The role of the Frem proteins in development and disease

罕见的遗传疾病通常可以为我们提供一些控制我们如何发展和健康生活的基本机制的见解。我们已经确定了一个叫做Fras和Frem的基因家族，其中一些基因在一种叫做弗雷泽综合征的疾病中发生了突变。弗雷泽综合征患者的皮肤和肾脏的正常发育存在严重缺陷。我们正在研究这些基因的功能，不仅是为了了解弗雷泽综合征是如何发展的，也是为了了解我们的器官是如何正常发育的。与FS有关的基因有助于细胞外基质的形成，细胞外基质实际上是细胞发育成器官时使用的支架。细胞外基质在维持我们的成人组织和对损伤作出反应方面也很重要。它可以作为一种物理支持，并作为我们的细胞如何对生长因子和彼此作出反应的关键控制器。该提案将探索Fras和Frem基因如何介导这些相互作用来控制正常发育，并确定它们的突变如何引起疾病。通过这样做，我们希望深入了解影响肾脏和皮肤的更常见的疾病。

Rare genetics diseases can often provide us with insights into some of the fundamental mechanisms which control how we develop and live healthy lives. We have identified a family of genes called the Fras and Frem genes and some of these are mutated in a disorder called Fraser Syndrome. Fraser Syndrome patients have profound defects in the normal development of their skin and kidneys. We are studying the function of these genes with a view to understanding not just how Fraser Syndrome develops, but how our organs develop normally. The genes involved in FS contribute to the extracellular matrix which is effectively the scaffolding which our cells use when developing into our organs. The extracellular matrix is also important in maintaining our adult tissues and responding to damage. It can act as a physical support and as a key controller of how ours cells react to growth factors and to each other. This proposal will explore how the Fras and Frem genes mediate these interactions to control normal development and also to determine how their mutation gives rise to disease. In doing so we hope to gain insights into more common diseases which affect both the kidney and the skin.