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Mechanism of Insulin release in type 2 diabetes

Insulin granule exocytosis is tightly regulated by the SNAREs, which are highly conserved proteins that closely resemble the vesicle fusion mechanism in neurons as well as exocrine and endocrine cells. While there is information available on the associated protein machinery, the exact identity of the protein involved in biphasic release is still under debate. It has been proposed that several Syt isoforms (Syt1, 2, 3, 4, 5, 7, 9) play a role in insulin exocytosis in β-cells. Similarly, insulin secretion is mediated by multiple VAMP and Syntaxin isoforms (VAMP8, Syntaxin 3, 4) in addition to the canonical isoforms Syntaxin 1 and VAMP2 (70-72). Thus, the identity of the SNARE proteins and the associated regulatory elements are still a matter of debate. A systematic approach to identify physiologically relevant SNAREs and SYT isoforms involved in insulin secretion is essential. Our lab is working to identify the key proteins and how they are compromised in type 2 diabetes.

Molecular Pathogenesis of Neurological Disorders

The mechanisms governing synaptic transmission are critical to our understanding of how information is transmitted in the brain, yet they remain among the most fundamental unresolved questions in neurobiology. Numerous presynaptic processes are often affected in neurological diseases, including Schizophrenia and Alzheimer’s disease. Direct examination of presynaptic processes has historically been limited by the resolution constraints of conventional approaches. The long-term goal of my research program is to reconstitute synapse on a chip and apply nanoscale resolution approaches to understand the fundamental mechanisms of synaptic transmission in central synapses under normal conditions, and what disruptions lead to disease states.

Development of Suspended lipid bilayer platforms

A major focus of our group is the development and application of artificial suspended lipid bilayer platforms. These are useful as cell membrane models, allowing scientific study of individual cell membrane components such as lipids and proteins. Many applications utilizing artificial suspended lipid bilayers would benefit from improvements in the underlying lipid bilayer technology, including reconstitution of biological processes, small molecule drug discovery, cell signaling, organization and biophysics of macromolecular complexes.

 

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