Sanket Nagarkar, a PhD student working with Prof. Shashidhara, studying tissue growth in tiny insects

When I joined Ashoka full time on 3 July 2019, I had little idea that I would be spending more time away from the campus than on campus. As Dean of Research, I was expecting to remain on campus, even during vacation. But that changed due to unforeseen circumstances. First, we had severe air pollution forcing us to close the University for two weeks and then a once-in-a-century-like pandemic struck us, and we are still in the middle of this crisis.

My research lies in the area of experimental biology. A specific question we are trying to answer is how organ/tissue size and shape are determined early during embryonic development. For example, how is it that all of us have arms that are of the same size, proportionate to our body? Recently, we had some interesting findings which connected growth control during early embryonic development to a fundamental molecular machinery that is present in all our cells. As we know, genetic information is encoded in DNA. This is encoded in a specific language (of nucleotides), wherein the information is to make certain proteins (the language here is of amino acids), which in turn carry out specific biological functions. Genetic information is decoded through a two-step mechanism – from DNA to RNA (a process known as transcription) and RNA to protein (a process known as translation).

An important reason life has flourished on Earth for over 3.5 billion years and so many diverse and complex organisms have evolved is the elaborate regulatory mechanism that ensures that no gene is decoded, or corresponding proteins made unless strictly required. This ensures that biological systems are energy efficient and make fewer mistakes. It is a matter of pride that amongst the advisors to Ashoka’s biology programme, we have two Nobel laureates. Prof. Jack Szostak works on the fundamental question on the origin of this system of coding and decoding genetic information. Prof. Venki Ramakrishnan works on the translation of genetic information to make proteins in ribosomes.

Returning to our work, we have discovered that an important step in growth control is limiting the transcription of those genes that, otherwise, enhance cell division. This interesting control system functions like traffic lights. When a gene is

decoded, the transcription is initiated and then paused. A green signal is shown if all aspects of the cellular system are working well, only then the transcription proceeds until the end. We have shown that it is when these genes bypass the above-mentioned rate limiting step, corresponding proteins are made in larger quantities leading to cancerous growths.

There are two major benefits of such a regulatory step. One, it ensures that cells divide a specific number of times and thereby help organs/tissues attain a specific size. Otherwise, the body cannot function efficiently. Second, due to multiple regulatory steps that occur later in adult stem cells, there are far less chances of these growth-promoting genes getting precociously activated. Otherwise, we would have had cancer all the time, and all over the body.

What is even more fascinating is that our original discovery of this growth regulatory mechanism was through examining fruit fly insects as the experimental model – and the results are applicable to human biology!

We are currently exploring if mis-regulation of this ‘pausing’ step during the transcription of genetic information could be used as a prognostic marker to predict the long-term outcome of the cancer. As labs are shut due to the pandemic, students are using the internet to meta-analyse published data to look for any clues in this direction. Preliminary analysis suggests poor prognosis of certain epithelial cancers (colon, breast, etc.) when growth-promoting genes do not pause during their transcription.

While progress in our experimental research is considerably slowed down due to the global pandemic, remarkably, teaching and other academic activities continue uninterrupted. Ashoka has fantastic academic and IT teams to ensure that online teaching is as effective as physical classroom teaching. The number of emails exchanged to address the problems, real and imaginary, that students may be facing while learning online were amazing. All those were systematically analysed and then solutions were identified and deployed immediately. Quality, efficiency, timely decisions and their implementation after consensus – these are the hallmarks of a great University in the making. I am glad to be a part of this community.

L.S. Shashidhara is Dean of Research and Professor of Biology. His primary areas of focus are genetics, molecular biology and evolutionary biology.