Understanding the regulation of cytotoxic T lymphocyte signalling and activity through single-cell genomics

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Cytotoxic T lymphocytes (CTLs) are a specialized type of white blood cell that play an important role in combating viral infections and cancer. In fact, several new cancer treatments focus on improving the response of these cells to fight tumours. Like many cells in the body, CTLs are very sensitive to their surroundings, altering their responses based on the other cells and signalling molecules around them. Thus, development of drugs that alter the function of these cells can be difficult. The first step in such a drug development process is understanding how these cells behave in different contexts. Beneficially for immune responses, but confusingly for researchers, the internal signalling events of CTL responses are extremely rapid, on the order of minutes. Thus, within a group of CTLs, each cell may be at a slightly different stage in its response and exhibit different characteristics. Until recently, technologies used to examine changes in these cells required that thousands be pooled together. The measurement was therefore an average across the whole pool of cells and didn't reflect the precise response stage of each individual cell. New technologies now enable measurements to be made in single cells, allowing a huge amount of information to be gathered about how individual cells behave and about the fine-tuned steps of their responses. In this project, we propose to examine single CTLs in various contexts relevant to their responses to cancer, including initial activation and in the presence of immune-enhancing drugs. We are particularly interested in highlighting potential drug targets and in improving methods to analyse this new type of data.