Stephen Nutt-Projects

Stephen Nutt-Projects

Projects

The generation of antibody-secreting plasma cells

Upon activation, mature B cells undergo immunoglobulin class switch recombination and differentiate into antibody-secreting plasma cells, the endpoint of the B cell lineage. The mutually exclusive transcriptomes of B cells and plasma cells are maintained by the antagonistic interplay of two groups of transcription factors, those that maintain the B cell program, including Pax5, Irf8 and Bcl6, and those that promote plasma cell differentiation, notably Irf4 and Blimp1. This project aims to understand how this gene regulatory network is controlled during an immune response and the perturbations that lead to excess plasma cell production and multiple myeloma.

Team members: Simon Willis and Julie Tellier

 

Control of dendritic cell development

Dendritic cells (DCs) form the front line defence against invading pathogens. They are located throughout the body and form an interface between the external environment and the adaptive immune system. To provide this protection, different subsets of DCs have evolved that are specialized to exist in distinct locations and perform unique functions. The DC network is programmed by a group of transcription factors that control the differentiation of the different subsets of DC. In this project we are utilizing genomic technologies with an aim to understand how the transcription factors PU.1 and Irf8 function together to control DC subset diversity and myelopoiesis more generally.

Team members: Michael Chopin, Aleksandar Dakic and Angela D’Amico

 

Regulatory T cell biology

Regulatory T cells (Tregs) are essential for the maintenance of immune homeostasis and the suppression of autoimmune disease. While Foxp3 is continually required to reinforce the Treg program, Tregs can also undergo stimulus-specific differentiation that is regulated by transcription factors typically associated with the differentiation of conventional CD4+ T cells. This results in effector Tregs with unique migratory and functional properties matched to the stimulus that elicited the initial response. In this project we aim to understand both the gene regulatory network responsible for effector Treg differentiation and the functional importance of this process in controlling autoimmune and anti-cancer immunity.

Team members: Erika Cretney, Sheila Dias and Patrick Leung