Prof. Roop Mallik, from TATA Institute of Fundamental Research (TIFR), Mumbai, bagged the Infosys Prize 2018 in Life Sciences. His work on the molecular motor proteins helps us to understand how they transport pathogens and fats inside the liver cells. He is also the recipient of the prestigious Shantiswarup Bhatnagar award in 2014.
Imagine a truck or a lorry transporting the cargo from one city to another. Similarly, inside our body cells, there are several small vehicles called motor proteins which transport substances from one part of the cell to another. The cargos can be bags or tiny vesicles containing fats or proteins, or some cellular components, or even pathogens like viruses. The vehicles or motor proteins are called kinesin and dynein, and they transport cellular cargo towards opposite ends of tracks or highways called microtubules. Thousands of these cargos are transported on busy cellular highways at any given time.
What are the consequences if the cargo is not transported at the right place and at the right time? If the transportation mechanism gets stalled or altered, it can lead to many disease conditions. One such example is Alzheimer's disease, a neurodegenerative condition, in which the kinesin and dynein function severely impedes causing the breakdown of transportation mechanism in the nerve cells in the brain.
How do these motor proteins know which vesicle or cargo they are supposed to carry and when are they supposed to carry?
At Tata Institute of Fundamental Research, Mumbai, Dr. Roop Mallik, and his lab have been precisely working on these fundamental questions using multi-disciplinary approaches from physics, computation, chemistry, and biology.
They have unveiled a fundamental mechanism that allows the liver cells to control fat secretion into blood. When we eat and feel satiated, the liver makes fats and secretes them into the blood. During this process, the cargo full of fats binds to the motor protein kinesin which transports the fat out of the liver cells into the blood. However, when we are fasting, the cargo containing fat doesn’t get secreted out in blood. In such a condition, kinesin does not bind effectively on the cargo. Even if motor-kinesin binds to the cargo, it keeps falling off, thereby decreasing the speed of transportation. This decreases the secretion of fats from the liver, which helps maintain fat balance in the blood. Prof. Roop and his team captured these events using advanced optical-laser tools.
This entire process of fat secretion by the liver is controlled by insulin. It may be possible that the inability of the liver to control fat secretion across feeding/fasting cycles may be an initial phase for diseases like fatty liver, obesity, diabetes, and cardiovascular diseases.
Prof. Mallik and his team are also investigating how motor-fat assemblies are used by dreadful viruses like Hepatitis C virus. This virus infects the liver cells and multiplies to infect other cells. By blocking such assemblies in future, it could be possible to stop the virus from infecting other cells.
Prof. Mallik's research looks promising and may help in developing specific therapies for liver-related and physiological disorders like obesity and diabetes in the future.
Edited by: Geeta Goregaonkar
- Molecular Adaptations Allow Dynein to Generate Large Collective Forces inside Cells https://doi.org/10.1016/j.cell.2012.11.044