Tribbles Research and Innovation Network

ended

This proposal was developed in the context of the medical need to tackle the clinical consequences of obesity-related diseases more holistically. Dysregulation of common molecular pathways that govern the physiological functioning of adipocytes, immune cells and prostate epithelium cells have been reported in immuno-metabolic disease (such as obesity) and several cancers. The individual projects described in the proposal will investigate regulators of these pathways with a focus on a recently described family of pseudokinases, namely tribbles proteins, which have a key role in controlling immunity, metabolism and cancer, and which here will serve as prototypical examples for integrative metabolocentric cancer research. Tribbles are envisaged to contribute directly to the development and progression of prostate cancer, the prognosis of which is substantially worsened in individuals with immuno-metabolic disease. We therefore propose a multidisciplinary research-training programme with an overall objective to uncover cell-specific aspects of tribbles-mediated control of immuno-metabolism and their impact on prostate cancer progression. We will approach this by integrating cell biology and sophisticated in vivo models of both immuno-metabolic disease and prostate cancer, complemented by specialist human disease biobanks, cutting-edge genomics approaches, plus a drug discovery pipeline. This will be carried out by an alliance of leading academic research groups and specialist SMEs with complementary backgrounds in inflammation, adipose tissue biology, tumourigenesis, genomics, translational models of human disease, medicinal chemistry and drug discovery. This will provide a unique opportunity for a cohort of PhD students to undertake Research Training at the interface of several disciplines and sectors, thereby gaining a diverse portfolio of R&D expertise and transferrable skills as well as exposure to several non-academic career pathways.