Omer Dushek

Systems biology of cellular signalling in the immune system

Our laboratory is studying immune cell activation with a particular focus on T cells.

T cells (red) interacting with antigen presenting cells (green)

Schematic of signalling proximal to the T cell antigen receptor

T cells are important white blood cells that continually circulate in the body in search of the molecular signatures ('antigens') of infection and cancer. When encountering such antigens T cells become activated and subsequently initiate immune responses in order to clear these threats. Their inappropriate activation towards innocuous and endogenous antigens leads to allergic and autoimmune responses. A key aim of the laboratory is to understand the 'calculation' that T cells make in deciding to respond to abnormal cells whilst ignoring healthy cells.

The calculation that T cells make is performed by their complex cellular signaling machinery. Given their importance, it is no surprise that many of the signaling proteins that mediate this decision have been identified. Like in other areas of molecular biology, what has emerged is a complex reaction network. The challenge that we now face is no longer to identify new signaling proteins but to understand the interaction among the already identified proteins. Our work aims to directly tackle this challenge using mathematical and experimental tools.

Relevant Publications

Lever M, Lim HS, Kruger P, Nguyen J, Trendel N, Abu-Shah, Maini PK, van der Merwe PA, Dushek O.

Proc Natl Acad Sci USA.

Mukhopadhyay H, de Wet B, Clemens L, Maini PK, Allard J, van der Merwe PA, Dushek O.

Biophys J. 110(8): 1896-906.

Dushek O, van der Merwe PA

Trends in Immunology 35: 153-8.

Lever M, Maini PK, van der Merwe PA, Dushek O

Nature Reviews Immunology 14: 619-29.

Mukhopadhyay H, Cordoba SP, Maini PK, van der Merwe PA, Dushek O

PLOS Computational Biology 9: e1003004.

Dushek O, Aleksic M, Wheeler RJ, Zhang H, Cordoba SP, Peng YC, Chen JL, Cerundolo V, Dong T, Coombs D, van der Merwe PA

Science Signaling 4: ra39.

Aleksic M, Dushek O, Zhang H, Shenderov E, Chen JL, Cerundolo V, Coombs D, van der Merwe PA

Immunity 32: 163-74.

Research Areas