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Transforming Growth Factor – Bench To Bedside. Towards a better understanding of TGF-β isoform specific signalling in health and disease

Descrizione del progetto

Analizzare la segnalazione del TGF-β in salute e malattia

Il fattore di crescita trasformante beta (TGF-β) è una citochina con molteplici funzioni, riscontrata in diverse isoforme ed espressa da vari tipi di cellule. La deregolamentazione della via del TGF-β è responsabile di molte malattie umane, compreso il cancro, e recenti evidenze coinvolgono il TGF-β nel microambiente tumorale e nell’immunoterapia del cancro. L’obiettivo del progetto TGF-BTB, finanziato dall’UE, è quello di fornire una valutazione meccanicistica della segnalazione del TGF-β. A tale scopo, gli scienziati combineranno metodi di biologia strutturale e cellulare con approcci in silico e svilupperanno nuovi strumenti per studiare l’impatto della manipolazione della via di segnalazione. I risultati non solo chiariranno aspetti inesplorati della segnalazione del TGF-β ma apriranno anche nuove strade terapeutiche per il trattamento delle malattie.

Obiettivo

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.

Coordinatore

UNIVERSITY OF LEEDS
Contribution nette de l'UE
€ 271 732,80
Indirizzo
WOODHOUSE LANE
LS2 9JT Leeds
Regno Unito

Mostra sulla mappa

Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 271 732,80

Partner (1)