Synapses are complex molecular machines that transfer information from one cell to another via the highly regulated release of neurotransmitter from presynaptic axon terminals. Following release, neurotransmitter activates receptors on the membrane of the associated postsynaptic cell, completing the process of communication. The multifaceted nature of the synapse and its ability to change over time requires numerous developmental and modulatory mechanisms to control its formation and function. To investigate questions of synapse development, we utilize molecular, genetic, biochemical, and imaging tools available in Drosophila to study the larval neuromuscular junction (NMJ) as a model synapse. We have previously identified the protein Rab3 as playing a novel role in the formation and distribution of the presynaptic release machine among the hundreds of potential vesicle release sites that comprise an NMJ. In the rab3 mutant, visualization of essential protein components of the release apparatus reveals that release machinery is concentrated at a small fraction of available release sites. This results in the formation of a small number of “super sites” where vesicle release is enhanced while leaving the majority of sites devoid of proteins required for efficient vesicle release. The mechanism by which Rab3 performs this function is not understood. Thus, current work in my laboratory revolves around an exploration of how Rab3 functions at the Drosophila NMJ.

Witten J*, Ruschak A, Poterba T*, Jaramillo A*, Miranker AD, Jaswal SS. Mapping protein conformational landscapes under strongly native conditions with hydrogen exchange mass spectrometry. Journal of Physical Chemistry B DOI: 10.1021/acs.jpcb.5b04528 Publication Date (Web): July 6, 201510.1021/acs.jpcb.5b04528 (2015) Cohen P*, Dill K, Jaswal SS. Modeling the solvation of nonpolar amino acids in guanidinium chloride solutions. Journal of Physical Chemistry B 118, 10618–10623 (2014) Wagaman A, Coburn A, Brand-Thomas I*, Dash B*, Jaswal SS. A comprehensive database of verified experimental data on protein folding kinetics. Protein Science 23, 1808–1812 (2014) Wagaman A, Jaswal SS. Capturing protein folding-relevant topology via absolute contact order variants. Journal of Theoretical and Computational Chemistry 13, 14005-14031 (2014) Shamsuddin R*, Doktorova M*, Jaswal SS, Lee-St.John A and McMenimen K. Computational Prediction of Hinge Axes in Proteins, BMC Bioinformatics 15:S2. (2013) Jaswal SS, O’Hara PB, Williamson P, Springer A. Teaching structure: Student use of software tools for understanding macromolecular structure in an undergraduate biochemistry course. Biochemistry and Molecular Biology Education, 41, 351–359 (2013) Jaswal SS. Biological Insights from Hydrogen Exchange Mass Spectrometry. Biochim Biophys Acta Proteins and Proteomics, 1834, 1188-1201 (2013) published online October 29, 2012 Jaswal SS. Alpha-lytic protease. Handbook of Proteolytic Enzymes, 3rd edition. Elsevier Press, edited by Neil D. Rawlings and Guy Salvesen 2358–2365 (2012) Jaswal SS, Miranker AD. Scope and Utility of Hydrogen Exchange as a Tool for Mapping Landscapes. Protein Science, 16, 2378-90 (2007) Jaswal SS, Truhlar SE, Dill KA, Agard DA. Comprehensive analysis of protein folding activation thermodynamics reveals a universal behavior violated by kinetically stable proteases. Journal of Molecular Biology 347, 355-66 (2005) Jaswal SS, Sohl JL, Davis JD, Agard DA. Energetic landscape of alpha-lytic protease optimizes longevity through kinetic stability. Nature 415, 343-436 (2002) Cunningham EL, Jaswal SS, Sohl JL, Agard DA. Kinetic stability as a mechanism for protease longevity. Proceedings of the National Academy of Sciences 96, 11008-11014 (1999) Sohl JL#, Jaswal SS#, Agard DA. Unfolded conformations of a-lytic protease are more stable than its native state. Nature 395, 817-819 (1998) Mink S, Jaswal SS, Burk O, Klempnauer K. The v-Myb oncoprotein activates C/EBP beta expression by stimulating an autoregulatory loop at the C//EBP beta promoter. Biochim Biophys Acta Gene Structure and Expression 1447, 175-184 (1999) McVay LD, Jaswal SS, Kennedy C, Hayday A, Carding SR. The generation of human gammadelta T cell repertoires during fetal development. Journal of Immunology 160, 5851-60 (1998)