Shyam Krishnakumar, PhD

Research Scientist in Cell Biology

Research Departments & Organizations

Rothman Lab

Research Interests

Cell Biology; Neurosciences; Synaptic Transmission

Research Summary

Understanding how information is transmitted reliably with sub-millisecond precision from one nerve cell to another and how alterations in information processing leads to neurological disorders

Specialized Terms: Synaptic Transmission, Synaptic Regulation, Membrane Fusion, Neurological Disorders

Extensive Research Description

Regulation of Synaptic Transmission 

The release of neurotransmitters at the neuronal synapses is precisely timed to follow the arrival of a nerve impulse. To achieve this, synaptic vesicles (loaded with neurotransmitters) are already docked in the presynaptic membrane, ready to release the neurotransmitters when the signal arrives. The protein machinery involved in this process are SNARE proteins, which catalyze the fusion of the vesicles; and set of chaperones (Munc18/Munc13) and regulatory proteins (Complexin and Synaptotagmin), which synchronize the release of the neurotransmitter to the triggering signal (calcium ions). Our research is focused on elucidating the molecular architecture at the presynaptic terminals and determine the precise sequence of molecular events that leads to Ca2+-triggered synaptic vesicle fusion.  

The controlled release of neurotransmitters is central to information processing in the nervous system, and is altered in many psychiatric and neurological disorders as is clear from well-established clinical benefits achieved by drugs that modulate neurotransmitter biochemistry and/or availability. So, we also aim to uncover the molecular and mechanistic basis for neurological disorders.

Our strategy is based on the systematic quantitative analysis of mutations both novel structure-based designer mutants as well as ‘experiments of nature’ - mutations associated with neurological disorders. We employ multidisciplinary approaches including biochemistry, biophysics, structural biology, cell biology including super-resolution microscopy, electrophysiology, live neuronal imaging, and computational modelling.

Selected Publications

See list of PubMed publications

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