Project description
Dissecting TGF-β signalling in health and disease
Transforming growth factor beta (TGF-β) is a cytokine with multiple functions, encountered in different isoforms and expressed by various cell types. Deregulation of the TGF-β pathway is responsible for many human diseases including cancer, with recent evidence implicating TGF-β in the tumour microenvironment and in cancer immunotherapy. The aim of the EU-funded TGF-BTB project is to provide mechanistic insight into TGF-β signalling. For this purpose, scientists will combine structural and cell biology methods with in silico approaches and develop new tools to study the impact of pathway manipulation. Results will not only shed light on unexplored aspects of TGF-β signalling but also open new therapeutic avenues for treating diseases.
Objective
TGF-BTB (Transforming Growth Factor – Bench To Bedside) is an ambitious and innovative project, the goal of which is to not only to understand the different roles of the TGF-β isoforms as well as in cell signalling at a molecular level, but also to explore their critical roles implicated in pathogenesis of fibrotic disorders and cancer. The dysregulation or complete shutdown of TGF-β pathway is responsible for many human diseases including connective tissue disorders, fibrotic disorders and the initiation and progression of soft tissue cancers. Most recent data show the importance of TGF-β in controlling the tumor microenvironment and its significance in the course of anticancer immunotherapies. The project will employ methods of structural and cell biology, together with in silico simulations, and will include the development of new tools, such as isoform-specific peptide-based inhibitors, engineered cytokines to study and manipulate the TGF-β canonical and non-canonical pathways. TGF-BTB is not only of great importance for increasing basic mechanistic understanding of TGF-β signalling, but also in terms of discovering potential new therapeutic avenues for treating diseases driven by excessive TGF-b signaling. During the outgoing phase, The Fellow, Dr Łukasz Wieteska, will join Prof Andrew Hinck’s research group at the University of Pittsburgh, which is a world class research laboratory at the forefront of TGF-β family structural studies. the Fellow will return to the University of Leeds to continue his work with Prof John Ladbury, whose research has a strong focus on exploring the structural, biophysical, and cellular outcomes of the interplay of protein receptors in cell signalling pathways. Upon return, the Fellow will also benefit from a secondment at The Francis Crick Institute in the laboratory of Dr Caroline Hill, a leading researcher in the field of developmental biology with a special focus on TGF-β signaling.
Fields of science
- natural sciencesbiological sciencescell biologycell signaling
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesdevelopmental biology
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicineimmunologyimmunotherapy
Keywords
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
LS2 9JT Leeds
United Kingdom