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Wednesday February 26, 2025

Congratulations to Prerna Mudai,
2024 ASI Global Outreach Awardee

 



We warmly congratulate
Prerna Mudai
winner of the 2024 ASI Global Outreach Award



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I would like to extend my gratitude and appreciation to the ASI Award Committee for selecting me for the Global Outreach Award.

I am a PhD candidate at the Innate Immunology Lab, School of Chemistry and Molecular Biosciences at the University of Queensland (UQ). I am working on a project on Toll-like receptor 2 signalling mechanisms under the supervision of Prof. Katryn Stacey. I was born in Delhi, India and completed my Bachelors in Science from the University of Delhi in 2018. I moved to Australia to pursue my Masters in Biotechnology at UQ. I completed it in 2021 and my one-year research project during my Masters with Prof. Kate on Inflammasomes motivated me to continue doing a PhD in Innate Immunology. 

Since childhood, I loathed stereotypes, loved solving mysteries and was excruciatingly—to people around me—curious. My dream was to ask enough questions to be able to answer questions, asked by people who I motivated to ask questions. And just like the above sentence, my dream didn’t make sense to many. I found that understanding most concepts of life needed the pursuit of science. My interest in scientific research, though, peaked once I started doing summer and winter research projects during my Bachelors at the University of Delhi. One of these projects was on Antimicrobial Finishing of Textiles using Natural Bioactive Agents, under the guidance of Dr Simran Luthra and Dr Rekha Kumari, where we investigated the extraction of antimicrobial natural dyes from plant sources including turmeric rhizomes and safflower petals, and their colour fixation to different textile materials using various mordants. I moved on to pursue my Masters at UQ where I started my journey into Innate Immunology with a one-month Winter Research Scholarship project. I worked on the Inflammasome Complex under the guidance of Prof. Katryn Stacey which culminated into becoming a one-year research project for my Masters. 

Inflammasomes are multimeric protein complexes which act as a signalling hub in innate immunity. Inflammasomes are activated in response to infections as well as a wide range of cellular and environmental stresses. Their key role in both chronic and acute inflammatory pathologies means there is great interest in research on the regulation and function of the inflammasome complex. The intricacies of the innate immune system intrigued me to continue in the same lab to do a PhD. However, I moved on to focus another important facet of Innate Immunity, proteins called Toll-like receptors (TLRs). My project focuses on characterising the signalling mechanism of TLR 2.  TLRs are proteins that drive activation of the innate immune system by the stimulation of signalling pathways in the cell through recognition of characteristic pathogen molecules and indicators of cell stress/damage. TLR signalling has proved to have an essential implication in the manifestation of a variety of acute and chronic inflammatory pathologies. Conserved in all TLRs are intracellular TIR domains (Toll-interleukin-1 receptor) that act like adaptor molecules to transduce the inflammatory signal upto the nucleus. My project aims to investigate TLR2, that forms heterodimer complexes with TLR1 and TLR6 and activates a complex signalling cascade involving higher-order assembly of several adaptors and downstream effectors like MAL, MyD88, kinases and NFkB; and to elucidate the structure of the TLR2 TIR domain complex by cryo-electron microscopy and validate their role in signalling by cell biology techniques. 

 

Fig: hEKBlue-MD2-CD14- NFκB Zs Green reporter cell .This is a reporter assay I have developed in hEK Blue cells as part of my PhD project to reconstitute TLR2 signalling and study it through a fluorophore-tagged reporter gene. A ZsGreen-tagged NFκB reporter was stably integrated in hEK cells lacking TLR2 but expressing MD2, CD14, TLR1 and TLR6 endogenously. TLR2 mutants tagged with mScarlet-I were transiently transfected in the cells.

Doing a PhD as an immigrant as well as a student is surely not for the faint of the heart. But more than the emotional or mental tribulations, it is financially a hard journey. If not for the different scholarship awards and stipends, getting admitted into a PhD and continuing it would have not been possible for me. Surviving the financial distress of being a student living in the age of high disparity between income and living expenses is a silent struggle. It gets hidden behind the noise of the mental stresses and fears of failed experiments that you can find any PhD student harping about. Amongst all this, affording to go to considerable conferences and travel sounds a far cry even with supportive student funds that get get quickly exhausted. 

Thanks to the ASI Global Outreach Award, I can continue to be a member of ASI, and stay updated about the Immunology scene in Australia. I have also been able to register for and attend the ASI 2024 conference at Sydney because of this award where I met researchers in numerous fields of Immunology and was inspired by the progress being made in understanding the innate immune system and the breakthroughs in alleviating immune diseases. I was also able to communicate my research to the immunology community through the BD Science Communication and Postgraduate Poster Presentation opportunities. I am making great progress in my research, and I am excited about the results of the mutagenesis of TLR2 proteins and how they interact in chimeric forms. I am very grateful to ASI for organising ASI 2024 where I was able to communicate this research and it was only made possible because of the Global Outreach Award. Thank you, ASI.

Publications List

  • Thygesen SJ, Burgener SS, Mudai P, Monteleone M, Boucher D, Sagulenko V, Schroder K, Stacey KJ. Fluorochrome-labeled inhibitors of caspase-1 require membrane permeabilization to efficiently access caspase-1 in macrophages. Eur J Immunol. 2024 May;54(5):e2350515. doi: 10.1002/eji.202350515. Epub 2024 Feb 15. PMID: 38361219.

  • Rahaman MH, Thygesen SJ, Maxwell MJ, Kim H, Mudai P, Nanson JD, Jia X, Vajjhala PR, Hedger A, Vetter I, Haselhorst T, Robertson AAB, Dymock B, Ve T, Mobli M, Stacey KJ, Kobe B. o-Vanillin binds covalently to MAL/TIRAP Lys-210 but independently inhibits TLR2. J Enzyme Inhib Med Chem. 2024 Dec;39(1):2313055. doi: 10.1080/14756366.2024.2313055. Epub 2024 Feb 28. PMID: 38416868; PMCID: PMC10903754.

Author: Prerna Mudai


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