Simons Society of Fellows Retreat 2022

Friday, March 18

Saturday, March 19

Sunday, March 20

Begüm Aydin
The Rockefeller University

The role of gut microbiota and immune activity on enteric nervous system development and maintenance

The nervous and immune systems are the main interfaces of the body that can sense and respond to environmental challenges. Interactions between the nervous and immune systems occur under steady-state and inflammatory conditions; however, the mechanisms are not understood. The gastrointestinal (GI) tract is the largest barrier surface where the body is exposed to the environment. This immense surface hosts large amounts of microbes, activated immune cells and the enteric nervous system (ENS), a vast array of neurons with remarkable diversity that control various GI functions. The dynamic interplay between the ENS, gut immune cells and microbiota creates a unique milieu with chronic, yet physiological inflammation. Thus, the ENS of the gut is an ideal system to study neuroimmune interactions upon environmental perturbations due to its proximity to immune cells and chronic exposure to environmental stimuli from the diet, microbiota and pathogens. My research will investigate the role of gut microbiota and immune activity on ENS development and maintenance.

Shortly after birth, a postnatal wave of neurogenesis occurs in the ENS that coincides with microbiota colonization and development of a mature immune system. The mechanisms by which gut microbiota and immune cells affect postnatal enteric nervous system development and maintenance are poorly understood. Our lab described that the perturbation of gut microbes by antibiotics treatment or enteric infection results in the loss of enteric neurons. Interestingly, the reconstitution of “healthy” microbiota induces neuronal recovery in adult mice. However, the mechanisms or signals causing neuronal recovery are not known. Using germ-free and gnotobiotic (mouse models with known bacterial communities) mouse models, I will investigate the effects of microbiota colonization on postnatal ENS development and identify bacterial species that induce neuronal differentiation. In combination with genetic fate-mapping tools, I will identify the origin and mechanisms of neuronal recovery upon post-inflammation microbiota reconstitutions. By doing so, my studies will reveal how microbial perturbations affect neurodevelopment and provide insights into inflammatory autoimmune and neurodegenerative diseases.

 
Philipp Brand
The Rockefeller University

Behavioral evolution in a complex world: Of food, friends and love

From dancing birds to singing flies, animals have evolved an astounding diversity of behaviors to attract and choose mating partners in their natural habitats. Guided by innate preferences and aversions, the brain filters complex environments for cues and signals to successfully navigate these reproductive behaviors in appropriate spatial, temporal and social contexts. How does the environment shape sensory evolution and contribute to the diversification of mating behaviors? Using the highly tractable insect nervous system as an inroad, I study the neural mechanisms underlying the evolutionary ecology of reproductive behaviors and how the environment contributes to their diversification.

In Drosophila fruit flies, courtship and mating occurs on fermenting food where many individuals congregate. Replicating this naturalistic context in the lab, I discovered striking differences in the sensory dependence of mating behaviors across species. Most notably, Drosophila erecta requires the presence of food to engage in courtship and only mates in social groups. Using a combination of experimental ethology, in vivo functional imaging, genetic manipulation and optogenetics across species, I revealed that sexual arousal in D. erecta is uniquely gated by food odors that switch the valence of visual stimuli leading to courtship and mating. This provides a possible neural mechanism underlying the environmental modulation of reproductive behaviors, highlighting how social behaviors are shaped by the natural environments in which they evolve.

 
Moses Chao
New York University

Longevity of neuronal populations

Little is known about how neurons become dependent and independent of trophic support. The basis of a switch in dependency for trophic factors is not known. This question is relevant since the inability of mature neurons to maintain or lose resistance to trophic factor deprivation may underlie the development of neurodegenerative diseases.

 
Raphael Cohn
Columbia University

The Marvelous Moving Maggot

Controlling body movement is among the most essential jobs of animal nervous systems. Maintaining precision and speed of movement despite changes in environment, body size and injury necessitates the use of sensory feedback to adaptively modify motor circuits. Proprioceptive neurons, internal sensors of body position and strain, are particularly well-suited for this task. These neurons must coordinate their growth and positioning with the musculature and epidermis in which they are embedded, presumably through a molecular signal released by these other tissues. However, the body is innervated by many different types of sensory neurons, and their specialized functions likely require distinct responses to such signals.

The body wall of the Drosophila larva contains several types of proprioceptors, as well as neurons that sense touch and pain. This system has proven to be an excellent model for understanding how these different neuron types attain their identities, including distinct dendritic arbors that are specialized for their individual sensory functions. We have identified a signaling pathway that is most strongly active in the proprioceptive neurons and dissected how expression of this pathway is differentially controlled during the development of each type of neuron. Interestingly, this pathway is downstream of Nitric Oxide, a molecule that is known to be released in response to stretch in many tissues. This suggests the intriguing possibility that this pathway may be responsible for coordinating the response of different tissues and neuron types to environmental and developmental perturbations in order to maintain the precise feedback necessary for adaptive motor control.

 
Aleksander Doan
Columbia University

Gauge fields and geometry

In the 19th century, Maxwell explained electricity, magnetism, and light as effects of the electromagnetic field, whose dynamics is governed by the equations named after him. While Maxwell’s principal goal was to explain natural phenomena, he pointed out that his theory had interesting connections to some purely mathematical problems studied by geometers. For many years, this observation remained merely a curiosity. Today, we understand it as part of a much deeper story, relating geometry to gauge fields: generalizations of the electromagnetic field. The goal of the talk is to explain this story, with a focus on new developments involving Calabi-Yau manifolds, a mysterious class of higher-dimensional geometric shapes which for the last forty years have fascinated mathematicians and physicists alike.

 
Michele Fornea
Columbia University

On remarkable solutions to elliptic curves’ equations

I will explain how analytic methods (~calculus) conjecturally produce remarkable algebraic solutions (~fractional numbers) to elliptic curves’ equations: y^2=x^3+Ax+B.

 
Jiaoyang Huang
New York University

Random Matrix Statistics

The success of random matrices in modeling physical systems lies in the universality phenomenon of their eigenvalue statistics. The general belief is for systems with a lot of independence, such as a population’s weight distribution, we expect to see the bell curve. However, for systems with many strongly interacting components, we expect to see random matrix statistics. In this talk, I will first discuss some background concerning random matrix statistics. Beyond matrix setting, random matrix statistics are conjectured to govern the asymptotic behavior of various random growth models and interacting particle systems. Next, I will show you some beautiful pictures of various models and discuss recent results proving random matrix statistics for these models.

 
Emily Mackevicius
Columbia University

Probing how the hippocampus forms one-shot memories using memory expert birds

The hippocampus is critical for forming instantaneous (one-shot) memories. What happens in the hippocampus at moments of memory storage and recall? We have developed a strategy to address this question — recording the hippocampus of memory expert birds from the food-caching chickadee family. These birds prolifically hide food items in scattered locations, then return later to retrieve food using memory. We have recorded, using calcium imaging, large populations of neurons from the hippocampus during bouts of food caching and retrieving. I will present evidence for transient memory-related activity in the hippocampus and reactivation of cache-related activity patterns preceding moments of food retrieval. I will compare this transient memory-related activity to sustained changes in hippocampal activity that have been described to occur near locations where an animal consistently receives reward. Finally, I will relate these two modes of hippocampal activity in the context of a predictive model of hippocampus function.

 
Carol Mason
Columbia University

Seeing binocularly: Why albinos lack stereo vision

In higher vertebrates, including humans, retinal ganglion cells (RGCs) extend their axons to the same (ipsilateral) or opposite (contralateral) side of the brain to ensure stereo vision. In albinism, a genetic condition in which pigment (melanin) is disrupted in the skin and eye, the ipsilateral eye-to-brain projection is diminished, altering the architecture of the binocular circuit. Albinism therefore is a good model for investigating the cellular and molecular mechanisms that confer RGC properties during the establishment of the binocular circuit. In the albino retina, compromised competence to generate ipsilateral projecting RGCs is due to the downregulation of cyclin D2, a protein that controls the tempo of the cell cycle. Consequently, albino mice that were also cyclin D2-deficient pigmented exhibit a diminished ipsilateral eye-to-brain projection and compromised depth perception. In albino mice, pharmacological stimulation of calcium channels, known to upregulate cyclin D2 in other cell types, normalizes cyclin D2 expression and the ipsilateral RGC population and improves depth perception. These findings highlight cell cycle regulation by cyclin D2 as critical for the formation and function of the mammalian binocular circuit. They also provide an inroad to understanding how melanin disruption in the retinal pigment epithelium in albinism affects the production of RGCs, a long-standing puzzle.

I will also talk about careers: Tools and guidelines are currently plentiful for navigating your next steps in academia and beyond — how to communicate your science and present yourself, how to apply and interview for faculty or industry positions, on mentoring “up” and “down,” but little on what you do when you get to that next step. Although the Senior Fellows have been informally advising Junior Fellows on these topics in the last years, we will discuss how to formalize this training during the retreat and at our gatherings in New York.

 
John Morgan
Columbia University

High Dimensional Topology and Geometry

A central theme of mathematics is generalization. Higher dimensional spaces are a generalization of two- and three-dimensional spaces accessible to us by direct visualization. Even though we cannot directly visualize higher dimensional spaces, we can define them precisely, and we can study their (very rich) mathematical structure.

In this talk, I will give some elementary examples of higher dimensional spaces and talk about how mathematicians think about them and gain an understanding of their properties. I will also discuss the relation of and differences between topology (the study of form) and geometry (the study of measurement).

 
Tony Movshon
New York University

Why Monkey Research Matters to Brain Science

Neuroscience is based on the experience of physicians treating brain disorders and on the work of scientists studying the brains of animals. The work of physicians helps us to understand the structure of the brain and the mind, but it is work with animals that makes it possible to achieve a mechanistic understanding. Many laymen, and many scientists, view research with animals with distaste or dismay. That goes particularly for research with monkeys, our close evolutionary cousins, which are often the best models for human brain function. Monkey research is under threat in many parts of the world, putting both advances in human knowledge and advances in medical science at risk. Tony Movshon will discuss the benefits of monkey research, the nature and extent of the forces that threaten it, and how thoughtful consideration of the ethical foundations of animal research can help us find our way through.

 
Amy Norovich
Columbia University

Probing the neural basis of visually-evoked aggression in Siamese fighting fish

Aggression is a universal behavior that shapes human and animal societies. In humans and other primates, visual information plays a prominent role in eliciting aggression, yet in rodent and fly models commonly used in behavioral neuroscience, aggression is evoked largely by smell and pheromonal cues. Thus, how visual cues influence aggressive behavior — and social behavior more generally — remains relatively unexplored.

Siamese fighting fish (Betta splendens) have been bred for hundreds of generations to select for extreme aggression that is evoked solely by visual cues and is markedly more prominent in males than females. Thus, Betta is an ideal model for studying the neurobiology of visually evoked aggression and how the same socially salient visual cue drives sex differences in behavior. I have developed behavioral assays that reliably elicit aggression in adult Betta, as well as machine learning-based methods to analyze the behavior. I have used molecular methods to identify several brain regions associated with aggression and to determine how these regions intersect with the visual system. Going forward, I am characterizing gene expression in these regions to identify molecular pathways mediating sex differences in behavior and developing physiological methods to examine neural activity in real time.

 
Fedor Popov
New York University

Can Quantum Field Theory End in a Big Mess?

We study various quantum field theory with O(N1)×O(N2) symmetry. In studying the behavior of the model in the space of N1 and N2, we find points where zero-Hopf bifurcations occur. In the vicinity of these points, we provide analytical and numerical evidence for the existence of Shilnikov homoclinic orbits. The latter is particular interesting since it induces chaotic behavior in the RG flow. As a simple warm-up example for the study of chaotic RG flows, we also review the non-hermitian Ising chain and show how, for special complex values of the coupling constant, its RG transformations are chaotic and equivalent to the Bernoulli map.

 
Joan Pulupa
Columbia University

Visualizing gene regulation in olfactory sensory neurons using live-cell fluorescence microscopy

The three-dimensional organization of genetic information in higher organisms is critical for proper gene regulation. Although significant progress has been made in identifying the organizational principles of the genome, little is known about the dynamics of nuclear architecture and how these dynamics interact with gene expression. As biologists, many of the tools that we use provide static information. To study the inherently dynamic process of gene expression, I am employing new live-cell imaging technologies to generate unprecedented temporal resolution.

I have chosen to investigate the most striking example of genome organization leading to gene regulation: olfactory receptor (OR) choice by olfactory sensory neurons (OSNs). In mature OSNs, only one OR gene out of >1000 potential OR genes is expressed, and the process by which the expressed OR is activated is stochastic. OR gene activation is accomplished by the formation of a hub that brings together loci from various chromosomes and associates with and activates a single OR gene. This hub forms under the control of various regulatory proteins including the transcription factors, Lhx2 and Ebf, and the adaptor protein Ldb1. In OSNs, I have fluorescently labeled the genomic loci of the expressed OR and these regulatory proteins, allowing me to monitor their dynamics in living cells. By studying these dynamics, I will gain insight into the interplay between changing genome architecture and gene regulation.

 
Pooja Vishwanathan
Mount Sinai

Generalization and abstraction in the brain

Brains are expert general learners, generalizing learning across new stimuli and tasks. This is something deep neural networks struggle to do. In primates, the prefrontal cortex has greatly expanded through evolution. Neural populations in the primate prefrontal cortex exhibit a great range of dynamics to support general learning. We approach our study of what makes brains such experts at generalization by designing behavioral tasks with different demands. My talk will introduce some such tasks and the dynamics we observe in the primate prefrontal cortex neurons during ongoing behavior. I will discuss how these neuronal populations generalize to new information to support decision making and how they can enable abstraction and new learning.

 
Songtian Sonia Zhang
Columbia University

Spatial study of quantum materials with nanolight

Quantum materials is a rightfully broad term to encompass once disparate fields of physics, centered around ’emergent phenomena.’ While emergent phenomena can be found throughout nature, for example in the oft invoked schools of fish and flights of swallows, the complexity greatly increases when these interactions emerge on atomic and quantum length scales on the order of nanometers. The most direct scientific investigation methods have always been visual — but what happens when the science occurs at a resolution beyond the limits of light itself? This talk will introduce a recent technique known as SNOM (scanning near-field optical microscopy) that allows us to study these emergent phenomena with the requisite nanometer resolution. This has allowed a resurgence of interest in decades-old systems such as superconductors and 2D (two-dimensional) materials, as once inaccessible physics emerge under these new measurement techniques. This talk will explore the role of 2D materials in the continued exploration of even the smallest aspects of quantum materials and the place SNOM occupies in this ever growing scientific endeavor to push our understanding beyond the limits.