How TNF signalling pathways govern T cell development and homeostasis

How TNF signalling pathways govern T cell development and homeostasis

Project details

T cells integrate information from various TNF receptors to guide their differentiation, life and death. The goal of this project is to elucidate the molecular mechanisms that translate these signals into immune outcomes, with a view to developing novel therapeutic targets for autoimmune disorders.

Our preliminary data have revealed that critical post-translational events downstream of TNF signalling, such as linear ubiquitylation and caspase activation, differentially impact the development and survival of T cell subpopulations. 

This project will build on these discoveries to define how the context of these signals determines immune responses (e.g. T cell subsets involved, inflammatory milieu, pharmacological interventions). Experiments will employ new genetic models, infection challenges, CRISPR/Cas9 genome editing and CyTOF mass cytometry to address these questions.

About our research group

The Gray laboratory works at the interface of the fields of immunology and cell death. We seek to define the cellular and molecular basis of T cell differentiation and death to elucidate pathological mechanisms in immunodeficiency, autoimmunity and cancer. We have projects on: 

  • Foxp3+ regulatory T cell homeostasis (Liston and Gray, Nat.Rev.Immunol., 2014 Mar 14(3):154-65; Pierson et al., Nat.Immunol., 2013 14(9):959-65)
  • Thymus function (Danso-Abeam, et al. Eur.J.Immunol., 2013 43(1):75-84)
  • Immunological tolerance (Gray et al., Immunity, 2012 37(3):451-62; Gray et al., Proc.Natl.Acad.Sci. (USA), 2007 104(46):18193-8)
  • T cell differentiation (Mingueneau, et al., Nat.Immunol., 2013 14(6):619-32)

The lab is composed of two postdoctoral fellows and three PhD students and takes a highly collaborative approach to solving complex problems. We work closely with many groups at the Institute, including the Strasser lab.

 

Microscopy image
Confocal microscopy of a thymus section stained to show the inner medulla, which produces TNF ligands that influence T cell development

 

Researchers:

Dr Daniel Gray

Dr Daniel Gray
Dr
Daniel
Gray
Laboratory Head

Professor Andreas Strasser

Andreas Strasser
Professor
Andreas
Strasser
Joint Division Head

Project Type: