Researchers find cholesterol link to tackle drug resistance

By T V Venkateswaran and Bhavya Khullar

New Delhi: Even as research and development in the field of medicine is bringing in newer services and products, the health sector is also facing a major problem in the form of growing drug resistance.

New resistance mechanisms are emerging and spreading globally, threatening the ability to treat common infectious diseases and thus resulting in prolonged illness, disability and death.

Governments and the industry are pouring in huge sums of money to solve the problem and scientific institutions and scientists are making all out efforts to find solutions.

India is at the forefront of such efforts. Scientists at the Council of Scientific and Industrial Research (CSIR’s) Centre for Cellular and Molecular Biology (CCMB)  at Hyderabad have come out with a finding that promises to offer a lasting solution.

A team of CCMB researchers led by J.C.Bose Fellow, Prof. Amitabha Chattopadhyay have recently found that the entry of disease-causing microbes into human cells can be cut down significantly by reducing the level of cholesterol that is available on cell membranes.

In other words, one can reduce the burden of diseases, which depend on the entry of the microbe into blood cells to establish infection and at the same time combat the problem of drug resistance by merely reducing the cholesterol content on the cell membrane.

Explaining Dr Chattopadhyay noted that microbes become drug resistance through the process of mutation mainly because the drugs that are presently used to kill them attack their DNA. If, instead, the focus was on stopping the microbes from entering the cells by reducing the cholesterol level on the cell membrane there will be less possibility for the microbes to mutate and thus develop drug resistance.

He further stated that more studies would be required before a drug or a treatment process based on the new finding could be developed. Their work holds great promise given that old drugs developed to combat infectious diseases like TB are becoming toothless and discovering alternative antibiotics are not that easy.

His team was the first in the world to show how Cholesterol molecules on cell membrane interacted with a special class of cell membrane proteins called G-Protein coupled receptors or GPCRs, which control the body’s response to a wide variety of signals including drugs, toxins, and microbes. These proteins sit on the cell membrane, which separates the cell from the outer environment and at the same time helps them communicate. They showed that Cholesterol binds to GPCRs at specific sites, alters their conformation, and affects their function.  This could be exploited develop new class of drugs to combat infections diseases.

They also made another fascinating discovery.  They found that water has a restricted movement inside the cell, which is different from the sloshing it experiences in an open vessel, and this feature is vital to maintain the function of cellular GPCRs. The movement of water molecules is lesser because cells are a few nanometers in dimension. This nanoscale confinement exerts a combination of forces on water molecules that changes their physical properties without affecting its chemistry. This unique blend of newer physical and chemical properties of water is the driver of its function inside the cell.

CCMB has a special place in the history of Indian science in general and CSIR in particular. It is the first national laboratory to be established  in the field of biology. Until 1976, when it was set up, India had national institutions for physical and chemical sciences only.

The institute grew up very fast and apart from research and development it was in the forefront in promoting collaboration with the industry. It achieved early success in 1992, when it produced the first recombinant hepatitis virus in association with Hyderabad based Shanta Biotech.

The institute is known for offering interdisciplinary studies with faculties from diverse fields including mathematics, chemistry, and engineering, in addition to biology. Students from all over the country, including small towns and villages, pursue research here.

“We had a record turnout on campus open house day last year when 12,000 people visited the Institute and got to know about the work being done in the various laboratories”, said Prof Chattopadhyay.

Asked what drove him to science, he went back in time and narrated “the beautiful relationship’’ he had with his father. `My father was a major in chemistry even in those days. He motivated me to pursue science’’.

He is a chemist by training. But his works are mostly in biology. A PhD from IIT-Kanpur, he joined postdoctoral research in chemistry at State University of New York at Stony Brook, but soon migrated to University of California at Davis as he got interested in biology.

“Most of my awards are in biology and I don’t have a formal education in this field”, he laughs. Citing his own example, he emphasizes that students should pursue what they love and not limit themselves. (India Science Wire)