Extracellular regulation of TGFbeta signalling: essential for normal development and dysregulated in disease (e.g. cancer)

Cell signalling pathways play essential roles in human development and disease. One major signalling pathway, the transforming growth factor (TGF)-β family, plays crucial roles in embryonic development, adult tissue homeostasis and the pathogenesis of a wide-range of diseases from fibrosis to tumour invasion. Therefore, it is critical to understand the different ways in which the TGFβ pathway is regulated, in order that therapeutic strategies can be developed in the future. Research in my lab uses a multi-technique approach to understand the extracellular regulation of growth factors, including TGFβ and bone morphogenetic protein (BMP), which constitute a subclass within the TGFβ family. We know that growth factors are regulated by protein antagonists which bind and inhibit them outside the cell, as well as proteases which liberate the growth factors from inhibitory complexes. A variety of structural, biochemical and biophysical approaches will be used to investigate how these molecules interact and impact upon growth factor function. These findings are directly relevant to understanding growth factor dysregulation in diseases such as Marfan syndrome, cancers and bone disorders. This project offers a unique opportunity to be trained in structural, molecular, and biochemical techniques. Moreover, a structural understanding of how these regulators function will be useful for the development of novel medical strategies and therapeutics.