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- A multi-pronged approach to targeting myeloproliferative neoplasms
- A new paradigm of machine learning-based structural variant detection
- A whole lot of junk or a treasure trove of discovery?
- Advanced imaging interrogation of pathogen induced NETosis
- Analysing the metabolic interactions in brain cancer
- Atopic dermatitis causes and treatments
- Boosting the efficacy of immunotherapy in lung cancer
- Building a cell history recorder using synthetic biology for longitudinal patient monitoring
- Characterisation of malaria parasite proteins exported into infected liver cells
- Deciphering the heterogeneity of the tissue microenvironment by multiplexed 3D imaging
- Defining the mechanisms of thymic involution and regeneration
- Delineating the molecular and cellular origins of liver cancer to identify therapeutic targets
- Developing computational methods for spatial transcriptomics data
- Developing drugs to block malaria transmission
- Developing models for prevention of hereditary ovarian cancer
- Developing statistical frameworks for analysing next generation sequencing data
- Development and mechanism of action of novel antimalarials
- Development of novel RNA sequencing protocols for gene expression analysis
- Discoveries in red blood cell production and function
- Discovering epigenetic silencing mechanisms in female stem cells
- Discovery and targeting of novel regulators of transcription
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Dissecting mechanisms of cytokine signalling
- Doublecortin-like kinases, drug targets in cancer and neurological disorders
- Epigenetic biomarkers of tuberculosis infection
- Epigenetics – genome wide multiplexed single-cell CUT&Tag assay development
- Exploiting cell death pathways in regulatory T cells for cancer immunotherapy
- Exploiting the cell death pathway to fight Schistosomiasis
- Finding treatments for chromatin disorders of intellectual disability
- Functional epigenomics in human B cells
- How do nutrition interventions and interruption of malaria infection influence development of immunity in sub-Saharan African children?
- Human lung protective immunity to tuberculosis
- Improving therapy in glioblastoma multiforme by activating complimentary programmed cell death pathways
- Innovating novel diagnostic tools for infectious disease control
- Integrative analysis of single cell RNAseq and ATAC-seq data
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigation of a novel cell death protein
- Malaria: going bananas for sex
- Mapping spatial variation in gene and transcript expression across tissues
- Mechanisms of Wnt secretion and transport
- Multi-modal computational investigation of single-cell communication in metastatic cancer
- Nanoparticle delivery of antibody mRNA into cells to treat liver diseases
- Naturally acquired immune response to malaria parasites
- Organoid-based discovery of new drug combinations for bowel cancer
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- Removal of tissue contaminations from RNA-seq data
- Reversing antimalarial resistance in human malaria parasites
- Role of glycosylation in malaria parasite infection of liver cells, red blood cells and mosquitoes
- Screening for novel genetic causes of primary immunodeficiency
- Single-cell ATAC CRISPR screening – Illuminate chromatin accessibility changes in genome wide CRISPR screens
- Spatial single-cell CRISPR screening – All in one screen: Where? Who? What?
- Statistical analysis of single-cell multi-omics data
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- Using combination immunotherapy to tackle heterogeneous brain tumours
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- Using structural biology to understand programmed cell death
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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.