Research & Publications
Understanding how complex information is reliably transmitted with millisecond precision and high fidelity from one nerve cell to another and how alterations in information processing lead to neurological disorders
Specialized Terms: Synaptic Transmission, Synaptic Regulation, Membrane Fusion, Neurological Disorders
Extensive Research Description
The release of neurotransmitters at the neuronal synapses is tightly controlled by changes in the presynaptic calcium concentration. To achieve this, synaptic vesicles (loaded with neurotransmitters) are already docked in the presynaptic membrane, ready to release the neurotransmitters when the signal (calcium ion) arrives. The protein machinery involved in this process are SNARE proteins, which catalyze the fusion of the vesicles; calcium sensors that synchronize the release of the neurotransmitter to the triggering calcium signal (Synaptotagmin isoforms) and regulatory proteins (Munc18/Munc13/Complexin ) that are involved in the organization of the release site. Our research is focused on elucidating how vesicular release protein machinery decodes the calcium signals and translate them into complex patterns of neurotransmitter release required for brain function.
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 biochemical, biophysical, and structural methods (with a specific focus on systematic biochemical reconstitution strategies) along with electrophysiology and high-resolution imaging in cultured neurons (in collaboration with Prof. Kirill Volynski, UCL Queen Square Institue of Neurology)
Synaptic Transmission; Neurology; Neurosciences