ABOUT THE PROJECT:

Drug repurposing is a fast and inexpensive strategy to reuse already approved drugs. This is especially useful in the context of diseases with limited therapeutic approaches. Actually, this therapeutic gap is present in the pharmacological management of Crohns disease (CD). CD is a chronic inflammatory condition that can affect any part of the intestinal tract. The intestinal inflammation is mediated by cytokine such as TNF-α, which plays a pivotal role in the intestinal destruction of these patients. Anti-TNF-α biologic drugs have become the gold standard for the pharmacological management of CD. However, owing to the characteristics of these drugs, 20 to 40% of patients are or become resistant to it. Therefore, it is mandatory to find alternative drugs that circumvent these limitations. Genome-wide association studies have uncovered several links between CD and autophagy. In this sense, research conducted in autophagy-deficient animals has shown an increased susceptibility of the intestinal epithelial cells to TNF-α-driven cell death.

The project will use a high-throughput screening to identify compounds exerting a cytoprotective effect against TNF-α-mediated cell death. The most suitable

candidate(s) will undergo a thorough characterization of their mechanism of action in the context of TNF-α-driven cell death. This work will be the a first-step in repositioning the selected candidate(s) for the pharmacological management of CD.

ABOUT THE CANDIDATE:

Año de obtención del título de grado: posterior a 2014

IMPORTANTE: Nota de grado superior a 8!

Por favor, incluir información relativa a la nota media de grado y de máster.