Glucocorticoids bind the glucocorticoid receptor to control immune responses and to drive metabolic pathways. Industry has developed synthetic variants of glucocorticoids, this to battle inflammation and cancer. However, chronic use hereof leads to quality-of-life-threatening side effects and to therapy resistance. The glucocorticoid receptor, which is also a transcription factor, is an intriguing protein as the structure of this multi-domain protein dynamically responds to its immediate environment including small molecules, other proteins and binding motifs present in the DNA structures it recognizes. As a result, several research programs focus on understanding the molecular mechanisms steering the receptor’s structures and on developing small molecules that drive this receptor into its most optimal structure in terms of beneficial effects for patients under (synthetic) glucocorticoid treatment.
In a proof-of-concept study, our labs have shown that the structural plasticity of the receptor can be revealed by proteomics, albeit in an in vitro setup. Now, we will develop a controllable technology in which a promiscuous protease is activated in living cells to then introduce cuts in surface-accessible regions of proteins in their natural environment. Comparative analysis using different small molecules modulating the glucocorticoid receptor to align a proteomics read-out with functional validations in cellulo must reveal how the receptor’s structure is controllable in its natural environment.
- The candidate should hold a relevant Master degree in the field of life sciences (e.g., biotechnology, biochemistry, biomedical sciences, bio-engineering, molecular biology, …).
- The candidate must meet all eligibility criteria to apply for a personal FWO PhD fellowship, see https://www.fwo.be/en/fellowships-funding/phd-fellowships/phd-fellowship-strategic-basic-research/.
- The candidate, helped by his/her supervisors, must write a PhD project application (deadline February 2021).
- Hands-on experience with cloning, protein expression or mass spectrometry-driven proteomics are considered important assets.
Key personal characteristics
We will hire an enthusiastic, warm and motivated young scientist who considers science as his/her playground! You should have a keen interest in the underlying biology of inflammatory diseases and in technology building tools, good communication and writing skills (English), and should be able to work independently, as well as function as part of a multidisciplinary team. You must be able to communicate with proteome scientists, operators of mass spectrometers, bioinformaticians and statisticians.
We offer a position for 1 year with the possibility of extension to 4 years in case of a positive FWO/BOF-application. The candidate will have to apply for an FWO PhD-fellowship in February 2021. He/she will work in a stimulating multicultural environment and gain expertise in two high-level laboratories, more precisely the proteomics lab of Prof. Dr. Kris Gevaert and the molecular mechanism-oriented lab from Prof. Dr. Karolien De Bosscher. In addition, he/she will have access to cutting-edge technologies, personal career assistance and high-level training courses. The position is available from the autumn of 2020.
How to apply?
Motivated candidates are asked to apply online.