of the most well studied neural integrators is the oculomotor integrator, first discovered in the 1960s, which holds the gaze steady when the eyes are turned away from the null position. However, the precise role of cerebellum in oculomotor integration is still an enigma. This project will use mouse models and transgenics to first investigate how the properties of the oculomotor integrator are adaptively modified by experience. Then, using optogenetics, the role of cerebellar Purkinje cells, the sole output neurons of the cerebellar cortex, in adaptive neural integration will be characterized. The SURFiN fellow will thus contribute to all aspects of the research from hypothesis formation and testing, experimental design, data collection and analysis, graphing and scientific communication.

Mentor Biography: Sriram Jayabal is a basic life research scientist in neurobiology at the Stanford University School of Medicine under the supervision of Jennifer Raymond. Before assuming his current role in October 2022, Jayabal was a postdoctoral fellow in the same lab from October of 2017 to September of 2022. He received his bachelor’s degree in biotechnology in India and moved to McGill University in Canada for his graduate study. At McGill, he studied the cerebellar pathophysiology that underlies the manifestation and progression of spinocerebellar ataxia type 6 under the supervision of Alanna Watt. Fascinated with the cerebellum, a region which is now known to play diverse functional roles, he moved to the Raymond Lab at Stanford to study how cerebellum implements learning. Specifically, he is exploring the neurobiological underpinnings of meta-learning (the ability to learn to learn) at the molecular, cellular and systems level by taking advantage of the experimentally and analytically tractable oculomotor cerebellum in healthy and disease animal models. He has trained about 23 students, including undergraduate, graduate and life science research personnel. He has also won the Stanford Bio-X Star Mentor Award.

Eligibility: N/A

Mentor Name: Amin Shakhawat
Mentor Role: Basic Life Research Scientist
Principal Investigator: Jennifer Raymond
Institution: Stanford University
Location: Palo Alto, CA
Lab Website: https://raymondlab.stanford.edu/

Project Description: This project investigates distributed plasticity in the cerebellum and related oculomotor circuitry during motor learning that alters the way the circuit computes. The SURFiN fellow will have the opportunity to utilize optogenetic perturbation of a synaptic plasticity mechanism combined with targeted optogenetic stimulation in vivo to dissect the algorithm governing the distribution of plasticity across sites in the circuit. The selected candidate will receive extensive training to contribute to this project by collecting and analyzing data, designing follow-up experiments and presenting research findings to multiple scientific communities.

Mentor Biography: Amin Shakhawat is a Basic Life Research Scientist in neurobiology at the Stanford University School of Medicine. He completed his doctoral research at Memorial University of Newfoundland inCanada with Qi Yuan. His graduate research demonstrated how the locus coeruleus, the major noradrenergic nucleus of the brain, facilitates reward-related odor engram formation in the olfactory bulb and in the piriform cortex. For this project, he employed a molecular imaging technique called Arc catFISH that captures the activity patterns of hundreds of neurons at two different time points. Using this technique, he studied neural dynamics of a rewarded odor engram in the olfactory system in both five-to-six-day old rat pups and adult rats. Shakhawat’s postdoctoral research at Stanford focuses on elucidating the algorithm that a neural circuit uses to determine which synapses, among a sea of recently active synapses, should be modified to implement learning.

Eligibility: N/A

Mentor Name: Yimei Cai
Mentor Role: Graduate Student
Principal Investigator: Tingting Wang
Institution: Georgetown University
Location: Washington, D.C.
Lab Website: https://www.wangtingtinglab.org/

Project Description: A large number of autism risk genes encode chromatin remodeling proteins, including chromodomain helicase DNA-binding protein (CHD) family genes CHD2 and CHD8. Although epigenetic mechanisms are critical for neural differentiation and learning/memory, little is known about how chromatin remodeling proteins affect brain function in a cell type-specific manner. We recently discovered that neuronal and non-neuronal CHD1, the Drosophila homologue of mammalian CHD2, plays distinct roles in regulating synaptic physiology during the induction and maintenance phase of homeostatic plasticity. However, how CHD1 expressed in different cell types contributes to the behavioral deficits in autism at the synaptic and circuit levels remains to be elucidated.

In this project, we propose to investigate the cell type-specific roles of CHD1 in regulating seizure behavior, circadian rhythm and sleep in Drosophila models. First, we will study seizure behavior, circadian rhythm and sleep in a Drosophila CHD1 genetic loss-of-function mutant. Nextwe will investigate the cell type-specific function (neuron, muscles and glia) of CHD1 in regulating different behaviors, using RNAi and tissue-specific rescue strategies. Finally, we will assess neuronal and glial calcium signals in the CHD1 mutant using genetically encoded calcium sensors and confocal calcium imaging method.

Mentor Biography: Yimei Cai is a third-year Ph.D. student in the Department of Pharmacology and Physiology at Georgetown University. Unlike many other researchers in the field, Cai’s journey started with a teaching career. With a master’s degree in education, she taught biology for two years in local public high schools, focusing on special education. While teaching, Cai developed interests in neurodevelopmental disorders during her interactions with special needs students. After receiving her master’s degree in pharmacology, she was accepted into the Ph.D. program in pharmacology and physiology at Georgetown University.

At Georgetown, Tingting Wang’s lab uses Drosophila and mammalian models to investigate the molecular and cellular basis of homeostatic signaling in health and disease. The lab has identified several genes that are essential for glial-neuron communications in homeostatic synaptic plasticity. One of the genes identified is chromodomain helicase DNA-binding protein 2 (CHD2), which is linked to the risk of epilepsy, intellectual disability and autism. In the Wang Lab, Cai is particularly interested in the mechanisms that underlie the behavioral deficits in CHD2 mutants. She is investigating the function of Drosophila homologue of CHD2 in synapse development, synaptic plasticity, seizure behavior and sleep. Recently, Cai was selected for the prestigious Cosmos Scholars Grant program.

Eligibility: N/A

Mentor Name: Shannon Cahalan
Mentor Role: Graduate Student
Principal Investigator: Gabriela Rosenblau
Institution: George Washington University
Location: Washington, D.C.
Lab Website: dsnlab.org

Project Description: The proposed project for the SURFiN fellow at George Washington University (GW) will be situated within a larger NIH funded project on social and non-social learning in autism. Being part of this project will afford unique opportunities such as learning to administer clinical and behavioral measures as well as running functional magnetic resonance imaging (fMRI) visits and analyzing and presenting these data. The fellow will also have the opportunity to participate in trainings on neuropsychological assessments by our licensed clinical psychologist from Children’s National Hospital.

Within the larger study, the fellow’s specific project will examine individual differences and developmental changes in social learning across autistic and typically developing adolescents (aged 8-17 years old). By the start date, we expect to have successfully collected at least 30 fMRI data sets and data collection will be ongoing during their fellowship. Under the close mentorship of Shannon Cahalan, the graduate student overseeing the larger project, and with additional supervision of principal investigator Gabriela Rosenblau, the fellow will train in collecting, preprocessing and analyzing fMRI data. They will investigate how individual differences in social learning and their neural underpinnings are modulated by age, participants’ cognitive skills (measured with neuropsychological batteries) and social skills (measured with parent-report questionnaires). Fellows will be exposed to fMRI data collection with minors, state-of-the art neuroimaging analyses pipelines such as the fMRIprep preprocessing pipelines, hands-on training in statistical analysis and the efficient presentation of scientific results in a poster presentation. Fellows will acquire technical skills such as working with Python and Matlab scripts and they will be provided the opportunity to present study results at a GW-organized student conference and at an international conference, such as the Society for Neuroscience annual meeting.

Mentor Biography: Shannon Cahalan received bachelor’s degrees in brain and cognitive sciences and psychology at the University of Rochester in 2019. Following her bachelor’s degree, she spent two years working as a lab coordinator for the Mathematics, Reasoning and Learning Lab and the Language, Behavior and Brain Imaging Lab at Rutgers University-Newark. At Rutgers, she studied the neural underpinnings of reading differences in autism. Additionally, she spent several months working as a research assistant at the Kessler Foundation’s Center for Traumatic Brain Injury Research. Cahalan’s Ph.D. project is focused on social and non-social learning in autism. She is using functional neuroimaging and computational modeling to examine social and non-social learning in autism and is especially interested in studying gender differences in autism. Her position is funded by the NIH project on social and non-social learning. As such, she is overseeing the larger project goals, as well as training and mentoring fellow research assistants and undergraduate student interns in the lab on a variety of tasks including neuropsychological testing and fMRI data analysis.

Eligibility: N/A

Mentor Name: Ourania Semelidou
Mentor Role: Postdoctoral Researcher
Principal Investigator: Andreas Frick
Institution: Institut National de la Sante et de la Recherche Medicale, ADR-Bordeaux
Location: Bordeaux, France
Lab Website: https://neurocentre-magendie.fr/recherche/Frick/descriptionTeam.php

Project Description: Exploration of altered tactile perception in a mouse model of autism using a translatable approach

Altered sensory experience is one of the core features of autism, a neurodevelopmental condition characterized by alterations in social communication and repetitive behaviors. Altered sensitivity and reactivity to sensory stimulation affect 90 percent of autistic individuals, having a strong impact on their day-to-day life and contributing to the development of higher cognitive symptoms and repetitive behaviors. Importantly, these simple sensory alterations can be exploited to identify the neurobiological mechanisms of autism.

In this project, our lab aims to explore the neurobiological mechanisms that underlie altered tactile perception in autism. To this end, we use a sophisticated toolset, combining a novel behavioral task with in vivo two-photon microscopy in a genetic mouse model of autism. To assess tactile sensitivity we developed a perceptual decision-making task, where the animal reports the presence of vibrotactile stimuli of different intensities to receive a water reward. In parallel, we measure neuronal activity at cellular resolution, focusing on the excitatory and inhibitory neurons of the somatosensory cortex. The results of this project we help us understand how tactile responses are changed in autism and identify their neocortical underpinnings, aiming to establish preclinical biomarkers to test treatments for autism.

Mentor Biography: Ourania Semelidou is a postdoctoral researcher in neuroscience at the Neurocentre Magendie, Bordeaux, France. She obtained her bachelor’s degree in molecular biology and genetics at the Democritus University of Thrace in Komotini, Greece, and continued with a master’s degree in molecular medicine and neuroscience at the National and Kapodistrian University of Athens. She obtained a doctorate in neuroscience from the University of Crete. Semelidou’s research is focusing on better understanding altered sensory experience in autism. She is interested in perception and decision-making and in her current project she aims to characterize perceptual measures of atypical tactile and multisensory information processing and to uncover their neural underpinnings in genetic mouse models of autism. Throughout her research career, Semelidou has received several honors and awards, including a postdoctoral fellowship for three years from the Fondation pour la Recherche Médicale (FRM), awarded in 2020, and in 2022 received a mobility project funding from the GIS Autisme et TND, the autism and neurodevelopmental disorders scientific interest group that is supported by the French National Strategy for Autism. In addition, in 2018 she was selected as one of the most qualified young scientists to participate in the 68th Lindau Nobel Laureate Meeting, dedicated to the physiology or medicine prize.

Eligibility: N/A

Mentor Name: Yukti Vyas
Mentor Role: Postdoctoral Research Fellow
Principal Investigator: Andreas Frick
Institution: Institut National de la Sante et de la Recherche Medicale, ADR-Bordeaux
Location: Bordeaux, France
Lab Website: https://neurocentre-magendie.fr/recherche/Frick/descriptionTeam.php

Project Description: Exploring neocortical alterations in rodent models and human iPSC-derived neurons in autism

Autism is a multifactorial neurodevelopmental condition characterized by deficits in social communication and repetitive or restrictive behaviors. Atypical sensory experience affects 90 percent of autistic individuals. In this project, we will explore the neurophysiological basis of tactile sensory abnormalities in autism, extrapolating alterations in neuronal excitability at the single cell level, and examining the influence of these changes at the behavioral level. This will be done using well-characterized rodent models of autism and a multitude of techniques including ex vivo and in vivo whole-cell patch-clamp electrophysiology, immunohistochemistry and fluorescence microscopy for neural reconstruction and morphological examination of neuronal processes, and an array of behavioral tests evaluating sensory abnormalities in autism models. Furthermore, to translate the findings from rodent models to preclinical human models, we will investigate alterations in induced pluripotent stem cell (iPSC)-derived human cortical neurons from patients with idiopathic autism and CRISPR-induced autism mutation. In parallel, we will investigate the therapeutic potential of our mechanism-based targets. Along with gaining hands-on experience in these neuroscientific techniques, the student will gain exposure to the process of culturing human neurons, and learn methods to analyze and quantify their experimental data.

Mentor Biography: With over ten years of research experience and a Ph.D. in neuroscience, Yukti Vyas is a postdoctoral research fellow at the Neurocentre Magendie in Bordeaux, France, with a deep interest in studying preclinical models of neurodevelopmental disorders from the cellular to the behavioral level. She is an expert electrophysiologist, behavioral scientist and cell culture specialist, using these techniques to understand the functional nuances of the brain in physiological and pathological conditions. Her research and wider interdisciplinary collaborations have resulted in high-quality publications in neurodevelopment and therapeutic research. Her scientific contributions and presentations have led to prestigious and competitive national awards, including the Mary Bullivant Prize in Physiology, the Physiological Society of New Zealand John Hubbard Prize, and the Kate Edger Educational Charitable Trust Dame Dorothy Winstone Doctoral Award. In addition, she has an aptitude for mentoring graduate students. She has supervised four graduate student projects from start to finish, teaching complex neuroscientific techniques and providing scientific and intellectual support, with the aim to develop them into independent, confident young scientists. She has also taught doctoral and postdoctoral students at the CAJAL Advanced Neuroscience Training Programme and the Australian Course in Advanced Neuroscience, and hundreds of undergraduates in physiology and anatomy courses.

Eligibility: N/A

Mentor Name: Théo Gauvrit
Mentor Role: Graduate Student
Principal Investigator: Andreas Frick
Institution: Institut National de la Sante et de la Recherche Medicale, ADR-Bordeaux
Location: Bordeaux France
Lab Website: https://neurocentre-magendie.fr/recherche/Frick/descriptionTeam.php

Project Description: Machine learning tools to explore atypical sensory information processing in autism mouse models

Sensory alterations were recently added as one of the core features of autism. These sensory characteristics can be exploited to better understand the neurobiological mechanisms of autism and to decipher atypical neuronal computing in autism. Preclinical models of autism allow us to study neuronal activity underlying sensory processing by employing state-of-the-art techniques like calcium imaging and combining them with behavioral tasks.

This project aims to explore atypical sensory perception in autism, focusing on neuronal population dynamics. We will employ machine learning tools to analyze complex multidimensional data obtained by combining calcium imaging in the somatosensory cortex with a perceptual decision-making task. The development of different pipelines in Python will allow the detailed exploration of neuronal activity during two fundamental phases of perception: the encoding of the stimulus and the decision-making (response) of the mouse. In addition, these results will permit us to test our previous hypothesis on increased neuronal noise and network imbalance in autism. This project will be the first step to the construction of a Generalized Linear Models (GLM) that will allow us to tackle the different dynamic components of neuronal activity involved in atypical sensory processing in different mouse models of autism.

Mentor Biography: Théo Gauvrit is a graduate student at the University of Bordeaux, in the lab of Andreas Frick at the Neurocentre Magendie in Bordeaux, France. He first joined the team in February of 2020 for his master thesis in bioinformatics, during which he developed tools for the analysis of electrophysiological data to characterize atypical sensory information processing in the Fmr1KO mouse model of autism. He continued his work in the lab as a doctoral candidate, studying the role of neuronal noise and network states in the generation of sensory response variability. He is interested in better understanding the role of neuronal noise in atypical sensory processing in autism and exploring this feature as a translational biomarker of autism and a targetable mechanism for drug development. Based on his results from the analysis of single neuron recordings, he is now aiming to investigate the impact of noise and neuronal variability on neocortical processing at the neuronal population level. To this end, he is closely collaborating with experimental neuroscientists to analyze neuronal population activity from calcium imaging and multielectrode recordings. He is also aiming to obtain a model of circuit function using machine learning, in order to tackle the different dynamic components of neuronal activity involved in atypical sensory information processing in different mouse models of autism.

Eligibility: N/A

Mentor Name: Maria Gueidão Costa
Mentor Role: Graduate student
Principal Investigator: Andreas Frick
Institution: Institut National de la Sante et de la Recherche Medicale, ADR-Bordeaux
Location: Bordeaux France
Lab Website: https://neurocentre-magendie.fr/recherche/Frick/descriptionTeam.php

Project Description: Perceptual decision-making as a marker of atypical sensory experience in genetic mouse models of autism

Atypical sensory experience affects approximately 90 percent of individuals with autism and has been recently considered a core feature of autism according to diagnostic criteria of the 5th edition of Diagnostic and Statistical Manual of Mental Disorders. Abnormal auditory perception is well documented in autism, generally including alterations in pitch perception, poor sound discrimination, increased sensitivity to loud noises, reduced auditory stimuli habituation and difficulty filtering sound in a noisy background. These features exert a significantly negative impact on social engagement, communication and learning. Recent evidence suggests that neurobiological changes associated with atypical sensory experience can manifest not only in peripheral circuits and primary sensory cortices, but also in brain regions important for top-down control of sensory information processing such as the prefrontal cortex. Our main goal is to identify auditory perceptual biomarkers for autism and investigate their underlying neurobiological mechanisms in genetic mouse models of autism. To address this we combine a sensory-based decision-making task designed to characterize auditory processing, with in vivo calcium imaging of prefrontal neuronal activity in freely moving animals. The objective is to identify circuit alterations impacting top-down control of sensory perception and, ultimately, to use these alterations as biomarkers to evaluate pharmacological therapy.

Mentor Biography: Maria Gueidão Costa is a graduate student in neuroscience at the Neurocentre Magendie in Bordeaux, France. She obtained her bachelor’s degree from the School of Health of the Polytechnic Institute of Porto in Portugal, followed by a master’s degree in cellular and molecular biology with specialization in neurobiology at the Faculty of Science and Technology of the University of Coimbra, also in Portugal. During this period Costa received an Erasmus+ scholarship for a three-month internship in Trieste, Italy, as a bachelor’s student, and an Erasmus+ scholarship for an eleven-month internship at the Neurocentre Magendie to work on her master’s research project. In 2021, she was selected for a four-year doctoral fellowship from the University of the Basque Country in Spain and she enrolled in the international doctoral program in neuroscience in cotutelle agreement between the University of the Basque Country and the University of Bordeaux. Costa is particularly interested in identifying the prefrontal neural circuits that are recruited during decision-making. Her current research project aims to characterize altered sensory perception in autism and explore its neural underpinnings in the prefrontal cortex.

Eligibility: N/A

Mentor Name: Senka Hadzibegovic
Mentor Role: Postdoctoral Researcher
Principal Investigator: Andreas Frick
Institution: Institut National de la Sante et de la Recherche Medicale, ADR-Bordeaux
Location: Bordeaux France
Lab Website: https://neurocentre-magendie.fr/recherche/Frick/descriptionTeam.php

Project Description: Changes in intrinsic excitability of prefrontal cortex underlie early cognitive impairment in Alzheimer`s disease

Rapid forgetting is an early symptom of Alzheimer`s disease (AD) that correlates with amyloid-ß accumulation in the prefrontal cortex (PFC). Data from our group show that associative learning tasks recruit specific PFC neuron populations and trigger plasticity in the intrinsic excitability/ion channels of these neurons as crucial cellular mechanism of long-term memory storage. We also found that amyloid-ß alters the function of these ion channels in PFC neurons. We hypothesize that abnormal excitability causes dysfunction of PFC network activity and crucial cellular memory mechanisms, resulting in a disruption of long-term memory storage and thus faster forgetting. The overall goal of our proposal is to characterize the impact of amyloid-ß on the activity of PFC neuronal ensembles at cellular resolution during different phases of memory formation. Further, we want to probe the consequences of modulating the excitability of PFC engram neurons for correcting deficits in memory performance, as well as network activity. These neuronal activity measures will enable us to evaluate therapeutic strategies targeting ion channels as promising therapeutic targets in early-phase AD. We will use a highly innovative approach combining associative memory tasks with novel viral tool-based approaches, transgenic mice, electrophysiology, and qPCR approaches.

Mentor Biography: After acquiring a diploma as biological pharmacist from the Belgrade University in Serbia, Senka Hadzibegovic obtained an Erasmus Mundus fellowship to join the neuroscience community in Bordeaux,France to pursuit her Ph.D. During her doctoral studies, under the supervision of Bruno Bontempi from the Institute of Neurodegenerative Diseases (IMN) in Bordeaux, she used different approaches, ranging from behavioral to molecular analysis in a mouse model of Alzheimer’s disease (AD) to identify new markers of AD. Her work pointed to a crucial involvement of hippocampal oscillations called sharp-wave ripples in spatial memory formation and identified amyloid-β induced impairment in dynamics of these ripples as a mechanism responsible for the spatial memory deficits associated with AD. At the molecular level she was successful in establishing that amyloid-β destabilizes synaptic organization and increases an extrasynaptic pool of GluN2B-containing NMDA receptors, a reorganization that translates into impaired memory formation. She presented her work at international conferences obtaining awards for best poster and presentation. As a postdoctoral researcher in the Frick Lab in Bordeaux, she has been studying the neuronal allocation mechanisms of remote memories in under physiological conditions and in two mouse models of AD. Thus, an important driving force of her research is to understand the molecular and cellular processes underlying memory formation and to identify changes that can explain memory deficits associated with AD.

Eligibility: N/A

Mentor Name: Joaquin Rapela
Mentor Role: Research Engineer Fellow
Principal Investigator: Maneesh Sahani
Institution: University College London
Location: London, United Kingdom
Lab Website: https://www.ucl.ac.uk/gatsby/gatsby-computational-neuroscience-unit

Project Description: Understanding neural data with advanced statistical methods

This project will focus on a collaboration that aims to understanding how mice forage in naturalistic environments. Rapela is using advanced statistical methods to infer properties of this behavior and neural activity. On a related collaboration, we are working with the author of Bonsai, an outstanding software for the control of neuroscience experiments, to incorporate into it advanced machine learning methods that will enable a new generation of neuroscience experiments.

This project will provide a SURFiN fellow broad training on beautiful experimental and computational neuroscience topics. The fellow will acquire practical experience on the application of these topics by contributing to any of the above collaborations.

The student will benefit by being part of our world-class computational and experimental institutions, and this research experience could well position them to pursue graduate studies in either field.

This project will best fit a student with quantitative background (e.g., linear algebra, probability), good programming experience (e.g., Python), and an interest in using these skills to understand nature (e.g., brain function).

Mentor Biography: Joaquin Rapela received his bachelor’s degree in computer science and his doctorate in signal processing from the University of Southern California. He did postdoctoral training at University of California, San Diego, and at Brown University in statistical neuroscience topics. In his work, he develops and applies advanced statistical method to understand the function of the brain. Currently, he is a research engineer fellow at the Gatsby Computational Neuroscience Unit (GCNU), where he distributes advanced statistical methods developed at the unit and builds collaborative projects with scientists at the Sainsbury Wellcome Center (SWC).

Eligibility: N/A

Mentor Name: Charlie Fieseler and Itamar Lev
Mentor Role: Postdoctoral Researchers
Principal Investigator: Manuel Zimmer
Institution: University of Vienna
Location: Vienna, Austria
Lab Website: https://neurodevbio.univie.ac.at/zimmer-research/

Project Description: What is the neuronal representation of brain states?

The Zimmer Lab at the University of Vienna, Austria, utilizes the microscopic roundworm C. elegans as a model organism to explore fundamental questions in neuroscience. With only 302 neurons in its nervous system, we can identify each neuron and leverage a synaptic resolution connectome to understand the network’s architecture. Our lab has developed novel technologies to record the activity of all neurons in the worm’s brain while it freely crawls under a microscope. Additionally, we employ advanced AI techniques, such as convolutional neuronal networks, to extract meaningful information from these experiments.

This SURFiN project aims to investigate how longer-lasting behavioral states, including sleep, arousal, hunger and satiety, are encoded in the brain. The project will entail conducting behavioral and neuronal imaging experiments on animals that switch between these states. The fellow will work with two mentors, with each experimental and computational background, to develop a pipeline that can quantitatively describe such brain states in complex datasets.

We therefore are seeking students interested in combining experimental and computational work. This unique opportunity will provide an excellent learning experience in both fields while working on a project at the forefront of neuroscience research.

Charlie Fieseler Biography: Charlie Fieseler started their academic journey interested in physics and, like many of their peers, was impressed by compact theories like general relativity. They continued to work in condensed matter theory, but realized that such strongly interacting systems are extremely complex and messy. Then, after graduating from university in the U.S., they taught high school in Japan. Experiencing a less academic and human-oriented side of the world continued their trajectory into their current and more interdisciplinary field: computational neuroscience. In addition, they feel that this experience of full time teaching has been invaluable to all subsequent teaching duties.

In their current position as a postdoctoral researcher, Fieseler fully managed a cohort of five undergraduate students on a computational project and supervised a partial masters thesis. They fundamentally believe that science is a social endeavor, and that its continued success requires support at all levels: educational, intellectual and social. They have put this into action by listening to the interests and plans of the students mentioned above, and supporting them in getting additional position in our lab or elsewhere. Fieseler hopes to both use the skills they already have and continue to grow as a mentor through the SURFiN program.

Itamar Lev Biography: Itamar Lev is currently a postdoctoral researcher in the Zimmer Lab at the University of Vienna, investigating C. elegans neuroscience. They completed their Ph.D. at Tel Aviv University, where they worked on transgenerational inheritance via heritable small-RNAs in C. elegans. Currently, they study how distributed brain states convey feedback on behavior execution, and how these behaviors are flexibly adjusted in varying environments. Lev’s research leverages novel and unique techniques such as functional whole-brain imaging in freely behaving animals. A special interest of their work is to study neuronal responses in natural, ecologically relevant settings, such as when the worms interact with their predator, a nematophagic fungus. Their research is funded by the VIP2, EMBO and now HFSP postdoctoral fellowships.

Eligibility: N/A

Mentor Name: Leiron Ferrarese
Mentor Role: Postdoctoral Fellow
Principal Investigator: Hiroki Asari
Institution: European Molecular Biology Laboratory
Location: Rome, Italy
Lab Website: https://www.embl.org/groups/asari/

Project Description: Brains have evolved to interpret the environment and provide a motor output that best fits for survival. Autistic individuals often have abnormal interpretations of the environment hence behave differently, but how is the autistic brain different from the healthy one? In our lab, we study anomalous neuronal dynamics occurring in the brains of autism model mice to gain insights into how this disorder can arise and how it can be treated. We recently found a suboptimal neuronal computation in the early visual system of autism model mice when aversive visual stimuli were presented under different environmental contexts. Here we propose to expand on these results with a behavioral characterization. Specifically, we will first perform behavioral assays to monitor the responses to visual threats, and use machine learning tools to quantify and compare the responses between healthy and autism model mice. Such experiments will also be combined with histological assays and neurophysiological recordings to better understand the relationship between the behavior and the brain structure and function. Candidates can have a background from either natural science such as biology and physics or computer science, and the project involvement will be tailored to the specific interests and expertise of the student.

Mentor Biography: Leiron Ferrarese has been a postdoctoral fellow in Hiroki Asari’s group at the European Molecular Biology Laboratory (EMBL) in Rome, Italy since 2018. He received a bachelor’s degree in biology at the University of Rome “Roma Tre”, Italy, in 2006, and conducted graduate studies in neurobiology at the University of Rome La Sapienza, Italy. He then won a Ph.D. fellowship at the Max Delbruck Center where he studied dendritic integration in vivo with James Poulet, and received his Ph.D. from the Freie University of Berlin, Germany, in 2017.

As a postdoctoral researcher, Ferrarese has been studying the integration of contextual information in the early visual system of autism model mice. This project was supported first by an EMBL Interdisciplinary Postdoctoral Fellowship and currently by a pilot award from the Simons Foundation Autism Research Initiative (SFARI).

Ferrarese’s scientific interests are in studying neuronal network dynamics in mouse models of psychiatric disorders to better understand how dysfunctional behaviors may arise from anomalous neuronal computations. To this aim, he takes interdisciplinary approaches combining in vivo calcium imaging of awake mice performing a visual learning task, genetic tools for neural activity manipulation, and computational modelling of network dynamics.

Eligibility: N/A

Mentor Name: Navroop Dhaliwal
Mentor Role: Post-Doctorate
Principal Investigator: Yun Li
Institution: The Hospital for Sick Children (SickKids)
Location: Toronto, Ontario, Canada
Lab Website: https://lab.research.sickkids.ca/li/

Project Description: Investigating the mechanism of PTEN mutation-related autism in human pluripotent stem cells-derived 2D and 3D neural cultures

Mutations in the PTEN (Phosphatase and tensin homolog) gene are strongly associated with autism, macrocephaly and epilepsy. Currently, treatment options for these patients are extremely limited. In our lab, we use human pluripotent stem cells (hPSCS) based 2D and 3D culture systems to model and study the mechanism of PTEN-related neurodevelopmental disorders. We have generated PTEN mutant neurons and brain organoids that display cellular and structural over-growth, as well as increased electric activity. We are further investigating the molecular mechanism that may contribute to these PTEN mutant phenotypes. In particular, we are exploring whether mTORC1 or mTORC2 pathway activation is responsible for the PTEN phenotype. By understanding the underlying mechanisms, we aim to identify novel therapeutic targets for autism.

Mentor Biography: Navroop Dhaliwal is a research fellow in Yun Li’s lab at The Hospital for Sick Children (SickKids) in Toronto. She has a doctorate in cell and systems biology from the University of Toronto. Her Ph.D. research investigated the molecular mechanism underlying mammalian naïve pluripotency. Her postdoctoral research focuses on modeling and investigating the mechanism of PTEN related neurodevelopmental disorders in hPSCs derived 2D and 3D neural cultures. She uses CRISPR based methodologies to engineer hPSCs and differentiate them into neurons to study the underlying mechanisms. Her research aims to find potential novel therapeutic targets for autism.

Eligibility: N/A