PhD position – Novel mechanisms of regulation of the ADAM17 metalloprotease for anti-inflammatory and anti-obesity strategies (IOCB Prague)

At the Institute of Organic Chemistry and Biochemistry of the CAS / IOCB Prague, we are looking for talented, independent, and highly motivated PhD students with an MSc. degree or equivalent in life sciences or related fields. We are offering more than 20 new exciting projects in organic and medicinal chemistry, biochemistry, molecular biology, analytical, and physical chemistry.

• Online registration deadline: 20 February 2023
• Interview Day: 23 March 2023

Learn more and apply at https://www.uochb.cz/en/call-for-phd-applications

The membrane anchored metalloprotease ADAM17 is a key regulator of growth factor and inflammatory cytokine production and as such has long been an attractive target for anti-cancer and anti-inflammatory strategies. However, the wide substrate repertoire and pleiotropic roles of ADAM17 in various tissues have made it a difficult target. Recently, novel transmembrane regulators of ADAM17 have been discovered, the iRhoms (Adrain et al Science 2011). These are required for the trafficking and maturation of ADAM17, its rapid activation at the cell surface, and for modulating its substrate repertoire. Since iRhom2 expression is maily limited to macrophages, the main source of the proinflammatory cytokine TNF, targeting iRhom2 would provide a novel way to target ADAM17 selectively in inflammation, sparing its other roles in other tissues.

This project, funded by the Czech Science Foundation, focusses on the intracellular protein partners of iRhom2, which are known to modulate iRhom2 activity and stability (Oikonomidi et al. eLife 2018), aiming to understand the involved mechanisms structurally, mechanistically and cell biologically at a detailed level, with the perspective of eventual translational outcomes.

The candidate would be a biochemist with a structural biology experience.

University: Faculty of Science, Charles University
Field of study: Biochemistry
Tutor: Kvido Stříšovský, Ph.D.
Group: Kvido Stříšovský Group – Intramembrane Proteolysis and Biological Regulation