Detecting identification marks on pathogens

Work done in the lab of Prof Anirban Banerjee at Indian Institute of Technology Bombay (IITB)

About author

Shruti Apte: Shruti Apte graduated from Goa University before moving to Savitribai Phule Pune University to complete her master’s degree in Microbiology. In 2017, she joined IIT Bombay to pursue her doctoral studies under the guidance of Prof. Anirban Banerjee. Her doctoral work focused on understanding the pathogenesis of Streptococcus pneumoniae. Shruti is interested in gaining expertise in the field of Host-Pathogen Interaction and Cellular Immunity.

Sourav Ghosh: Sourav Ghosh was born and raised in Kolkata, “The City of Joy.” He completed his Bachelor’s from Vidyasagar College and Master’s from the University of Calcutta in Biochemistry. In 2019, he joined the Bacterial Pathogenesis lab at IIT Bombay under Prof. Anirban Banerjee. He is interested in exploring the different aspects of cellular immunity in eukaryotic cells. In his spare time, he loves watching football and playing the guitar.

Smita Bhutda: Dr. Smita Bhutda received her B.Sc. (2010) and M.Sc. (2011) in Biotechnology from the University of Mumbai, India. She then joined the National Institute of Research in Reproductive Health (NIRRH-ICMR), Mumbai, India, where she held the position of junior research fellow. Her study was focused on investigating stem cells in the adult mouse ovary, the effect of chemotherapy on stem cells, and their potential to differentiate to regain ovarian function. She received her PhD (2021) in cellular microbiology from the Indian Institute of Technology Bombay, India. Her PhD work was focused on understanding a universal approach of bacterial ubiquitination for sensing diverse intracellular pathogens. Currently, she is working as a postdoctoral fellow with Dr. Roger Greenberg at the University of Pennsylvania (UPenn), USA, in the Department of Cancer Biology. Smita is looking into Homologous Repair (HR) for double-stranded DNA (dsDNA) breaks at the molecular level, with emphasis on disassembly of NHEJ protein complexes.

Interview

How would you explain your research outcomes to the non-scientific community?

By using infection-causing bacteria, we find that our immune system identifies “common patterns” present on them. These common patterns are then flagged as danger signals to the system, which pushes them towards clearance. When common patterns are deleted from the germs, they become even more fatal, indicating the importance of this feature in protecting us from infection. To summarize, we identify a common principle repurposed by our system to locate and flag common eukaryotic-like features present in pathogens, which protects our body from infections.

How do these findings contribute to your research area?

Given the variety of pathogens we encounter, identifying certain common features in different germs would be a smart strategy for resource optimization. Unveiling this system has paved the way for new therapeutic practices where one’s immune system can be boosted by supplying such common patterns, similar to vaccines, to identify pathogens efficiently as and when they are encountered. With the growing advent of antibiotic resistance in microbes, harnessing immune defense with host-directed therapy could serve as an effective regimen. Importantly, these findings shed light on understanding the rudimentary cellular immune processes, which could be harnessed to intensify antibacterial immunity.

What was the exciting moment during your research?

Shruti Apte: There are two such moments which I can vividly remember right now. The first one happened around my third year. At that time, every cloning associate with this project was stuck due to some reason or other. I struggled with one particular clone for more than a year! At this time, COVID-19 struck the world and we had to abandon our work. After returning back, I began with this cloning to give it a final try and voila! The clone came positive! The second incident happened when I was trying to perform one of the final experiments. It was a critical in-vitro experiment. However, the experiment kept failing multiple times until I was left with very little chemical resource required for running the experiment. Just when I was about to lose hope, the reaction worked! I was relieved and happy at the same time!

Sourav Ghosh: There were many exciting moments for me. One was when we prepared the samples all night and then traveled to Pune with Dr. Smita (Co-author) to capture our first super-resolution imaging of the bacteria inside human cells. Another was when we could not express a bacterial protein in a mammalian system, and we were stuck for two months. Finally, one night, I observed the cell pellet to be green as my protein was tagged with GFP. I immediately called my PI to let him know, and he was delighted. That day I concluded my experiments only after 10 pm.

Smita Bhutda: This research journey was an emotional roller coaster with many exciting moments with every research progress. However, the most exciting moment for me was when our first experimental result on protein ubiquitin substrate was corroborated with our bioinformatic model. This proved our scientific hypothesis and gave us confidence to follow this problem deeply. Also, performing super resolution confocal microscopy was the second most exciting moment during this research.

“These findings shed light on understanding the rudimentary cellular immune processes, which could be harnessed to intensify antibacterial immunity.”

What do you hope to do next?

The lab is currently working on multiple offshoot projects that arose from this finding. We are keen to understand the consequences of this process and study in depth the process of pathogenic clearance in the host cell.

Where do you seek scientific inspiration from?

Shruti Apte: Seeing the constant drive to learn and seek something new around me is a key source of inspiration to me.

Sourav Ghosh: Our current work was extremely challenging, and we faced multiple roadblocks. However, the difficulty of the project allowed us to evolve and helped us to adopt unique tactics to resolve the problems. Our group showed phenomenal teamwork that was different from our previous scientific ventures. This unique experience inspired me.

Smita Bhutda: My curiosity to understand everything in depth and my aim to do something impactful for society inspires me to do research.

How do you intend to help Indian science improve?

India surely has a rich pool of scientific minds to conduct quality science. Therefore, in the future, I would like to fuel the innovative and inquisitive thinking in students. Importantly, I have realized the importance of collaboration in science, and thus I would promote such collaborations at any stage of my career. Simultaneously, I believe that supporting and encouraging women scientists in India is a need to foster inclusive research.

Reference

Apte S, Bhutda S, Ghosh S, Sharma K, Barton TE, Dibyachintan S, Sahay O, Roy S, Sinha AR, Adicherla H, Rakshit J, Tang S, Datey A, Santra S, Joseph J, Sasidharan S, Hammerschmidt S, Chakravortty D, Oggioni MR, Santra MK, Neill DR, Banerjee A. An innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins. Sci Adv. 2023 Mar 22;9(12):eade1851. doi: 10.1126/sciadv.ade1851. https://www.science.org/doi/10.1126/sciadv.ade1851

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Pragya Gupta

PhD Scholar, University of Melbourne, Australia

Beside being a passionate stem cell researcher, Pragya Gupta is trained in Indian classical music, enjoys baking, inventive craftwork and learning about different cultures. She is currently doing her PhD at the University of Melbourne in Australia, where she is researching new ways to treat brain cancers.

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