Delineating late foetal human lung development and maturation

我们对肺是如何发育的理解非常差。解决这个问题真的很重要，因为我们可以研究出如何帮助早产儿，以及如何再生肺来帮助那些患有严重肺部疾病的人。任何原因的终末期肺部疾病都是一个重大的全球健康问题。另一方面，早产的死亡率和问题主要是由于肺太不成熟或发育不充分而不能发挥作用，而不是健康的足月儿。尽管使用了一些治疗方法，如类固醇，但这并不能克服早产对成人肺功能的长期影响。我已经有了重要的发现来了解肺的发育。这是利用怀孕后20周的人类胚胎和胎儿肺制作的--值得注意的是，我开发了一种3D培养系统，可以用来在培养皿中研究人类肺的发育。我的工作还包括免疫细胞如何使用各种尖端的分子方法与发育中的肺相互作用，这些方法可以单独观察每个细胞。出生20周后的发育期几乎没有被探索过，在科学界被称为“鸿沟”。在与产科医生和伦敦大学学院的其他医生的密切合作下，我设计了一种方法，可以从怀孕最后阶段这一关键发育时期的任何器官获得新鲜的健康组织。我的目标将是1)研究肺壁如何成熟，2)研究免疫系统如何在肺内以及身体其他部位成熟，3)研究血管如何成熟，以及它们如何与肺壁相互作用，形成一个正常运作的气体交换单元，使氧气能够被输送到血腔，二氧化碳被转移到空气腔，最后，4)为其他致力于其他器官成熟的研究小组建立晚期胎儿组织资源。我的总体目标是研究晚期胎儿肺的发育和成熟，这可能会对各个领域产生广泛影响，最显著的是提高早产儿的存活率，并找到扭转严重肺部疾病影响的方法。

Our understanding of how the lung develops is very poor. Addressing this is really important because we can work out how to help premature babies and how to regenerate lungs to help those with severe lung disease. End-stage lung disease of any cause is a major global health problem. On the other hand, the death rate and problems arising from premature birth are mostly caused by the fact that the lung is too immature or underdeveloped to function as opposed to in healthy term babies. This is despite the use of some treatments such as steroids which do not overcome the long-term effects of premature birth on lung function as an adult. I have already made important discoveries to understand lung development. This was made using human embryonic and foetal lungs up to 20 weeks post-conception - notably I have developed a 3D culture system which can be used to study human lung development in a dish. My work also includes how immune cells interact with the developing lung using various, cutting edge molecular methods that can look at each cell individually. The period of development after 20 weeks to birth is virtually unexplored and is referred to as the "gap" in the scientific world. In close collaboration with obstetricians and other doctors at UCL, I have designed a way of receiving fresh healthy tissue from any organ from this crucial period of development during the final part of pregnancy. My aims will be 1) to study how the lining of the lung matures, 2) to study how the immune system matures within the lung and also elsewhere in our body, 3) to study how blood vessels mature and how they interact with the lung lining to make a functioning gas exchange unit, allowing oxygen to be transported into the blood compartment and carbon dioxide to be transferred into the air compartment, and finally 4) to set up a late foetal tissue resource for the other research groups working on the maturation of other organs. My overall objective is to study late stage foetal human lung development and maturation, which has the potential for wide-reaching impact on various fields, most notably to improve survival in premature babies and to find ways to reverse the effects of severe lung disease.