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）是世界上死亡的主要原因。先天性心脏畸形占出生前失去的胚胎或胎儿的30％。为了正确发展，心脏需要在整个结构的生长过程中产生机械力。结合遗传信息，组装功能性心脏是必需的。当前，大多数研究都集中在遗传程序如何控制细胞身份及其随后在心脏发展中的作用。相比之下，探索了心脏生长和组装不可或缺的机械力。这是令人惊讶的，因为异常的机械力可以放大管制基因表达并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至关重要。该项目将探索心脏病发生过程中细胞力学出现的遗传控制与自组织之间的相互作用。我们的假设是机械转载是该相互作用的中心。我们将研究机械传导在多细胞流的出现中的作用以及与心脏腔形态发生相关的新表征的细胞形状变化的机制。