THEME: "Frontiers in Neuroscience and Brain Disorders Research"
Yale University, New Haven, CT, United States of America
Title: Mechanistic Investigations Into the Brain Derived Neurotrophic Factor Receptor TrkB
Mary Avella is a rising senior at Hunter College pursuing a degree in psychology with a concentration in
Physiology Psychology. Last summer, Mary conducted research in Dr. Matthew Nassar’s lab at Brown
University. Her project focused on how neurotypical and autistic people learn in a stable or flexible way,
with specific relation to attention to details. This summer Mary worked in Dr. Moitrayee Bhattacharyya’s
lab, where she is looking at the mechanisms of the Brain - Derived Neurotrophic Factor receptor TrkB.
Mary works at Dr. Leora Yetnikoff’s lab in New York City, at the College of Staten Island, during the
school year. Her project is looking at looking at dopamine axons in the medial prefrontal cortex in
socially isolated adolescent female mice. Mary is interested in the genetic biomarkers that affect brain
areas that control social behaviors in autistic females. She is currently applying to PhD Neuroscience
programs.
Psychedelics have become a new therapeutic treatment for mental illnesses like depression. One
key mechanism of the neural targeting of these drugs is the neurotrophic factor BDNF binds to the
tyrosine kinase receptor B, because both BDNF and TrkB contribute to cell growth, function, and death.
A key feature of this dynamic is the change in the oligomeric distribution(interaction of subunits with
each other), in order to see changes in function and structure. The objective of our experiment was to see
what the oligomeric distribution of TrkB in response to BDNF on the membrane. We grew Expi-293 cells
and measured 24 hour and 48 hour time periods. We broke open the cells, extracted and solubilized the
membranes, performed fluorescence size exclusion chromatography and native-nanobleaching in order to
check TrkB protein quality and oligomeric distribution on the membranes. We found that there was better
expression after 48 hours, with a more complex oligomeric distribution, and more dimer-trimer formation
with BDNF. Future research should look to solve the structure of full-length TrkB with detergent and
native-nanodiscs, using Cryo-EM, with and without BDNF or psychedelics.