The Infosys Prize 2018 in Life Sciences is awarded to Prof. Roop Mallik for his pioneering work on molecular motor proteins, which are crucial for the functioning of living cells. Mallik has identified and measured forces needed to transport large particles inside cells, and demonstrated their role in fundamental processes such as targeting pathogens to their destruction and moving lipid droplets for fatty acid regulation in the liver.
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The Little Engines That Can
Scope and Impact of Work
Prof. Roop Mallik is an internationally known cell biologist and a specialist in the field of mechanobiology, specifically, how active biological motion is generated in cells and tissues. His work has focused on the cytoskeletal motor proteins of the kinesin and dynein families that drive much of intracellular biological motion. These mechanochemical enzymes generate forces required to deform and divide cells, make cells move, transport cargoes, and generate spatiotemporal patterns inside cells.
Dysfunctional motors cause a variety of diseases ranging from developmental abnormalities to neurological disorders. To understand how a motor moves cargoes, it is important to measure the picoNewton levels of force generated by motors directly inside living cells. Prof. Mallik pioneered a new model system, namely movement of single phagosomes on microtubules inside living cells. Using cutting-edge techniques such as optical tweezers, he made the unexpected discovery that each dynein motor uses an "automatic gear" to enable it to perform efficiently in large teams.
Mallik also discovered that the geometrical organization of dynein is modified by clustering dynein motors into the cholesterol rich lipid domain of the phagosome membrane. These findings are important for understanding how cells degrade pathogens contained in phagosomes by their trafficking to lysosomes.
In another line of research, Mallik uncovered a fascinating connection of vesicular transport to insulin signaling and lipid metabolism in the liver. He showed that kinesin motors play a novel role of tethering lipid droplets inside liver cells. The liver controls lipid homeostasis and Mallik’s findings explain how triglyceride levels are controlled by lipoprotein secretion from liver cells, in normal and fasting conditions. These results provide fundamentally new insights into lipid homeostasis and will help generate better therapeutics for liver-related pathologies.
Mallik’s breakthroughs are borne from his insightful use of advanced techniques to address basic questions in biology. His fundamental discoveries in turn provide insight into diverse disease processes.
Bio
Prof. Roop Mallik is an Professor in the Department of Biological Sciences at Tata Institute of Fundamental Research, Mumbai. Prof. Mallik completed his Master’s in Physics from Allahabad University, before completing his Ph.D. in Condensed Matter Physics at TIFR, Mumbai.
Mallik was a Human Frontier Sciences Program (HFSP) Long-term Postdoctoral Fellow (2001-2006) at the University of California, Irvine. From 2001-2005, Mallik was also a Postdoctoral Fellow in Biophysics at UC, Irvine where he explored in vitro studies of Molecular motors cytoplasmic dynein and kinesin.
Prof. Mallik is a recipient of the Shanti Swarup Bhatnagar Award in Biology (2014). He was International Senior Research Fellow with the Wellcome Trust (UK) from 2006-2012. Mallik has been Senior Fellow with the Wellcome-DBT India Alliance since 2013. He is a Fellow of the Indian Academy of Sciences (Bangalore), and Member, Guha Research Conferences.
Timeline
Jury Citation
The Infosys Prize 2018 in Life Sciences is awarded to Prof. Roop Mallik for his pioneering work in the field of intracellular transport. Mechanical motion in general, and the movement of cargoes in particular, are basic functions of all living cells. Prof. Mallik has advanced the use of molecular tweezers, biochemical approaches, and genetics to identify and measure the forces needed to transport large particles inside cells.
Mallik’s groundbreaking findings have revealed how molecular motors, including dynein and kinesin, move phagosomes and lipid particles. This helps understand how pathogens contained in phagosomes are sent for their destruction in lysosomes and how triglycerides are exported by liver cells. These fundamental discoveries provide insight into mechanisms of diverse diseases.
“I congratulate you on winning the Infosys Prize in Life Sciences. The prize recognizes your pioneering work in unravelling the movement and control of traffic inside cells. Your discoveries of the mechanisms by which molecular motors move cargoes on cytoplasmic tracks are helping us understand fundamental and diverse cellular processes, such as how our bodies target pathogens for their destruction and release fats from liver cells.”
