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- A new regulator of 'stemness' to create dendritic cell factories for immunotherapy
- Advanced imaging interrogation of pathogen induced NETosis
- Cancer driver deserts
- Cryo-electron microscopy of Wnt signalling complexes
- Deciphering the heterogeneity of breast cancer at the epigenetic and genetic levels
- Developing drugs to block malaria transmission
- Developing new computational tools for CRISPR genomics to advance cancer research
- Developing novel antibody-based methods for regulating apoptotic cell death
- Discovering novel paradigms to cure viral and bacterial infections
- Discovery and targeting of novel regulators of transcription
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Do membrane forces govern assembly of the deadly apoptotic pore?
- Doublecortin-like kinases, drug targets in cancer and neurological disorders
- E3 ubiquitin ligases in neurodegeneration, autoinflammation and cancer
- Engineering improved CAR-T cell therapies
- Epigenetic biomarkers of tuberculosis infection
- Exploiting cell death pathways in regulatory T cells for cancer immunotherapy
- Finding treatments for chromatin disorders of intellectual disability
- Functional epigenomics in human B cells
- Genomic rearrangement detection with third generation sequencing technology
- How does DNA damage shape disease susceptibility over a lifetime?
- How does DNA hypermutation shape the development of solid tumours?
- How platelets prevent neonatal stroke
- Human lung protective immunity to tuberculosis
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigating the role of dysregulated Tom40 in neurodegeneration
- Investigating the role of mutant p53 in cancer
- Lupus: proteasome inhibitors and inflammation
- Machine learning methods for somatic genome rearrangement detection
- Malaria: going bananas for sex
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- Minimising rheumatic adverse events of checkpoint inhibitor cancer therapy
- Mutational signatures of structural variation
- Naturally acquired immune response to malaria parasites
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- Revealing the epigenetic origins of immune disease
- Reversing antimalarial resistance in human malaria parasites
- Structural and functional analysis of DNA repair complexes
- Targeting human infective coronaviruses using alpaca antibodies
- Towards targeting altered glial biology in high-grade brain cancers
- Uncovering the real impact of persistent malaria infections
- Understanding Plasmodium falciparum invasion of red blood cells
- Understanding how malaria parasites sabotage acquisition of immunity
- Understanding malaria infection dynamics
- Understanding the mechanism of type I cytokine receptor activation
- Unveiling the heterogeneity of small cell lung cancer
- Using alpaca antibodies to understand malaria invasion and transmission
- Using combination immunotherapy to tackle heterogeneous brain tumours
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Joanna Groom-Projects
Researcher:
Chemokine control of T cell host defence and memory
A defining feature of immunity is the acquisition and maintenance of immunological memory, which confers enhanced protection against pathogens.
Exploiting this, vaccine development has saved the lives of millions worldwide. Despite successes, considerable challenges remain for the development of vaccines against a number of recalcitrant viral infections of global importance.
This study investigates the cellular players and interactions that determine fate T cell fate decisions between effector and memory formation and will reveal how cellular positioning influences the maintenance and function of memory responses.
Team members
Brigette Duckworth, Ben Broomfield, Verena Wimmer (Centre for Dynamic Imaging), Kelly Rogers (Centre for Dynamic Imaging), Marc Pellegrini (Infectious Diseases and Immune Defence), Melissa Davis (Bioinformatics), Scott Mueller (University of Melbourne), Adam Wheatley (University of Melbourne)
Project references
Duckworth DC, Lafouresse F, Wimmer VC, Broomfield BJ, Alexandre YO, Sheikh AA, Qin RZ, Alvarado C, Mielke LA, Pellegrini M, Mueller SN, Boudier T, Rogers KL, Groom JR. Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands. Nat Immunol 2021 Apr;22(4):434-448. PMID: 33649580
Duckworth BC, Groom JR. Conversations that count: Cellular interactions that drive T cell fate. Immunol Rev 2021 Mar:300(1):203-219. PMID: 33586207
Kelly HG, Tan HX, Juno JA, Esterbauer R, Ju Y, Jiang W, Wimmer VC, Duckworth BC, Groom JR, Caruso F, Kanekiyo M, Kent SJ, Wheatley AK. Self-assembling influenza nanoparticle vaccines drive extended germinal center activity and memory B cell maturation. JCI Insight 2020 May 21:5(10)e:136653. PMID: 32434990
Marsman C, Lafouresse F, Liao Y, Baldwin TM, Mielke LA, Hu Y, Mack M, Hertzog PJ, de Graaf CA, Shi W, Groom JR. Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation. Immunol Cell Biol. 2018 Nov;96(10):1083-1094. PMID: 29870118.
Groom JR, Richmond J, Murooka TT, Sorensen EW, Sung JH, Bankert K, von Andrian UH, Moon JJ, Mempel TR, Luster AD. CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation. Immunity. 2012 Dec 14;37(6):1091-103. PMID: 23123063.
Multiple paths of TFH differentiation and their impact on B cell protection against infection and antibody-mediated disease
T follicular helper (TFH) cells are a subset of effector CD4+ T cells that promote B cell maturation into high affinity plasma and memory cells. Almost all current vaccines protect via the induction of long-term antibody responses and circulating TFH numbers are reliable biomarkers of vaccination. How diverse pathogen-specific signals direct appropriate protective B cell responses is currently unknown.
This project combines diverse infection models, advanced imaging and transcriptional profiling to provide mechanistic insight into the processes underlying TFH heterogeneity, which is likely to be a key source of flexibility for adaptive immunity.
Further, a key outcome of this project is to identify mechanisms of TFH heterogeneity in order to treat antibody-dependent inflammatory diseases such as severe asthma and lupus.
Team members
Amania Sheikh, Lennard Dalit, in collaboration with Vanessa Bryant, Stephen Nutt (Molecular Immunology), Shalin Naik, Gabrielle Belz, Phil Hansbro (Centenary Institute), Wei Shi (Bioinformatics division), Kelly Rogers (Centre for Dynamic Imaging), Kim Jacobson (Monash University), Colby Zaph (Monash University) and Katherine Kedzierska (University of Melbourne)
Project references
Sheikh AA, Groom JR. Transcription tipping points for T follicular helper cell and T-helper 1 cell fate commitment. Cell Mol Immunol 2021 Mar;18(3):528-538. PMID: 32999454
Kealy L, Di Pietro A, Hailes L, Scheer S, Dalit L, Groom JR, Zaph C, Good-Jacobson KL. The Histone Methyltransferase DOT1L Is Essential for Humoral Immune Responses. Cell Rep 2020 Dec 15;33(11):108504. PMID: 33326791
Sheikh AA, Cooper L, Feng M, Souza-Fonseca-Guimaraes F, Lafouresse F, Duckworth BC, Huntington ND, Moon JJ, Pellegrini M, Nutt SL, Belz GT, Good-Jacobson KL, Groom JR. Context-Dependent Role for T-bet in T Follicular Helper Differentiation and Germinal Center Function following Viral Infection. Cell Rep. 2019 Aug 13;28(7):1758-1772. PMID: 31412245
Piovesan D, Tempany J, Di Pietro A, Baas I, Yiannis C, O'Donnell K, Chen Y, Peperzak V, Belz GT, Mackay CR, Smyth GK, Groom JR, Tarlinton DM, Good-Jacobson KL. c-Myb Regulates the T-Bet-Dependent Differentiation Program in B cells to Coordinate Antibody Responses. Cell Rep. 2017 Apr 18;19(3):461-470. PMID: 28423310
Dissecting the induction and integration of T cell migration cues
Our immune system consists of specialised cells that collaborate to defeat invading pathogens. The integration of migration signals helps balance protective and memory differentiation fates, leading to clearance of infection and cancer and the establishment of immunological memory. How cells navigate these interactions is a dilemma of critical importance to human health globally.
This study uses advanced live imaging platforms to determine how T cells integrate complex migration cues. Further, we investigate the cell-type specific patrolling cues that control migration to inflammatory sites to clear infection and cancer.
Team members
Raymond Qin in collaboration with Kelly Rogers (Centre for Dynamic Imaging), Niall Geoghegan (Centre for Dynamic Imaging)
Project references
Groom JR. Regulators of T-cell fate: Integration of cell migration, differentiation and function. Immunol Rev. 2019 May;289(1):101-114. PMID: 30977199
Targeting T cell interactions to restore balance from inflammation towards immune protection
Following viral infection, immune cells coordinate the induction of inflammatory responses that clear infection and promote protection, while simultaneously balancing the risk of severe immune pathology. The balance between immune protection and pathology has been highlighted in the coronavirus disease 2019 (COVID-19) pandemic.
COVID-19 patients can display a spectrum of symptoms that vary from mild, to severe and fatal immune pathology. How this pathophysiology range impacts the formation of protective, humoral immunity has not been tested.
Using our 3D imaging platforms we have identified new cellular networks that underpin the decision between inflammation or protection during viral infections. We will examine these T cell interactions in the context of different viral infections, including SARS-CoV-2 to identify therapies that reduce severe immune pathology and improve vaccination success.
Team members
Carolina Alvarado, Ben Broomfield (in collaboration with Vanessa Bryant), Stephen Nutt, Marc Pellegrini, Diana Hansen, John Silke, Melissa Davis, Ivo Mueller, and Stephen Kent (University of Melbourne).
Project references
Sheikh AA, Groom JR. Transcription tipping points for T follicular helper cell and T-helper 1 cell fate commitment. Cell Mol Immunol 2021 Mar;18(3):528-538. PMID: 32999454
Sheikh AA, Cooper L, Feng M, Souza-Fonseca-Guimaraes F, Lafouresse F, Duckworth BC, Huntington ND, Moon JJ, Pellegrini M, Nutt SL, Belz GT, Good-Jacobson KL, Groom JR. Context-Dependent Role for T-bet in T Follicular Helper Differentiation and Germinal Center Function following Viral Infection. Cell Rep. 2019 Aug 13;28(7):1758-1772. PMID: 31412245.