CSIR-Institute of Microbial Technology (IMTECH)
Sector 39-A, Chandigarh, 160036 India
Tel: +91-172-6665295 (Office), 6665296 (Lab)
Write-up of research and development interests/focus, past and present goals:
- Molecular mechanisms controlling endocytic trafficking;
- Small GTPases and their role in membrane trafficking; and
- Immunology and cell biology of pathogen/host cell interactions
Membrane trafficking is central to normal cell function, as it is essential for the internalization and transport of nutrients, segments of plasma membrane and cell surface receptors. It has been increasingly recognized that dysregulation of the membrane trafficking pathways is the underlying cause for diseases as diverse as atherosclerosis, diabetes, and cancer. Members of the Ras superfamily of small guanosine triphosphatases (GTPases) (examples: Rabs (Ras related in brain), Arfs (ADP-ribosylation factors), and Arls (Arf-like)) function as molecular switches (GDP or GTP bound) and regulate membrane trafficking by binding to a diverse array of effector molecules. In the active state, the small GTPase can bind and recruit a specific set of effectors to their site of action and can directly stimulate their activity or promote their assembly into protein complexes.
The primary research interest of our laboratory is focused on understanding the function of Arl family of GTPases that remain relatively understudied and poorly understood. In comparison to the Rab and Arf families of trafficking GTPases, the Arl GTPases form what is currently thought to be a heterogeneous group. There are over 20 Arl GTPases known and unlike Rabs and Arfs, the few Arls characterized till date are implicated in regulating diverse cellular processes such as endocytic trafficking, cytoskeletal organization, ciliogenesis etc.
We and others have recently characterized the function of one such Arl protein, Arl8 that localizes to lysosomes. Arl8 have been shown to regulate motility of lysosomes towards the cell periphery by recruiting the plus-end motor kinesin on lysosomal membranes. Recent findings from my laboratory have found that Arl8 is also present on lysosome-related organelles (LROs) such as lytic granules of Natural Killer cells. More importantly, Arl8 regulates cytotoxic function of NK cells by regulating anterograde motility of lytic granules towards the immune synapse. Current studies in my laboratory are exploring the role of Arl8 in regulating phago-lysosome fusion using Salmonella enterica serovar typhimurium as a model system. We are also exploring the function of several novel effectors of Arl8 in regulating lysosomal function.
Several members of the Rab and Arf subfamily have been shown to be aberrantly over expressed in various cancer tissues, and promote tumor aggressiveness. Very recently, ARL11 (ADP-ribosylation factor-like 11), also known as ARLTS1 (ADP-ribosylation factor-like tumor suppressor protein 1) gene deletion was found to be associated with an increased susceptibility to lung cancer, breast cancer, prostate cancer, ovarian cancer, melanoma and colorectal cancer. We are currently characterizing the subcellular localization and function of this small GTPase, and understanding the mechanisms by which Arl11 gene deletion leads to tumor progression.
To address these questions we utilize state-of-the-art techniques including confocal, super-resolution and electron microscopy, flow cytometry and protein-protein interaction techniques including immunoprecipitations, GST-fusion protein pull-down assays coupled with mass spectrometry, yeast two-hybrid analysis, antibody generation, purification and testing, molecular biology tools etc.
The lab is always open to highly motivated and hard working students.
Significant recognition: Awards, fellowships, international funding of distinction, technologies transferred/licensed etc.:
Recipient of the “Wellcome
Trust/DBT-India Alliance Intermediate Fellowship” (2015).
Received the “Innovative Young
Biotechnologist Award (IYBA)” for the year 2012 from the Department of
Biotechnology (DBT), Government of India.
Awarded prestigious Ramanujan
Fellowship (2012-2017) by the Department of Science & Technology
(DST), Government of India.
Recipient of Pre-doctoral Travel
Award (2009) from the American Society of Cell Biology.
Recipient of the Norman and Bernice
Harris Graduate Student Cancer Research Fellowship (2009).
Recipient of University of Nebraska
Medical Center Graduate Research Fellowship (2005-2008).
Present group members: