Gabrielle Belz-Projects

Gabrielle Belz-Projects

Projects

Identification of mechanisms of mucosal protection by innate lymphoid cells during infection

The body’s surface provides a critical barrier shielding us from various mechanical and pathogenic insults by virtue of the physical protection it provides and the presence of specialised populations of innate lymphoid cells (ILCs) that sense inflammatory signals induced by pathogens. This response plays a central role in the development and activation of early immune responses. While ILCs depend on common γ-chain cytokine signaling for their development, an essential component of the armory of these cells is their capacity to produce defensive cytokines when activated by pathogens and tumours. Our focus is to understand the circuitry regulating the development and function of ILC necessary for protective immunity.

Team members: Lucie Rankin, Lisa Mielke, Cyril Seillet in collaboration with Dr Nick Huntington, Dr Sebastian Carotta and Professor Stephen Nutt

Deciphering the function of Id and E-proteins in lymphocyte development and disease

The development and diversification of white blood cells is critical for immune protection against viruses, parasites, bacteria and malignancy. The differential expression of transcription factors and inhibitors of their DNA (Id) binding dictate the development of multiple blood cell lineages. The E-protein family of transcription factors are required for B and T cell development, whereas expression of Id2, which blocks their DNA binding, is essential for innate lymphoid cell (ILC) development. We are combining multiple approaches including mass spectrometry and a unique antibody panel for the different E and Id proteins to identify the interactions that occur between E and Id proteins and other novel transcription factors required to control immune cell development and function.

Team members: Matt Firth in collaboration with Dr Nick Huntington and Associate Professor Lynn Corcoran

 

Deciphering the transcriptional and epigenetic regulation of effector and memory T cell differentiation

A major goal is to understand the mechanisms of T cell memory generation that provide protective immunity. We have developed and use a number of in vivo models including influenza, herpesvirus, LCMV and tuberculosis. These models provide us with an unprecedented opportunity to examine the mechanisms that these pathogens employ to infect hosts and elicit immune protection or to subvert the host responses. Using a variety of approaches including multiparameter flow cytometry, systems biology and global gene expression profiling we aim to define cellular and transcriptional pathways in normal memory T cell differentiation and immune failure.

Team members: Lisa Mielke, Matt Firth in collaboration with Dr Frederick Masson, Assoc Prof Lynn Corcoran, Dr Rhys Allan and Dr Marc Pellegrini

Unravelling the transcriptional regulation of dendritic cell development and function

Specialised subsets of dendritic cells (DCs) provide a crucial link between the innate and adaptive immune responses. The genetic programme that coordinates these distinct DC subsets is controlled by both cytokines and transcription factors. The initial steps in DC specification occur in the bone marrow and result in the generation of precursors committed to either the plasmacytoid or conventional DC pathways. Understanding how DCs undergo further differentiation and lineage diversification in peripheral organs in response to local environmental cues is of key interest and will help us understand how protective immunity develops and how DCs might be targeted in vaccine development.

Team members: Dr Cyril Seillet in collaboration with Dr Michael Chopin and Professor Stephen Nutt