Bengaluru: Alongside infections and diseases, lifestyle disorders such as diabetes and obesity abound in today’s world. Globally, 1.9 billion adults are overweight and 650 million are obese. In India, obesity is a major risk factor for cardiovascular disease and affects about 30 per cent of the population.
Understanding how fat deposits work in the human body greatly aid in tackling the problem of obesity, and one of several scientists working on this subject is Roop Mallik of the Tata Institute of Fundamental Research (TIFR), Mumbai.
Mallik works on understanding motor proteins that are responsible for moving around tiny globules of fat, as well as pathogens, to and from various parts of a cell. And his work has earned him two prestigious awards — the Shanti Swarup Bhatnagar Prize in 2014, and the the Infosys Prize for Life Sciences in 2018.
Armed with a PhD in condensed matter physics (1999), Mallik eventually transitioned to studying biological processes when he realised his interest in explaining biological phenomena using simple physics.
“There are processes happening at extremely small scales of micro and nanometres in our body,” Mallik said. “And these end up translating into various diseases and conditions on such a large scale. It is fascinating to me that biological processes could be explained using simple physical and mathematical principles, just like physics.”
Motor proteins and why they’re important
The crux of Mallik’s research is understanding how very tiny proteins, called ‘motor proteins’, function within cells. These proteins can be compared to tiny machines at nanoscales — their function is to transport other material from one location to another, all within one cell.
A living cell consists of several organelles, each of which is akin to sub-compartments that perform specialised functions, much like a factory. A product of these functions is often material that needs to be moved from one part of the cell to another. This material is carried like cargo is carried from one factory to another on a predetermined track.
These motor proteins generate forces that are millions of times smaller than the forces human beings can detect. They are present in all the different types of the cells in the body.
When a bacterial pathogen infects the body, it is the job of these motor proteins to carry each bacterium they encounter inside a cell to the lysosome of the cell. Lysosomes function as an execution chamber of sorts, where the pathogen is taken to be ‘degraded’ and destroyed, thus preventing infections. When motor proteins fail to do their job, pathogens multiply and cause infections.
It isn’t just bacteria that these proteins carry; they also transport blobs of fat to convert them into something called low-density lipoproteins. This process occurs inside liver cells, called hepatocytes. The liver is the primary organ when it comes to fat regulation in the body.
Understanding how pathogens hijack motor proteins’ processes and what inhibits motor proteins from doing their work of carrying bacteria or fat cells is crucial to understanding and tackling diseases of all kinds.
Studying these motor proteins at such small scales can be very tricky. To observe how much force they generate and how their momentum is impacted, Mallik’s lab uses a technique called optical trapping.
“A fat particle that is one micron is size has a different refractive index as compared to water,” explained Mallik. “Refractive index is what makes material bend light in a different manner when it passes from one material to another.”
This is famously demonstrated by a bent straw placed in a glass of water: As light travels from air to water, it encounters a change in refractive index, and thus appears to bend the straw.
When a beam of laser is shone on a bacterium or a fat particle, light bends again due to the change in refractive index. And when light bends, there is change in its momentum, as photons move slower. According to Newton’s third law, an equal and opposite force is then generated.
“When the momentum of the photon changes, the photon applies a little kick to the particle, whether it be a fat ball or a bacterium. And therefore, by using a shiny light on these particles, we can apply a force on them,” said Mallik.
These forces that are generated using such an optical trap are similar in magnitude to the kind of tiny forces that these motor proteins generate. By measuring the change in these forces across different stages, their mechanisms of functioning and inhibition can be better understood.
“When a bacterium enters your immune cell, the force exerted by motor proteins can be less,” elaborated Mallik.
“But after some time, when the bacterium is able to hijack the motor protein, the force can be higher. Therefore, we can directly measure the activity of these motor proteins by optical trapping, and then, we can then use this to find out how pathogens may hijack motor protein and which motor is hijacked.”
Mallik’s lab used this mechanism to study and understand Leishmania, the parasite that causes leishmaniasis, also called Kala Azar, which affects over 1 million people worldwide.
The same principle applies to lipids as fat particles are being transported inside liver cells. Mallik’s lab seeks to answer questions such as how many motors are transporting fat particles, how this changes depending on whether an individual has had food, how it is affected by diseases, and more.
Future of the research
Mallik’s lab has currently worked mostly on cell cultures and on rats.
“Our research is still at a basic stage, and eventually, we hope to be able to apply this on patients as well,” he said.
Mallik’s research also holds relevance to Hepatitis C. The virus that causes this infection uses fat to multiply inside the liver, by occupying the surface of fat particles. By sitting on top of fat particles, it takes away the energy stored in fat, used by the body’s metabolic processes, and uses it to multiply instead.
“We were able to inhibit this absorption of energy by preventing the interaction of the virus with fat particles,” said Mallik promisingly.
This report was edited to correct a typo