Innate-immune drivers of cell fate during genotoxic stress

在癌症治疗引起的基因毒性应激反应中，细胞凋亡在细胞命运谱中占据主导地位。因此，许多药物和基因筛选主要识别凋亡驱动因素。然而，细胞凋亡可能不是最有益的命运，因为它是免疫抑制，促进增殖。在这里，我们将开发多种类型的细胞死亡，衰老和炎症的报告。利用这些，我们将进行CRISPR-Cas9筛选，以识别调节这些细胞命运的基因。然后，候选人将使用最先进的显微镜、细胞生物学和质谱技术进行表征。最后，我们将描述可用于靶向治疗的细胞命运反应机制。

In response to the genotoxic stress elicited by cancer therapy, apoptosis dominates the cell fate spectrum. Therefore, many drug- and genetic screens primarily identify apoptotic drivers. However, apoptosis may not be the most beneficial fate, as it is immunosuppressive, and promotes proliferation. Here, we will develop reporters for multiple types of cell death, senescence, and inflammation. Using these, we will carry out CRISPR-Cas9 screens to identify genes regulating these cell fates. Candidates will then be characterised using state-of-the-art microscopy, cell biology and mass-spectrometry techniques. Ultimately, we will describe mechanisms of cell fate responses that can be exploited for targeted therapy.