Gray-Projects

Gray-Projects

Researcher: 

Projects

Molecular Control of Thymic Function

T cells are made in the thymus. Their differentiation and tolerance of the body’s tissues is directed by signals from epithelial cells. We aim to elucidate the signalling networks and apoptotic processes that form and maintain the epithelium of the thymus. Leveraging this knowledge to understand how defects in these pathways contribute to autoimmune disease and immunodeficiency is a key focus of this program, with a view to correcting these problems via cell therapies or targeted small molecules.

Team members: Dr Julie Sheridan, Dr Reema Jain, Ms Melanie Heinlein

Microscopic image of the thymus
'Thymus Wreath' by Melanie Heinlein, 2016

 

Integration of Immunological Tolerance Mechanisms

Our studies of defects in apoptosis in laboratory models revealed that when deletion is impaired, other tolerance mechanisms are amplified. The relative importance of T cell regulation and anergy can be explored in these models towards a better understanding of how the barriers to autoimmunity interact.

Team member: Ms Antonia Policheni

Molecular Control of FOXP3+ Regulatory T Cell Homeostasis

FOXP3+ Regulatory T (Treg) cells dampen immune responses and are critical for the maintenance of immune tolerance.

In this project we seek to understand the molecular control of Treg cell survival, with a view to finding unique properties that could be therapeutically targeted to modulate their potent immune function in disease. 

Project resources

  • Teh CE, Lalaoui N, Jain R, Policheni AN, Heinlein M, Alvarez-Diaz S, Sheridan JM, Rieser E, Deuser S, Darding M, Koay HF, Hu Y, Kupresanin F, O'Reilly LA, Godfrey DI, Smyth GK, Bouillet P, Strasser A, Walczak H, Silke J, Gray DH. Linear Ubiquitin Chain Assembly Complex  Coordinates Late Thymic T Cell Differentiation and Regulatory T Cell Homeostasis Nat. Comm. 2016 Nov 18;7:13353. doi: 10.1038/ncomms13353 PMID: 27857075 
  • Pierson, Cauwe, Policheni, Schlenner, Franckaert, Berges, Humblet-Baron, Schonefeldt, Herold, Hildeman, Strasser, Bouillet, Lu, Matthys, Freitas, Luther, Weaver, Dooley, Gray DH*, Liston A* . Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3+ regulatory T cells. Nat. Immunol. 2013 Sep;14(9):959-65. PMID: 23852275
  • Liston A, Gray DH. Homeostatic control of regulatory T cell diversity. Nat. Rev. Immunol. 2014 Mar 14(3):154-65 PMID: 24481337

* joint last authors

Team member: Dr Charis Teh