India Alliance Fellow Spotlight: Amit Singh, IISc, Bengaluru

24 Mar 2020

India Alliance Fellow Spotlight: Amit Singh, IISc, Bengaluru


"To meet the reality of eliminating TB from India by 2025, efforts should be made to build a robust ecosystem to empower basic research and close the gaps between fundamental research and clinical problems such as diagnostics, inadequate treatment, and drug-resistant infections."  India Alliance Fellow at IISc, Bengaluru, Amit Singh who is studying difficult-to-treat drug-resistant TB infections, shares his wish on World TB Day 2020, offers tips for aspiring India Alliance Fellowship applicants and more in this 'Fellow in Spotlight' feature. 

Please tell us what you are working on and what impact do you hope it will have.

Tuberculosis (TB) kills ~ 1000 people every day in India. Globally, 1.8 million people died due to TB in 2018 alone. Mycobacterium tuberculosis (Mtb-causative agent of TB) has evaded drugs and vaccines pointed at it by the scientific community, making it the most feared global pathogen. The exceptional ability of this bacterium to enter into a phase of “persistence” despite a robust immune response has allowed this pathogen to linger for decades humans. In this state, the TB bacteria are tolerant to multiple antibiotics, which led humankind to suffer months to years of specialized drugs to achieve treatment cure from TB. This protracted treatment invariably leads to non-compliance due to the toxicity of these drugs and various side effects, further fueling the development of difficult-to-treat drug-resistant TB infections. The physiological and molecular basis of this state of drug-tolerant “persistence” is barely understood, thanks to a shortage of fundamental tools to unravel bacterial physiology, making it the proverbial holy grail of research on TB. It is this challenging and important area of research that our group has taken head-on in our pursuit of science. In doing so, we have successfully developed cutting-edge technologies to probe bacterial physiology and identified mechanisms of persistence and therapy failure during TB infection. We integrated our basic findings with translational research and discovered that approved antimalarial drug chloroquine potentiated the efficacy of current anti-TB drugs to accelerate the elimination of TB.

24th March is World TB Day. What is on your wish list this year, as someone studying this disease?

Based on the Global TB Report 2019 of the WHO, India has the highest number of TB and drug-resistant TB cases in the world. It is clear that TB rates are not falling fast enough, indicating that progress is too slow to manage TB and meet the targets. Despite the fact that 1000 people die of TB every day in India, this disturbing rate of endless mortality neither becomes news nor translates into a mass movement, whereas one case of COVID-19 attracts political, societal, pharmaceutical, and scientific attention. In current settings, one gains the impression that there is a political will and possibly a strong strategy. However, rather than grand pronouncements and the rhetoric that may never meet the reality of eliminating TB from India by 2025, efforts should be made to build a robust ecosystem to empower basic research and close the gaps between fundamental research and clinical problems such as diagnostics, inadequate treatment, and drug-resistant infections. Moreover, pan-India engagement of research institutes with TB hospitals and pharma community is needed to accelerate research in the areas challenging TB management.

A Pennsylvania State tuberculosis clinic: a male doctor is shown examining the tongue of a young boy, while a female medical practitioner takes the pulse of a woman. Photograph, 1925/1935? Credit: Wellcome Collection (CC BY 4.0)

Is there a research area other than yours that interests you deeply and that you would like to perhaps integrate in your current research?

It is increasingly clear that during infection, the human host employs a nutritional immune response that limits the availability of metals such as iron and zinc to prevent bacterial growth. Multiple mechanisms that the host exploits to hinder the availability of metals to pathogens and how pathogens counteract this strategy to successfully establish infection remains poorly understood. The strong association between metal homeostasis and immune mechanisms underlie several disease pathologies. Our group is deeply interested and committed to understanding the interplay of metals in host-pathogen interaction. Because the conventional antibiotics are largely inadequate and the emergence of multi-drug resistance is a major threat; understanding and targeting mechanisms exploited by pathogens to overcome nutritional immune pressures represent important areas of research.

How has the India Alliance fellowship helped you achieve your goals as a biomedical researcher? Any tips for aspiring applicants?

Research involving BSL3-class human pathogens is not only technologically challenging but also a significant drain on funds. I am saying this without any hesitation that the India Alliance is the only funding agency, which whole-heartedly supports the financial aspirations of researchers in India. The flexibility built in the fellowship promotes innovation and puts one on a trajectory where they are poised to be successful. Annual meetings organized by the India Alliance are the perfect outlet platform to showcase our findings and to network. Moreover, I personally benefited from attending various India alliance supported workshops such as EMBO leadership training programs and clinical research meetings. In sum, the India Alliance supports the overall development of your career as a biomedical researcher, and improve your mentoring, and leadership skills. Aspiring applicants need to think of an important fundamental biomedical problem that represents a major knowledge gap in the field. The key is to develop a scientifically sound proposal matching international standards (NIH, EMBO, BBSRC, etc). It is advisable that applicants discuss their proposal with the subject experts before finalizing the application.

What is it about your work that keeps you going every day?

Engaging, teaching and mentoring young students are most gratifying. I am always on the lookout for new technologies that can speed up research in the TB field. We thrive on continuously upgrading toolkit to peek inside the TB bacteria that reveals surprises unique to this pathogen. Due to genetic intractability, most of our efforts are unsuccessful in understanding TB bacteria. Occasionally we get success, the taste of triumph (even modest!) after a long haul is what keeps the fire going within.

Next to academic research, what do you enjoy doing the most?

I mostly unwind by reading books, playing badminton, movies, and cooking.