Bio Patrika interviews Dr. Chakrabarti on her thoughts about “injury mediated training of the innate immune system”

Dr. Sveta Chakrabarti’s interview with Bio Patrika hosting “Vigyan Patrika”, a series of author interviews. Dr. Chakrabarti is currently working as an India Alliance (Wellcome/DBT) Postdoctoral Fellow in Prof. Sandhya S. Visweswariah at the Department of Molecular Reproduction, Development, and Genetics, Indian Institute of Science, Bangalore. Dr. Chakrabarti published a paper entitled “Intramacrophage ROS Primes the Innate Immune System via JAK/STAT and Toll Activation” as a first and senior author in Cell Reports journal (2020).

How would you explain your paper’s key results to the non-scientific community?

My work has revealed that hydrogen peroxide produced from a wound activates specific signalling pathways in the fruit flies’ blood cells (also called hemocytes). Hydrogen peroxide acts as a danger signal to help home in hemocytes to the site of damage and activate wound-healing responses. Hemocytes, in turn, help produce more hydrogen peroxide near the wound using an enzyme called DUOX. Interestingly, we found that a water channel called aquaporin helps build up hydrogen peroxide in blood cells following an injury, critical for their activation. Interestingly the immune response called the Toll pathway that fights and kills bacteria was activated upon injury. We then found that the Toll response protects flies from subsequent infection by bacteria. Our results point to the role of injury training the immune response to fight a future potential pathogen.

Our discovery points to the innate immune system’s capacity to keep the memory of an attack, albeit a simple injury. On a subsequent challenge, these immune cells mount a more significant response. In simple terms, this is like sending in spies to know that you may be under attack soon by an enemy like a pathogen. You then prepare yourself by stocking ammunition and conducting drills with those such that when the real threat appears, you are ready to eliminate them.

Figure 1. The responses mounted by immune cells after either infection with bacteria or damage like an injury (shown on the right). Fly blood cells are marked in green in the fly shown on the bottom right panel.

“Our discovery points to the innate immune system having the capacity to keep the memory of an attack, albeit a simple injury.”

What are the possible consequences of these findings for your research area?

The identification of hydrogen peroxide, which is usually associated with killing cells as a molecule that signals blood cells to migrate to a wound and activate inflammation, is exciting. It also seems like an intracellular build-up in H2O2 is required to activate hemocytes after an injury. In the following study, we plan to follow aquaporin loss of function or knock down hemocytes to check if this water channel has additional roles in hemocyte migration after wounding. Drosophila adult hemocytes will serve as a useful model to explore molecular mechanisms of how a ROS burst after an injury impacts signalling in blood cells and how modulators like aquaporins impinge on this response.

Figure 2. Model of the ROS burst after wounding that activated hemocytes. The main players are shown in the cartoon of the hemocyte, and below is the idea of immune training.

What was the exciting moment (eureka moment) during your research?

The ‘eureka’ moment for me in carrying out this study was realizing that a simple wound can have such impressive consequences in flies’ life history. The so-called ‘immune memory’ can protect them from a subsequent attack from a pathogen.

What do you hope to do next?

I am currently working on the innate immune pathway called JAK-STAT that contributes to survival to wounding and bacterial infection. Our previous study showed that injury-induced cytokines production called unpaired proteins by hemocytes, which then activate the JAK/STAT pathway in the fat body and the gut. One of the most surprising findings of that study was that release of unpaired-3 from hemocytes can stimulate intestinal stem cell proliferation. This was an unexpected interaction between hemocytes and intestinal stem cells. I am following up on how hemocytes might be migrating to the gut after a distant injury and subsequently changing the gut’s physiology to improve fly survival.

Where do you seek scientific inspiration?

I would say my motivation to do science lies with the fact that I was always curious about the natural world from a young age. I was passionate about helping people with diseases, and as I reached high school, I realized it was scientists who discovered cures rather than a medical doctor. I am very passionate about biology and I hope this stays with me in the years to come.

How do you intend to help Indian science improve?

I hope to bring my research more accessible to the general audience, especially in schools and colleges, to inspire the coming generation to take up science. I am keen to show young girls that a career as a scientist can be fun and does not necessarily mean losing out on private life. I hope to serve as an example that one can come back from a developed country like Swiss and pursue exciting science in their homeland without a compromise in the quality of their work.

Reference

Chakrabarti S*, Visweswariah S S. Intramacrophage ROS Primes the Innate Immune System via JAK/STAT and Toll Activation. Cell Reports, 33, 108368.

Author introduction and research interests

Dr. Sveta Chakrabarti is working as an India Alliance (Wellcome/DBT) Postdoctoral Fellow in Prof. Sandhya S. Visweswariah at the Department of Molecular Reproduction, Development, and Genetics, Indian Institute of Science, Bangalore. Sveta completed her Ph.D. in Life Sciences at the École Polytechnique Fédérale de Lausanne (EPFL), followed by a year-long post-doctoral fellowship. She is trying to understand the mechanisms of JAK/STAT signaling towards wound healing and immunity. Due to the significant implication of this research to immunology and wound healing in mammals, in particular humans, it may help bring our understanding to develop therapeutics where this process is misregulated like autoimmune diseases.

Email: svetac@iisc.ac.in

Learn more about Prof. Sandhya S. Visweswariah lab research interest’s https://mrdg.iisc.ac.in/sandhya/index.htm

One thought on “Bio Patrika interviews Dr. Chakrabarti on her thoughts about “injury mediated training of the innate immune system”

  1. Nice thoughts from a women scientist. Even though I think it is not just about having or not having a private life that dissuades women from pursuing science or any other demanding career. Passion, financial constraints and aptitude are also equal if not more important factors to pursue any field.

    Liked by 1 person

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