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RAMANUJAN FELLOWS AMIT TULI Institute of Microbial Technology Sector 39-A Chandigarh-160036, Punjab [email protected] Amit Tuli obtained his B.Tech. (Biotechnology) in 2004 from Guru Gobind Singh Indraprastha University, Delhi, India; and Ph.D. (Biochemistry and Molecular Biology) in 2009 from the Department of Biochemistry and Molecular Biology/Eppley Cancer Center, University of Nebraska Medical Center, USA. After post-doctoral fellowship in the laboratory of Dr. Michael B. Brenner at the Brigham and Women’s Hospital/Harvard Medical School, USA, Amit joined the Institute of Microbial Technology (IMTECH), Chandigarh, India as a Ramanujan Fellow in February 2012. RESEARCH DESCRIPTION Lysosomes, discovered more than 50 years ago, are dynamic acidic membrane-bound cytoplasmic organelles found in all mammalian cells. They play critical roles in the physiology of cells and organisms by serving as the major site of degradation of macromolecules delivered via secretory, endocytic, autophagic and phagocytic membranetrafficking pathways. Therefore, lysosomes are historically considered to be the endpoint of the endocytic pathway. Recent research indicates that our knowledge and perceptions about lysosomes as 'suicide bags' or 'garbage disposal units', no longer apply. Research has shown that besides acting as a degradative organelle, lysosomes can undergo regulated secretion and exocytosis. For example, during an injury to a cell, a rapid repair response is generated that patches the affected area by adding lysosome-derived membranes at the cell surface disruption site. Also, in certain specialized cells of our body (mainly of the immune system) lysosomes are pleiomorphic and contribute to forming many different classes of physiologically important secretory organelles, collectively termed as Lysosome-Related Organelles (LROs), which can be undergo regulated exocytosis in response to an external stimulus. Examples of LRO-related trafficking include: melanosomes in melanocytes, lytic granules in Natural Killer (NK) cells and Cytolytic T Lymphocytes (CTLs), and granules in mast cells, platelets, basophils and neutrophils. These new unanticipated functions make the lysosome a dynamic organelle and not simply the end point of the endocytic pathway. In humans, many diseases result from errors in the lysosomal trafficking/secretion. So far the molecular mechanism(s) controlling lysosomal motility and exocytosis are still not known. Specifically, what proteins mediate the motility of lysosomes/LROs on microtubule network; what enables lysosomes to take on the dual role of secretory organelle and degradative organelle; and to what extent are these processes similar and different between different cell types. These are the innovative questions our research work aims to understand. SELECTED PUBLICATIONS Andrews, N.W., Membrane repair and immunological danger. EMBO Rep, 2005. 6(9): p. 826-30. Stinchcombe, J.C. and G.M. Griffiths, Secretory mechanisms in cell-mediated cytotoxicity. Annu Rev Cell Dev Biol, 2007. 23: p. 495-517. Orange, J.S., Formation and function of the lytic NK-cell immunological synapse. Nat Rev Immunol, 2008. 8(9): p. 713-25. Cox, T.M. and M.B. Cachon-Gonzalez, The cellular pathology of lysosomal diseases. J Pathol, 2012. 226(2): p. 241-54. 114