Dr Parimala Vajjhala

Research Officer

School of Chemistry and Molecular Biosciences
Faculty of Science
p.vajjhala@uq.edu.au
+61 7 336 54881

Overview

Research Interests

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    My current research focuses on understanding the mechanisms of activation of pattern recognition receptors (PRRs) of the innate immune system and the signalling complexes that they initiate. The innate immune system plays a key role in the initial defence of a host against pathogens as well as in the activation of the adaptive immune system. In addition to being activated by pathogen-associated molecular patterns (PAMPs), some PRRs are activated by endogenous damage-associated molecular patterns (DAMPs), also known as danger-associated molecular patterns. Excessive activation of certain PRRs can lead to inflammation and cell death, which are implicated in the pathology of infectious and non-infectious diseases. Thus, a detailed understanding of the activation of PRRs and the complexes that mediate inflammation and cell death may lead to the development of novel therapies.
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    I have worked on inflammasome complexes that assemble upon activation of cytosolic PRRs including AIM2, which is activated by cytosolic DNA, and NLRP3, which is activated by a wide range of PAMPs and DAMPs. Inflammasomes recruit and activate caspase-1, which cleaves pro-inflammatory cytokines to their active forms that mediate inflammation, as well as caspase-8, which mediates apoptosis. Deregulated inflammasome function is implicated in the pathogenesis of common diseases including atherosclerosis, obesity, diabetes and Alzheimer’s disease, as well as kidney and liver diseases. My work, under the guidance of Assoc. Prof. Katryn Stacey (SCMB, UQ) and Dr. Justine Hill (formerly SCMB, UQ) and also in collaboration with Prof. Hao Wu (Harvard Medical School), has given key insights into the death-fold domain interactions that mediate inflammasome assembly and into the recruitment and activation of caspases. I also contributed to the development of a novel flow cytometry based assay to quantify inflammasome assembly.
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    More recently, I have worked on Toll-like receptor 4 (TLR4) activation. TLR4 is a plasma membrane PRR best known for mediating an inflammatory response to the lipopolysaccharide (LPS) of the outer membrane of Gram-negative bacteria. Although TLR4 activation induces release of proinflammatory cytokines that can be protective, dysregulated TLR4 responses can lead to life-threatening systemic inflammation. TLR4 is also activated by endogenous molecules and promotes the pathology of non-infectious diseases including atherosclerosis, obesity, diabetes, Alzheimer’s disease, rheumatoid arthritis, epilepsy and ischemia/reperfusion injury. Upon activation, the intracellular TIR domain of TLR4 recruits adaptor proteins with TIR domains including MAL and MyD88. The complexes formed initiate downstream signalling pathways. In a project, which is a collaboration with Prof. Bostjan Kobe (SCMB, UQ), Dr. Thomas Ve (Griffith University) and Assoc. Prof. Katryn Stacey (SCMB, UQ), the interaction interfaces of MAL TIR and MyD88 TIR were defined. These studies have given key insights into assembly of TLR4 signalling complexes.

Qualifications

  • Bachelor of Science, The University of Queensland
  • Doctor of Philosophy, The University of Queensland
  • Bachelor of Science (Honours), The University of Queensland

Publications

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Supervision

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Publications

Book Chapter

  • Sester, David P., Zamoshnikova, Alina, Thygesen, Sara J., Vajjhala, Parimala R., Cridland, Simon O., Schroder, Kate and Stacey, Katryn J. (2016). Assessment of inflammasome formation by flow cytometry. In Coligan, John E., Bierer, Barbara, Margulies, David H., Shevach, Ethan M. and Strober, Warren (Ed.), Current protocols in immunology (pp. 14.40.1-14.40.29) Hoboken, NJ United States: John Wiley & Sons. doi:10.1002/cpim.13

Journal Article

Conference Publication

  • Vajjhala, P., Lu, A., Brown, D., Sagulenko, V, Schroder, K., Stow, J., Wu, H. and Stacey, K. (2016). Molecular arrangement and activation of procaspases-1 and-8 at inflammasomes. In: European Journal of Immunology. ICI 2016 International Congress of Immunology, Melbourne, Australia, (1031-1031). 21-26 August 2016.

Other Outputs

PhD and MPhil Supervision

Current Supervision

Completed Supervision