Research Projects

Inter-organelle membrane contact sites (MCS) are classically defined as juxtaposed regions between two intracellular organelle membranes that interact through protein tethers. Recently, it was identified that lysosomal GTP-bound RAB7 promotes the formation of highly dynamic mitochondria-lysosomal membrane contact sites (MLMCs). These MLMCs have been found to regulate multiple cellular functions, including mitochondrial and lysosomal organelle network dynamics, mitochondrial Ca2+ transport, and cholesterol trafficking. However, the detailed molecular architecture responsible for MLMCs in mammalian cells still needs to be understood. Apart from the molecular architecture of MLMCs, bona fide markers for forming MLMCs, dynamic spatiotemporal resolution, and their comprehensive roles in neurodegenerative disorders are yet to be explored. In this context, we will be particularly interested in developing Sulfo-Rhodamine based Near-Infrared (NIR) calcium fluorescence probes with tunable binding affinities to target intracellular organelles to understand how the intracellular dynamics and calcium signaling events are regulated in mammalian cells. In addition, we will be interested in using our new NIR fluorescence Ca2+ probes as a high-throughput screening platform to identify target proteins that misregulate the Ca2+ dynamics in neurons and explore potential therapeutic interventions for the early progression of neurodegenerative disorders. Thus, with this proposal, we hope to gain further insights into organelle biology and understand “chemical conversations” between the organelles that occur at the molecular level under physiological and pathophysiological conditions.