Joanna Groom-Projects

Joanna Groom-Projects

Researcher: 
Dr Joanna Groom

Projects

Last modified: 
Fri, 13/03/2020 - 11:40am

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 (Infection and Immunity division), Melissa Davis (Bioinformatics division), Scott Mueller (University of Melbourne) and Adam Wheatley (University of Melbourne).

Project references 
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.

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. Regulators of T-cell fate: Integration of cell migration, differentiation and function. Immunol Rev. 2019 May;289(1):101-114. PMID: 30977199.

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 (Immunology division), Stephen Nutt (Molecular Immunology), Gabrielle Belz (Immunology division), Phil Hansbro (Centenary Institute), Wei Shi (Bioinformatics division), Kelly Rogers (Centre for Dynamic Imaging), Kim Jacobson (Monash University), Colby Zaph and Katherine Kedzierska (University of Melbourne)

Project references

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

Good-Jacobson KL, Groom JR. Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators that Drive the Creation and Collusion of Autoreactive Lymphcytes. Front Immunol. 2018 Mar 8;9:482. PMID: 29568300

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, Carolina Alvarado, in collaboration with Kelly Rogers (Centre for Dynamic Imaging), Niall Geoghegan (Centre for Dynamic Imaging), Tracy Putoczki, Gabrielle Belz, Marc Pellegrini. 

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.