Elizabeth Haynes, Ph.D.

Elizabeth Haynes is a postdoctoral fellow in the groups of Kevin Eliceiri at the Morgridge Institute for Research in Madison, Wisconsin, and Tyler Ulland at the University of Wisconsin-Madison (UW-Madison). She received a Morgridge postdoctoral fellowship to develop methods for longitudinal imaging of adult zebrafish to study the cell biology of microglia across aging and disease.

Her interest in cell biology was sparked in the Bear Lab at the University of North Carolina at Chapel Hill, where she completed her graduate work on how the turnover of branched actin is crucial for directed cell migration. To better understand how cells accomplish complex behaviors and follow cues in a 3D environment, she turned to zebrafish for her postdoctoral work. As an NIH Fellowher work in the lab of Mary Halloran at UW-Madison focused on the individual roles of the cargo-binding subunits of the motor protein kinesin-1 and their function in shaping neurodevelopment and behavior. During this fellowship and as she transitions to running her own independent group, she will work to understand how microglial cell biology changes and adapts in the environment of the aging brain. Haynes will establish a 3D atlas of the aging zebrafish brain to understand regional differences in aging and pair this work with intravital multi-scale imaging approaches to understand the mechanisms underlying aging-associated changes in microglial biology.

Project: Characterizing aging microglia and their ecosystem using multiscale imaging

Microglia, the innate immune cells of the brain, have been extensively studied for their role in brain homeostasis and age-related neurodegenerative diseases. There is mounting evidence to suggest that aging-associated chronic inflammation mediated in part by microglia also drives susceptibility to neurological disease. In the aged brain, microglia can convert to a dystrophic state that hampers their ability to play a protective role and maintain brain homeostasis. Altered behaviors in aged microglia include reduced ability to detect and migrate to chemical cues and altered phagocytic behavior. The cell biology of these changes and how they arise has not been fully characterized. Zebrafish offer a genetically tractable and easy-to-image vertebrate model that can provide whole-brain context and dynamic views of aging microglia. Using a combination of cleared tissue imaging and intravital two-photon imaging in adult zebrafish, my lab will examine how the environment of the aging brain influences microglial cell biology, and how aged microglia influence brain health and cognitive function in turn. We will 1) characterize aging-susceptible and aging-resilient niches in the zebrafish brain; 2) determine the genetic pathways that drive differential aging in these areas; and 3) couple observation of microglia phenotypes with behavioral assays to understand how microglial states affect cognitive aging. Insights gained from longitudinal imaging studies in adult zebrafish will help us understand why microglia become dystrophic during aging and identify potential pathways of neural resilience.