The Engines of Life

Namaste. Welcome to our webpage at the Department of Biosciences and BioEngineering, Indian Institute of Technology Bombay (BSBE-IITB). 

What is Life without motion? This motion can be visible — like a bird in flight — or, not so obviously visible like the incessant motion deep within the tiny cells in the wings of the bird. We do research on the  molecules that power all of this motion. You can call them the “Engines of Life”. Our research spans the disciplines of Biology, Physics, Chemistry and Computation. As Physicists and Engineers, can we learn from nature how to design robust machines at the Nanoscale? As Biologists, can we relate the wiggling of a molecular machine to bacterial infections, neuronal disease, obesity & diabetes, left-right asymmetry inside the body? As Computer scientists and Mathematicians, can we predict how the collective efforts of these machines create order from disorder? 

This is Nanotechnology by Nature. As real as flesh and blood, working away quietly within trillions of cells inside you, doing almost everything that you think you did.


MOTIVATION…

Ideas and tools from the physical sciences, when applied to biological problems, have yielded some of the deepest insights into the molecular dances that sustain life. Quantitative answers have been obtained through novel techniques, such as those invented to measure function of a single biological molecule. Such “single molecule” experiments are typically done with the molecule placed in an artificial (in vitro) environment. While these experiments are pioneering in their own right, it is often not possible to relate their results to real-world biology. This is because inside a cell, there is almost never anything like a single molecule. Biological molecules usually work as part of a larger complex, where many of them come together to achieve a common function. It is the NET function of this complex that is relevant, and not just that of the single constituent proteins. Our goal is to take a middle path where we extend the precision of single-molecule techniques inside living cells, or in reconstitution assays and directly measure function of a protein-complex in real-time in a cellular environment.


FOCUS …

The living cell is an assembly of specialized factories with a constant give-and-take of material occurring within them. Nanoscale proteins called Molecular motors  carry cellular material as “cargo” from one factory to the other (e.g. mRNA, vesicles, endosomes). This transport of material is essential for the cell and its factories to function. Incessant movement of cargoes of different sizes and shapes can be observed under the microscope inside living cells. The motors attach to specific cargo, and walk in a step-like manner on pre-laid tracks. In order to walk, motors generate forces about a million-million times smaller than what we use in our day-to-day life. These machines are the unit generators of force for most cellular processes. As with everything in biology, complexity throws up a challenge — different motors with inclination to walk in different directions are usually present together on a given cargo, along with a host of other non-motor proteins. How do these antagonistic motors work (or not work) together? A visually beautiful, evolutionarily important and commonly seen example of this competition between motors can be seen when fish and chameleons change colour.

The obvious, yet most remarkable thing about molecular motors is that they actually move !! We record and analyze this motion, measure the forces needed to drive this motion using optical tweezers, try to identify the molecules driving such motion using protein biochemistry, and also interfere with the motion using genetic/biochemical techniques. We use the microtubule-motor dependent motion of endosomes, phagosomes and lipid droplets as our model systems, and interrogate these systems at multiple levels of complexity.

And, then, there are the lipids on the membrane of the cargo which provide a platform for the motors to assemble before they can generate force (read more). Lipid-motor interactions are therefore likely to be a central determinant in many mechano-biological processes. Very little, however, is known about this aspect of mechanobiology. Our goal is to understand this alliance between force-generating motors and lipids. In this context, we are working on problems of direct relevance to human health. Visit the RESEARCH webpage for more details.