Understanding the molecular and biophysical mechanisms that drive cell contact re-establishment after division

了解分裂后驱动细胞接触重建的分子和生物物理机制

• 批准号: 2577765
• 金额: --
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2577765
• 关键词: Understanding; molecular; biophysical; mechanisms; drive

Cells are generally not found in isolation, but embedded within tissues. Therefore, after every cell division the newly formed cells need to re-establish cell-cell contacts to maintain tissue integrity. The inability to coordinate cell division and cell contact re-establishment can lead to developmental disorders, for example those characterised by a variety of birth defects. Despite its importance in tissue homeostasis, the mechanisms controlling the formation of cell-cell contacts immediately after cell division remain poorly understood. To identify genes involved in contact re-establishment, we will use our large-scale genetic screen in C. elegans. This screen identified regulators of early embryonic developmental processes, mainly: cell division, cytoskeleton dynamics and membrane composition/organisation. Following this screen, we will design a comprehensive phenotypic analysis to identify genes involved in cytokinesis, which is the process that completes cell division. In collaboration with our partner "Intogral" we will perform quantitative image data analyses upon loss of function of the identified cytokinesis regulators. This will help us determine key biomechanical parameters required for contact re-establishment during cytokinesis. We will use this data to train a computational model to identify early signs of tissue integrity problems. In addition, the molecular characterization of the identified cytokinesis regulators will advance our understanding of the mechanisms that coordinate cell contact re-establishments with other key processes during embryogenesis, for example cell orientation and polarity.

细胞通常不是孤立存在的，而是嵌入组织中。因此，每次细胞分裂后，新形成的细胞需要重新建立细胞间的接触，以保持组织的完整性。无法协调细胞分裂和细胞接触重建可能导致发育障碍，例如以各种出生缺陷为特征的发育障碍。尽管其在组织内稳态中的重要性，但控制细胞分裂后立即形成细胞-细胞接触的机制仍然知之甚少。为了鉴定参与接触重建的基因，我们将在C.优雅的该筛选确定了早期胚胎发育过程的调节因子，主要包括：细胞分裂、细胞骨架动力学和膜组成/组织。在这个筛选之后，我们将设计一个全面的表型分析来鉴定参与胞质分裂的基因，胞质分裂是完成细胞分裂的过程。在与我们的合作伙伴“Intogral”的合作中，我们将在确定的胞质分裂调节因子功能丧失后进行定量图像数据分析。这将帮助我们确定细胞质分裂期间接触重建所需的关键生物力学参数。我们将使用这些数据来训练计算模型，以识别组织完整性问题的早期迹象。此外，所鉴定的胞质分裂调节剂的分子表征将促进我们对在胚胎发生期间协调细胞接触重建与其他关键过程（例如细胞取向和极性）的机制的理解。