Roop Mallik's research can have an impact on diabetes as well as Alzheimer's

Biophysicist and Infosys Prize winner Roop Mallik has been studying the transport of small particles inside living cells, and his research could impact everything from diabetes to Alzheimer’s.

When city-based Roop Mallik received the Infosys Prize for his work in the area of life sciences in Bangalore on January 5, it was the second time that the country’s foremost academics had recognised the significance of his research. Back in 2014, Mallik, now 48, was awarded the prestigious Shanti Swarup Bhatnagar Award for his contribution towards understanding the functioning of molecular motors. These are essentially motor proteins within the cells of the human body that transport substances to specific regions, thereby allowing the body to achieve various biological functions.

It’s a complicated subject, of course, but Mallik, a professor in the department of biological sciences at Tata Institute of Fundamental Research (TIFR), summarises it with an analogy so simple, it could be the plot of a children’s picture book: “The motion inside the cells in every part of the body is generated by motor proteins. Think of these as porters on a platform at a railway station. They are carrying these suitcases — which may be bacteria, balls of fat, pathogens, mitochondria and such — and their job is to move these suitcases from one spot to another. The broad questions that we have been asking are: how do they recognise what to carry, and when they do, how do they get from one point to the other?”

The motion Mallik is referring to occurs at the speed of just a few microns per second, but when it doesn’t, the result is disease. “Neurological disorders, for example, result from the improper transport of material (like mitochondria) inside the cells of your brain,” Mallik says, as he walks briskly down a corridor of the TIFR facility in Colaba.

“We are looking at how motor proteins carry bacteria/pathogens to be degraded inside the immune cells of the body — essentially, how pathogens get killed, and when they do not, why not,” says Mallik, who has focused on this field for almost 16 years. He has also been measuring the force that these motors exert to transport the particles. “We can shine a laser light into the cells, see the porter carrying the suitcase, and then shine a light on the suitcase. The laser light exerts a small force on this suitcase — bacteria, for instance — and it tries to hold this object in one place,” he says, returning to his analogy. “This process is called ‘optical trapping’, and it is possible to measure the force, thanks to a device that’s similar to the optical tweezers invented by American scientist and Nobel prize winner Arthur Ashkin. If the motor protein wins the tug of war against our trap, the motor must be stronger than it, and the force our trap exerts can be calibrated.”

Complemented by their research in genetics and microbiology, these measurements allow Mallik and his team to monitor the activity of motor proteins in real time.

The other aspect of his work has to do with obesity and diabetes.

“Like pathogens, fat particles — lipid droplets, which are tiny balls of fat — are also transported by motor proteins,” says Mallik. He explains that in the fed state, the liver receives a little fat, which it chews up efficiently, and sends into the blood stream as lipoprotein. “However, in the fasted state, the liver gets ten times as much fat, as the brain signals the adipose tissues to send fat its way. If the liver was to send all this fat into the blood, it would be taken up by the heart and brain very quickly, and a person would die. That this does not happen through our daily feeding-fasting cycles means that the liver has some means to close the tap on fat.”

Mallik’s team found that while, in the fed state, kinesin motor proteins “jump on lipid droplets and carry them to the appropriate region where they are repackaged as lipoprotein; in the fasted state, the motors simply fall off lipid droplets.” Their discovery of this fundamental mechanism, he tells us, is important not just for obesity and diabetes management, but also for Hepatitis C.

Mallik, who was born in Allahabad, says that, as a physicist, he’s always been fascinated by things that move — that’s what drew him to this area of biology. And, the man is constantly on the move himself. He loves trekking through remote mountains.

Thomas Pucadyil, of the Indian Institutes of Science Education and Research (Pune), who received the Bhatnagar Prize last year for his work on cell biology, is excited about Professor Mallik’s contribution to the understanding of human biology. “It’s been a real challenge to understand how these proteins work in cells, and Roop’s intrinsic comfort with Physics has come in handy here,” says Pucadyil. “His work opens up the possibility to work with these motors and tinker with the processes of immune cells.”

Meanwhile, Mallik has started working on the next step. “We are developing a more visually-appealing system to see all of this under a microscope. What we were using so far, were somewhat artificial systems — cultured cells — but we will now start doing research on fish.” Then, he aims to study whether it’s possible to externally control mechanisms such as the lipid protein-to-lipoprotein conversion in the liver. “In fact, we have made some progress in that direction already,” he says. But he adds with a laugh that it’s too soon to celebrate. “Just don’t expect a new drug the day after tomorrow.”

Roop Mallik is a professor in the department of biological sciences at Tata Institute of Fundamental Research


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