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Understanding how mistakes made while manufacturing proteins can be good

Dr Laasya Samhita, Assistant Professor of Biology at Ashoka University, elaborates on her research that aims to unravel molecular mechanisms linking translational errors and antimicrobial resistance

Yukti Arora

14 September, 2022 | 6m read

Let’s start by talking about your research journey so far:

I sometimes think that biology was ‘the most boring subject’ taught in school, concentrating on drawing skills and mugging up various terms, with no real introduction to the subject at all. Other than exposure at home, the IISc (Indian Institute of Science) Young Fellowship and the Kishore Vaigyanik Protsahan Yojana (KVPY) were critical to my scientific growth.

After my Bachelor’s degree, I joined the Integrated Ph.D. program in Biological Sciences at IISc. Both during my Ph.D. and postdoctoral work as a DBT/Wellcome Trust India Alliance early career fellow, I was exposed to rigorous scientific training and a stimulating atmosphere of constant discussion.

You have been working extensively on mistranslation. What is the relevance and larger objective of this research?

I work at the interface of molecular biology and evolution. I try to understand how mistakes made while manufacturing proteins can affect cellular function. Specifically, work from my lab will try to understand how such errors contribute to survival in different environments, and in particular to antibiotic resistance in bacteria. We hope to start systematic mapping of environmental antibiotic resistance by surveying water samples from rivers.

Over time and with collaborations, this should help us link data from three real-world settings which often remain disconnected: the lab, the clinic, and the environment. It would also expand our understanding of the phenomena that lead to antibiotic resistance.

While we understand how DNA-based changes are transmitted across generations, the impact of protein-based changes on evolution remains poorly understood. Proteins are biomolecules responsible for carrying out most cellular functions, and their sequence and function is therefore very important to the cell. Mistakes made during the synthesis of proteins (mistranslation) lead to altered proteins, which are most often harmful but can also be beneficial when the cell is under stress.

Even though these altered proteins (unlike mutated DNA) cannot be transmitted to the next generation, mistranslation can impact several critical cellular functions including how genes are expressed, how fast they mutate, and various forms of stress resistance including resistance to antibiotics. From a fundamental science point of view, exploring information flow from protein to DNA (rather than DNA to protein) leads to an exciting new arena.

Antibiotic resistance is anticipated to be the next pandemic. Does mistranslation in microbes affect their resistance to antibiotics? What impact of this research do you envision?

From a human perspective, mistranslation-based changes in disease-causing microbes can cause serious health issues by making the microbes more antibiotic-resistant. By exploring such phenomena, I hope to expand our understanding of how such changes can impact evolution and also affect real-world problems such as antibiotic resistance.

In today’s post-pandemic atmosphere, we are all acutely aware that pathogens adapt in unexpected ways. Translation errors help organisms to exceed the coding capacity of their genomes and throw up a variety of novel phenotypes (observable physical properties of an organism), some of which are stable across generations and may contribute to virulence.

As technical advances facilitate a better understanding of molecular mechanisms in this nascent field, I am confident that we will understand and combat bacterial stress tolerance, and hence infections more efficiently. In the future, I hope that work from my lab can drive novel and diverse drug designs and help combat the global health problem of AMR.

Exploring the evolutionary impact of mistranslation is relatively a new area of research. What are the key technical/non-technical challenges that you may encounter?

There are several technical challenges. Matching a change in phenotype of an organism with one or more altered proteins is one. Disentangling genetic from epigenetic contributions to adaptation is another.

From the point of view of measuring non-genetic resistance to antibiotics, non-genetic resistance can arise in several ways; and there is no technique available for an overall identification and quantitative estimation of such phenotypes. The paucity of long-term data for clinical as well as environmental resistance trends means that correlating clinical with environmental and laboratory resistance remains a challenge. This is a roadblock that we hope to address in our work at least in part.

On a non-technical front as well, there are problems. The systems that support independent science researchers do not make it easy for anyone beyond a certain age. The age limits for applying to postdoctoral grants as well as during hiring is a hurdle for everyone, but it becomes increasingly difficult for women who have maternity-related breaks. There are now grants that specifically account for career breaks and give age concessions to women, and this is great, but the (often unstated) age rule during hiring at an early stage in your career can be very discouraging.

How will Ashoka help you in your professional journey and why did you choose to work at Ashoka?

Ashoka University has a diverse set of accomplished biologists whom I hope to learn from and collaborate with. I think one big plus about this institution has been its focus on independent thinking and experience rather than age limits.

My impression is that the University is driven towards investing in people as individuals. This creates a low-stress and supportive atmosphere, making it easier to discuss concerns regarding work-life balance. The flexible atmosphere, support for other daily activities, and generous funding nurture a creative space that I find quite unique in today’s science ecosystem in India.

(Edited by Ms Saman Waheed. She is currently an Assistant Manager at the Office of PR & Communications, Ashoka University.)

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