As is fairly well known, DNA, or deoxyribonucleic acid, contains all the genetic information about an organism. It is this information that decides external as well as internal characteristics of an organism. Abrupt changes in the genetic composition can induce permanent and irreversible changes in the organism, leading to disease or even death. For this reason, maintaining the “integrity” of the genome, which refers to the entire set of genetic material in an organism, is paramount.
However, there are times when modifications in the genetic information are actually favourable. When an organism such as a bacterium encounters an adverse environment, it has to adapt. Over time, changes accumulate in its genetic information in a way that reduces the stress it feels in the new environment. Genomic modifications are therefore necessary for evolution. No changes in the genome would mean no evolution.
Again, organisms are endowed with another set of molecules that facilitate changes in the genome under adverse circumstances.
The genome of every organism is under constant influence of these two parallel, but mutually opposite, mechanisms. The interplay of the two seemingly conflicting set of molecules ensures that the organisms have the ability to adapt without compromising the integrity of their genomes.
For over ten years now, Deepak T Nair and his team at the Regional Centre for Biotechnology in Faridabad have been studying the behaviour of different sets of molecules that are known to either facilitate or resist the changes occurring in the genome of bacteria and viruses. The endeavour of Nair, a structural biologist, has been to understand the mechanisms behind the functions of these molecules.
For example, Nair’s team had been trying to find out why certain bacteria mutate at a faster rate in human bodies to gain resistance to antibiotics. One particular molecule in the bacteria was known to get activated in an adverse environment and increase the frequency of mutations in the bacteria. Nair and his team were able to find the mechanism utilised by this molecule to enhance the rate at which mutations appear in the bacteria. He has been able to figure out what exactly is special about this particular molecule and the mechanism by which it achieves calibrated mutagenesis.
The next step is to find ways to somehow inhibit this evolutionary apparatus in the bacteria, so that its ability to gain resistance against antibiotics is thwarted. Such a successful intervention would result in increased effectiveness of existing antibiotics.
Nair’s research has also resolved, through experimental validation, recent questions over the mechanism by which the bactericidal antibiotics work on the bacteria. The results of his experiments have conclusively shown that these antibiotics do indeed, as was recently proposed, trigger the activation of reactive chemicals known as Reactive Oxygen Species and these chemicals contribute significantly to the death of bacterial cells.
In another significant breakthrough, Nair has been able to show what exactly happens at the beginning of genome duplication process in the case of Japanese encephalitis virus, that is transmitted by mosquitoes and is a major killer, especially of children, in North India. Nair’s work has shown that how a molecule known as ‘GTP’ helps in the accurate initiation of the genome duplication process in Japanese encephalitis virus. Targeted inhibition of the interaction between GTP and the duplication machinery can be used to develop new drugs against JEV.
For this, and many of his related research works, Nair was recently selected for the prestigious Shanti Swarup Bhatnagar Prize for 2017.