Project details

Lymphocyte regulation is central to all adaptive immune responses. The ability of lymphocytes to be controlled by multiple signals including antigen and costimulatory receptors is well understood at a conceptual and theoretical level. 

We now face the challenge of translating our theories to fit with molecular information and create a multiscale understanding of signal integration and changes in cell fate. A critical element in regulation is control of cell survival. We know that cells are constantly translating their perception of outside signals into changes in their survival program. 

We recently identified a simple threshold-based timer for control of death by B cells. In this project we will explore the regulation of survival in T cells by cytokine and TCR delivered signals. We will monitor expression changes in pro and anti-apoptotic molecules using high-dimensional flow cytometry and vary signals with ligands, such as cytokines (IL-2 and IL-7) and TCR of different affinities and strengths. 

The project will require wet lab skills in tissue culture, flow cytometry and biochemistry, along with dry lab training in data analysis and some mathematical modelling. 

Background work includes: Heinzel, et al Nat Immunol.2017;18:96; Teh, et al Cell Death Differ. 2020 27(7). 

About our research group

This project is a collaboration between two labs. The Hodgkin lab studies the immune system with the goal of building conceptual computational models that can be used to improve vaccine development and treatments for autoimmunity and cancer. 

The Gray lab is expert in the molecular control of cell death in the immune response and cancer, and in the use of high-dimensional methods of analysis.

Experimental work to inform this effort focuses on the control of immune cell fates such as death, division and differentiation. Typical experiments in the lab use cellular division tracking techniques and flow cytometry to measure the effect of changing conditions such as cytokines, altered genetic makeup, or the impact of pharmacological agents on individual cells and how they vary in a population. Single cell and bulk RNA sequencing is used to follow molecular changes corresponding with cell fates. In the lab, experiment-skilled and computer-skilled researchers work together to extract the maximum value from such data.