Understanding the role of master regulators

Published in The Hindu on July 27, 2006

After obtaining a B. Tech from the Centre for Biotechnology at Anna University, Chennai, M. Madan Babu headed straight for the Medical Research Council’s Laboratory of Molecular Biology (LMB) at the University of Cambridge, U.K., for a Ph.D programme. He earned his doctorate in just three years.

His next destination was the National Center for Biotechnology Information, which is part of the National Institutes of Health, Maryland, U.S. After a year and a half, 26-year-old Babu, a Max Perutz prize winner, is back at LMB as a group leader raring to make a mark in a field which he has worked in for the last five years – systems biology. Science Editor, R. Prasad interviews him

Systems biology is a relatively new field, so how did you get interested in this area of research?

Basically, it was the summer project that I did during the first year of B.Tech under the guidance of Professor P. Balaram, who is now the Director of the Indian Institute of Science, Bangalore, which motivated me to get into this field.

Your Ph.D was in computational biology. When did you change over to systems biology?

Systems biology is a part of computational biology. I eventually got interested in systems biology during the Ph.D programme.

Did you realise that the field was new and you were taking a risk?

Yes, I did. That is the thrill of research; the thrill of taking risks.

What made you return to the Medical Research Council and not continue at the National Center for Biotechnology Information?

The primary reason was that the MRC is very much open to new ideas and novel directions, which several other established institutions would consider too risky to venture into. It has an informal atmosphere and the accomplished scientists, including the Nobel Laureate Aarom Klug, working there are always available for discussions. And lots of discoveries come up during such discussions. MRC provides a conducive environment for creative people to excel in. And unlike in the U.S., there is no pressure to publish in reputed journals and people are seen not as competitors but as individuals. More importantly, it encourages basic research that may take a long time to produce results, if at all.

What were you working on during your Ph.D programme?

I was primarily trying to understand the transcriptional regulation in biological systems; to understand the evolution of gene regulation.

Can you elaborate on this?

Genes get transcripted to mRNA, and the mRNA, in turn, gets automatically translated into proteins. A lot of regulation is required to produce mRNA because the production of mRNA consumes substantial energy. And you don’t want mRNA to be produced if the protein is not required in the first place. Not all proteins are required at all times. That is the basis of transcriptional regulation. So the point is to produce the right protein at the right time. The primary problem that I addressed was in understanding how regulatory systems evolved; and to know the players and how these players evolved.

What was the outcome of your work?

My advisor, Dr. Sarah Teichmann, and I found that a few players [transcriptional regulators] decide the production of several proteins while there are many who decide the production of a few proteins. So essentially, 80 per cent of the decisions are taken by 20 per cent of the regulators. These [20 per cent] regulators are the master regulators. This is what we see in any organisation or institution, not just in microbes – a few key players taking most of the key decisions.

And what about your post-doctoral work at NCBI?

I primarily continued with what I was doing during my Ph.D. – studying the organisation and evolution of transcriptional networks. My advisor, Dr. L. Aravind, and I identified the factors that shape the structure of the transcriptional network in 174 organisms living in more than 40 different environments. The main finding was that environment shapes the structure of transcriptional network. This is similar to what is seen in the organisation structure of any company and the differences you see in companies of different industries such as newspaper and manufacturing industries.

What are the potential applications of your work?

We can engineer microbes in a more rational way. For instance, if we know the pattern of interactions between proteins, we can either knock off or introduce a new interaction to increase the production of particular proteins. Pharmaceutical companies that use fermentation technology can use this to increase the production of molecules of interest.In the case of pathogens, if we can knock off the master regulators, we can essentially cripple the system; we can completely destroy the organisms. So, the point is to look out for the most important link to destroy the [pathogen’s] system.

Which areas will you focus on as a group leader at LMB?

I intend focusing on understanding the regulation of cell size; the cell to cell communication; and finally the cellular morphology/differentiation.

How big is your group?

To start with, there will be one Ph.D student and one post-doc and a research programmer. I will be the advisor for the Ph.D student and post-doc.

How many papers have you published in scientific journals?

Twenty-seven papers in all; three more are in the press. I had published four during my B.Tech programme, 12 during my Ph.D, and 11 during post-doc.

Are there researchers in India working in this field?

People here are still working on individual or groups of proteins and not looking at it from a larger perspective. But their results are important and will be of great use when we try to piece the puzzle together.

Do you intend returning to India at any time in the future?

Yes, I will come back. It is difficult to say when, but I want to come back … I will stay back there till the field is developed.

Posted in Uncategorized