Investigating the mechanosensitive interplays between genetic control and self-organisation during the emergence of cardiac tissue curvature

研究心脏组织曲率出现过程中遗传控制和自组织之间的机械敏感性相互作用

• 批准号: BB/Y00566X/1
• 负责人: Julien Vermot
• 金额: $ 175.3万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY00566X%2F1
• 关键词: Investigating; mechanosensitive; interplays; between; genetic

Cardiovascular Diseases (CVDs) are the leading causes of death in the world. Congenital heart malformations account for as many as 30% of embryos or foetuses lost before birth. To properly develop, the heart needs to generate mechanical forces during the growth of the whole structure. This, in combination with genetic information, is required for assembling a functional heart. Currently, most studies focus on how genetic programmes control cell identities and their subsequent roles in cardiac development. In contrast, the mechanical forces that are integral to the growth and assembly of the heart are much less explored. This is surprising as abnormal mechanical forces can deregulate gene expression and lead to diseases such as congenital heart disease and cardiomyopathies. Understanding how biomechanics regulates cardiac morphogenesis is thus of utmost importance. This project will explore the interplay between genetic control and self-organization emerging from cell mechanics during cardiogenesis. Our hypothesis is that mechanotransduction is at the centre of this interplay. We will study the role of mechanotransduction in the emergence of multicellular flow and the mechanism of a newly characterized cell shape change associated with cardiac chamber morphogenesis.

心血管疾病（cvd）是世界上主要的死亡原因。先天性心脏畸形在出生前丢失的胚胎或胎儿中占30%之多。为了正常发育，心脏需要在整个结构的生长过程中产生机械力。这与遗传信息相结合，是组装功能性心脏所必需的。目前，大多数研究集中在遗传程序如何控制细胞身份及其在心脏发育中的后续作用。相比之下，对心脏生长和组装不可或缺的机械力的探索要少得多。这是令人惊讶的，因为异常的机械力可以解除基因表达的调节，导致先天性心脏病和心肌病等疾病。因此，了解生物力学如何调节心脏形态发生是至关重要的。本项目将探讨基因控制与心脏发生过程中细胞力学产生的自组织之间的相互作用。我们的假设是，机械转导是这种相互作用的中心。我们将研究机械转导在多细胞血流出现中的作用，以及与心室形态发生相关的新特征细胞形状变化的机制。