Our research group focuses on delineating the molecular and mechanistic basis of neurotransmitter release in nerve terminals and understanding how it is altered in neurological disorders. Controlled release of neurotransmitters stored in synaptic vesicles (SV) is central to all information processing in the brain. This process relies on efficient coupling of SV fusion to the triggering signal - action potential evoked pre-synaptic calcium (Ca2+) influx. During the last three decades, the key proteins that mediate SV exocytosis have been identified. However, the precise molecular mechanisms of calcium-activation of SV exocytosis remain in the center of debate. Furthermore, mutations in these pre-synaptic proteins that affect neurotransmitter release and SV cycling are linked to a growing number of neurological disorders termed "pre-synaptic synaptopathies." For example, these include paroxysmal (epilepsy, migraine, ataxias, dyskinesia), neurodevelopmental, and psychiatric disorders. It remains unclear, though, how these mutations cause diseases. We employ multidisciplinary synaptic biochemistry, cell biology, fluorescence imaging, and structural biology tools to develop a quantitative understanding of the molecular mechanisms underlying the timing and the use-dependent plasticity on neurotransmitter release, which is essential for understanding how the brain functions in both health and disease.
Research and Training Opportunities
The Krishnakumar Lab is eager to recruit motivated postdocs and students with a particular background in biochemistry, cell biology, and fluorescence imaging. For details about open positions and opportunities, please email Dr. Krishnakumar.