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

细胞毒性T淋巴细胞（ctl）是一种特殊类型的白细胞，在对抗病毒感染和癌症中发挥重要作用。事实上，一些新的癌症治疗方法专注于提高这些细胞对抗肿瘤的反应。像体内的许多细胞一样，ctl对周围环境非常敏感，它们会根据周围的其他细胞和信号分子改变自己的反应。因此，开发改变这些细胞功能的药物是很困难的。这种药物开发过程的第一步是了解这些细胞在不同环境下的行为。对免疫反应有利，但对研究人员来说令人困惑的是，CTL反应的内部信号事件非常迅速，大约几分钟。因此，在一组ctl中，每个细胞在其反应中可能处于略有不同的阶段，并表现出不同的特征。直到最近，用于检测这些细胞变化的技术需要将数千个细胞聚集在一起。因此，测量结果是整个细胞池的平均值，并不能反映每个细胞的精确反应阶段。现在，新技术可以在单个细胞中进行测量，从而可以收集到大量关于单个细胞行为和它们的反应微调步骤的信息。在这个项目中，我们建议在与癌症反应相关的各种情况下检查单个ctl，包括初始激活和免疫增强药物的存在。我们特别感兴趣的是突出潜在的药物靶点和改进分析这种新型数据的方法。

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.