Mechanisms of intestinal innervation and vascularization

作为人体与外界的第一道屏障，消化道在分解食物、吸收营养和提供抵御有害细菌的第一道防线方面发挥着至关重要的作用。两个复杂的系统确保所有这些重要功能都适应我们身体的需求：控制肠道收缩和分泌的神经系统，以及向细胞输送氧气的血管系统。氧供应异常和/或肠神经功能障碍可导致普遍的，有时危及生命的疾病，如肠缺血，先天性巨结肠症和肠易激综合征。这些情况强调了神经、血管和消化系统之间相互作用的重要性。他们还强调需要了解这三个系统如何正常互动，以及当事情出错时会发生什么。这项研究计划旨在确定确保这三个系统之间正常相互作用的分子。特别是，我们想了解神经细胞和组成血管系统的分支如何设法找到并与肠道接触，以及神经和血管系统是否相互交谈以实现这一目标。了解这个过程通常是如何发生的，将有助于我们了解当神经细胞和血管系统无法正确连接到肠道时会出现什么问题。例如，我们鉴定的分子很可能在上述条件下不存在。在这种情况下，我们可以设计方法将它们输送给患者，以促进他们的消化道与神经细胞和/或血管系统之间形成新的连接。

As the human body's first barrier to the outside world, the digestive tract plays an essential role in breaking down food, absorbing nutrients and providing a first line of defence against harmful bacteria. Two complex systems ensure that all these important functions are adapted to the needs of our body: the nervous system, which controls the contractions and secretions of the gut, and the vascular system, which delivers oxygen to its cells. Abnormal oxygen supply and/or the malfunction of gut nerves can lead to prevalent and, sometimes life-threatening conditions, such as intestinal ischemia, Hirschsprung's disease and irritable bowel syndrome. These conditions underscore the importance of the interaction between the nervous, vascular and digestive systems. They also highlight the need to understand how these three systems interact normally, and what happens when things go wrong. This research proposal aims to identify the molecules that ensure the normal interaction between the three systems. In particular, we want to understand how nerve cells and the branches that make up the vascular system manage to find and make contact with the gut, and whether the nervous and vascular systems talk to one another to achieve this goal. Understanding how this process occurs normally will help us understand what goes wrong when nerve cells and the vascular system fail to connect to the gut properly. For example, it may well be that the molecules we identify are not present in the conditions mentioned above. In that case, we could devise ways to deliver them to patients to promote the formation of new connections between their digestive tract and their nerve cells and/or vasculature.