PROJECT SUMMARY / ABSTRACT
What fascinates me is the ability of the nervous system to mediate our adaptive responses to our
changing environment and our changing behavioral states. As an entry point into this phenomenon, in my
graduate training, I’ve used the Drosophila neuromuscular junction (NMJ) to build expertise in applying
genetic and molecular analysis to understand how neural circuitry is adapted downstream of physiological
input. In this context, at the cellular level, I’ve been most curious as to how neurons and their targets adapt
highly specialized and complementary cellular morphologies during synaptic morphogenesis (SM). At the
molecular level, neural activity initiates the deployment of calcium-dependent transcriptional and post-
transcriptional programs that regulate synaptic morphology and organization. After learning about factors that
control local translation within the synaptic compartment, such as the fragile X mental retardation protein
(FMRP), I became very interested in post-transcriptional control of SM. Mechanistically, I am interested in
how the translation of individual genes is controlled downstream of neural-activity during SM, which lead me
to studying miRNAs. In my dissertation work thus far, I have identified several miRNAs as essential for activity-
dependent morphogenesis of the NMJ terminal including miR-973. MiR-973 loss of function revealed a novel
phenotype and suggested that it is required for activity-dependent synapse stability.
Through these efforts, I have developed a sound understanding of approaches to characterize changes
in synaptic architecture and plasticity. I will build upon this skill set in the F99 phase of this proposal by using
optogenetics, ribosome profiling, and genetic approaches to resolve the mechanistic contribution of miR-973
in synaptic stability at the NMJ. Concurrently, I have developed a training plan with my sponsor and co-
sponsor to ensure that I am actively thinking about the broader relevance of my work to synaptic plasticity in
mammalian systems. Collectively, training during the F99 phase will provide a solid foundation that will enable
me to construct effective experimental approaches to studying neural plasticity in a broad range of contexts.
Moving forward, I will be in great position to transition into the K00 phase where I will apply my expertise in
synaptic morphogenesis to exercise-mediated neural plasticity in the adult mammalian brain. My ultimate goal
is to utilize this approach to identify novel molecular pathways and signaling factors that mediate neural
plasticity as potential targets for therapeutic applications, which aligns with the Brain Initiative on
Neurotherapeutics and Mechanisms shaping neuronal circuitry.