Dr Parimala Vajjhala
Dr

Parimala Vajjhala

Email: 
Phone: 
+61 7 336 54881

Availability

Dr Parimala Vajjhala is:
Available for supervision

Fields of research

Biological Sciences Microbiology

Qualifications

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

Research interests

  • .

    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.

  • .

    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.

  • .

    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.

Search Professor Parimala Vajjhala’s works on UQ eSpace

27 works between 2001 and 2024
All (27) Journal Article (23) Book Chapter (1) Conference Publication (2) Other Outputs (1)

1 - 20 of 27 works

2024

Journal Article

o-Vanillin binds covalently to MAL/TIRAP Lys-210 but independently inhibits TLR2

Rahaman, Md. Habibur, Thygesen, Sara J., Maxwell, Michael J., Kim, Hyoyoung, Mudai, Prerna, Nanson, Jeffrey D., Jia, Xinying, Vajjhala, Parimala R., Hedger, Andrew, Vetter, Irina, Haselhorst, Thomas, Robertson, Avril A. B., Dymock, Brian, Ve, Thomas, Mobli, Mehdi, Stacey, Katryn J. and Kobe, Bostjan (2024). o-Vanillin binds covalently to MAL/TIRAP Lys-210 but independently inhibits TLR2. Journal of Enzyme Inhibition and Medicinal Chemistry, 39 (1) 2313055, 2313055. doi: 10.1080/14756366.2024.2313055

o-Vanillin binds covalently to MAL/TIRAP Lys-210 but independently inhibits TLR2

2023

Journal Article

Kinetics of severe dengue virus infection and development of gut pathology in mice

Pliego Zamora, Adriana, Kim, Jaehyeon, Vajjhala, Parimala R., Thygesen, Sara J., Watterson, Daniel, Modhiran, Naphak, Bielefeldt-Ohmann, Helle and Stacey, Katryn J. (2023). Kinetics of severe dengue virus infection and development of gut pathology in mice. Journal of Virology, 97 (11) ARTN e0125123, e0125123. doi: 10.1128/jvi.01251-23

Kinetics of severe dengue virus infection and development of gut pathology in mice

2023

Journal Article

TLR4 phosphorylation at tyrosine 672 activates the ERK/c‐FOS signaling module for LPS‐induced cytokine responses in macrophages

Curson, James E. B., Liu, Liping, Luo, Lin, Muusse, Timothy W., Lucas, Richard M., Gunther, Kimberley S., Vajjhala, Parimala R., Abrol, Rishika, Jones, Alun, Kapetanovic, Ronan, Stacey, Katryn J., Stow, Jennifer L. and Sweet, Matthew J. (2023). TLR4 phosphorylation at tyrosine 672 activates the ERK/c‐FOS signaling module for LPS‐induced cytokine responses in macrophages. European Journal of Immunology, 53 (7) e2250056, e2250056. doi: 10.1002/eji.202250056

TLR4 phosphorylation at tyrosine 672 activates the ERK/c‐FOS signaling module for LPS‐induced cytokine responses in macrophages

2022

Journal Article

Flow cytometric reporter assays provide robust functional analysis of signaling complexes

Muusse, Timothy W., Lee, Morris Y.L., Kim, Hyoyoung, Parat, Marie-Odile, Nanson, Jeffrey D., Kobe, Bostjan, Vajjhala, Parimala R. and Stacey, Katryn J. (2022). Flow cytometric reporter assays provide robust functional analysis of signaling complexes. Journal of Biological Chemistry, 298 (12) 102666, 102666. doi: 10.1016/j.jbc.2022.102666

Flow cytometric reporter assays provide robust functional analysis of signaling complexes

2021

Journal Article

MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography

Clabbers, Max T. B., Holmes, Susannah, Muusse, Timothy W., Vajjhala, Parimala R., Thygesen, Sara J., Malde, Alpeshkumar K., Hunter, Dominic J. B., Croll, Tristan I., Flueckiger, Leonie, Nanson, Jeffrey D., Rahaman, Md. Habibur, Aquila, Andrew, Hunter, Mark S., Liang, Mengning, Yoon, Chun Hong, Zhao, Jingjing, Zatsepin, Nadia A., Abbey, Brian, Sierecki, Emma, Gambin, Yann, Stacey, Katryn J., Darmanin, Connie, Kobe, Bostjan, Xu, Hongyi and Ve, Thomas (2021). MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography. Nature Communications, 12 (1) 2578, 1-14. doi: 10.1038/s41467-021-22590-6

MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography

2017

Journal Article

Caspase-1 is an apical caspase leading to caspase-3 cleavage in the AIM2 inflammasome response, independent of caspase-8

Sagulenko, Vitaliya, Vitak, Nazarii, Vajjhala, Parimala, Vince, James E and Stacey, Katryn J (2017). Caspase-1 is an apical caspase leading to caspase-3 cleavage in the AIM2 inflammasome response, independent of caspase-8. Journal of Molecular Biology, 430 (2), 238-247. doi: 10.1016/j.jmb.2017.10.028

Caspase-1 is an apical caspase leading to caspase-3 cleavage in the AIM2 inflammasome response, independent of caspase-8

2017

Journal Article

Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling

Ve, Thomas, Vajjhala, Parimala, Hedger, Andrew, Croll, Tristan, DiMaio, Frank, Horsefield, Shane, Yu, Xiong, Lavrencic, Peter, Hassan, Zahid, Morgan, Garry P., Mansell, Ashley, Mobli, Mehdi, O'Carroll, Ailis, Chauvin, Brieuc, Gambin, Yann, Sierecki, Emma, Landsberg, Michael J., Stacey, Katryn, Egelman, Edward H. and Kobe, Bostjan (2017). Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling. Nature Structural and Molecular Biology, 24 (9), 743-751. doi: 10.1038/nsmb.3444

Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling

2017

Journal Article

The molecular mechanisms of signaling by cooperative assembly formation in innate immunity pathways

Vajjhala, Parimala R., Ve, Thomas, Bentham, Adam, Stacey, Katryn J. and Kobe, Bostjan (2017). The molecular mechanisms of signaling by cooperative assembly formation in innate immunity pathways. Molecular Immunology, 86, 23-37. doi: 10.1016/j.molimm.2017.02.012

The molecular mechanisms of signaling by cooperative assembly formation in innate immunity pathways

2016

Journal Article

Cryo-EM structure of caspase-8 tandem DED filament reveals assembly and regulation mechanisms of the death-inducing signaling complex

Fu, Tian-Min, Li, Yang, Lu, Alvin, Li, Zongli, Vajjhala, Parimala R., Cruz, Anthony C., Srivastava, Devendra B., DiMaio, Frank, Penczek, Pawel A., Siegel, Richard M., Stacey, Katryn J., Egelman, Edward H. and Wu, Hao (2016). Cryo-EM structure of caspase-8 tandem DED filament reveals assembly and regulation mechanisms of the death-inducing signaling complex. Molecular Cell, 64 (2), 236-250. doi: 10.1016/j.molcel.2016.09.009

Cryo-EM structure of caspase-8 tandem DED filament reveals assembly and regulation mechanisms of the death-inducing signaling complex

2016

Conference Publication

Cytosolic DNA, HIN-200 proteins and inflammasome activation

Stacey, K. J., Vajjhala, P. R., Sagulenko, V, Thygesen, S., Vitak, N. and Sester, D. P. (2016). Cytosolic DNA, HIN-200 proteins and inflammasome activation. International Congress of Immunology (ICI), Melbourne, VIC Australia, 21-26 August 2016. Weinheim, Germany: Wiley.

Cytosolic DNA, HIN-200 proteins and inflammasome activation

2016

Conference Publication

Molecular arrangement and activation of procaspases-1 and-8 at inflammasomes

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. ICI 2016 International Congress of Immunology, Melbourne, Australia, 21-26 August 2016. Weinheim, Germany: Wiley.

Molecular arrangement and activation of procaspases-1 and-8 at inflammasomes

2016

Book Chapter

Assessment of inflammasome formation by flow cytometry

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. Current protocols in immunology. (pp. 14.40.1-14.40.29) edited by Coligan, John E., Bierer, Barbara, Margulies, David H., Shevach, Ethan M. and Strober, Warren. Hoboken, NJ United States: John Wiley & Sons. doi: 10.1002/cpim.13

Assessment of inflammasome formation by flow cytometry

2015

Journal Article

The inflammasome adaptor ASC induces procaspase-8 death effector domain filaments

Vajjhala, Parimala R., Lu, Alvin, Brown, Darren L., Pang, Siew Wai, Sagulenko, Vitaliya, Sester, David P., Cridland, Simon O., Hill, Justine M., Schroder, Kate, Stow, Jennifer L., Wu, Hao and Stacey, Katryn J. (2015). The inflammasome adaptor ASC induces procaspase-8 death effector domain filaments. Journal of Biological Chemistry, 290 (49), 29217-29230. doi: 10.1074/jbc.M115.687731

The inflammasome adaptor ASC induces procaspase-8 death effector domain filaments

2015

Journal Article

A novel flow cytometric method to assess inflammasome formation

Sester, David P., Thygesen, Sara J., Sagulenko, Vitaliya, Vajjhala, Parimala R., Cridland, Jasmyn A., Vitak, Nazarii, Chen, Kaiwen W., Osborne, Geoffrey W., Schroder, Kate and Katryn J. Stacey (2015). A novel flow cytometric method to assess inflammasome formation. The Journal of Immunology, 194 (1), 455-462. doi: 10.4049/jimmunol.1401110

A novel flow cytometric method to assess inflammasome formation

2014

Journal Article

Identification of multifaceted binding modes for pyrin and ASC pyrin domains gives insights into pyrin inflammasome assembly

Vajjhala, Parimala R., Kaiser, Sebastian, Smith, Sarah J., Ong, Qi-Rui, Soh, Stephanie L., Stacey, Katryn J. and Hill, Justine M. (2014). Identification of multifaceted binding modes for pyrin and ASC pyrin domains gives insights into pyrin inflammasome assembly. Journal of Biological Chemistry, 289 (34), 23504-23519. doi: 10.1074/jbc.M114.553305

Identification of multifaceted binding modes for pyrin and ASC pyrin domains gives insights into pyrin inflammasome assembly

2013

Journal Article

AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC

Sagulenko, V., Thygesen, S. J., Sester, D. P., Idris, A., Cridland, J. A., Vajjhala, P. R., Roberts, T., Schroder, K., Vince, J. E., Hill, J. M., Silke, J. and Stacey, K. J. (2013). AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC. Cell Death and Differentiation, 20 (9), 1149-1160. doi: 10.1038/cdd.2013.37

AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC

2013

Journal Article

The structure of the caspase recruitment domain of BinCARD reveals that all three cysteines can be oxidized

Chen, Kai-En, Richards, Ayanthi A., Caradoc-Davies, Tom T., Vajjhala, Parimala R., Robin, Gautier, Lua, Linda H. L., Hill, Justine M., Schroder, Kate, Sweet, Matthew J., Kellie, Stuart, Kobe, Bostjan and Martin, Jennifer (2013). The structure of the caspase recruitment domain of BinCARD reveals that all three cysteines can be oxidized. Acta Crystallographica Section D: Biological Crystallography, 69 (5), 774-784. doi: 10.1107/S0907444913001558

The structure of the caspase recruitment domain of BinCARD reveals that all three cysteines can be oxidized

2012

Journal Article

Multiple Binding Sites on the Pyrin Domain of ASC Protein Allow Self-association and Interaction with NLRP3 Protein

Vajjhala, Parimala R., Mirams, Ruth E. and Hill, Justine M. (2012). Multiple Binding Sites on the Pyrin Domain of ASC Protein Allow Self-association and Interaction with NLRP3 Protein. Journal of Biological Chemistry, 287 (50), 41732-41743. doi: 10.1074/jbc.M112.381228

Multiple Binding Sites on the Pyrin Domain of ASC Protein Allow Self-association and Interaction with NLRP3 Protein

2009

Journal Article

Three-dimensional structure of AAA ATPase Vps4: Advancing structural insights into the mechanisms of endosomal sorting and enveloped virus budding

Landsberg, Michael J., Vajjhala, Parimala Rao, Rothnagel, Rosalba, Munn, Alan Leslie and Hankamer, Ben (2009). Three-dimensional structure of AAA ATPase Vps4: Advancing structural insights into the mechanisms of endosomal sorting and enveloped virus budding. Structure, 17 (3), 427-437. doi: 10.1016/j.str.2008.12.020

Three-dimensional structure of AAA ATPase Vps4: Advancing structural insights into the mechanisms of endosomal sorting and enveloped virus budding

2008

Journal Article

The Vps4 C-terminal helix is a critical determinant for assembly and ATPase activity and has elements conserved in other members of the meiotic clade of AAA ATPases.

Vajjhala, P. R., Nguyen , C. H., Landsberg, M. J., Kistler, C., Gan, A. L., King, G. F., Hankamer, B. and Munn, A. L. (2008). The Vps4 C-terminal helix is a critical determinant for assembly and ATPase activity and has elements conserved in other members of the meiotic clade of AAA ATPases.. Febs Journal, 275 (7), 1427-1449. doi: 10.1111/j.1742-4658.2008.06300.x

The Vps4 C-terminal helix is a critical determinant for assembly and ATPase activity and has elements conserved in other members of the meiotic clade of AAA ATPases.

Current funding

  • 2021 - 2025
    Mammalian endotoxin: Characterisation of highly inflammatory endogenous material
    NHMRC IDEAS Grants
    Open grant

Availability

Dr Parimala Vajjhala is:
Available for supervision

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Supervision history

Current supervision

Completed supervision

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