PhD position (Ageing & Disease): Role of the deubiquitylating enzyme CYLD in inflammation and ageing (m/f/d)
Thinking of doing your PhD in the Life Sciences? The Science of Healthy Ageing Research Programme (SHARP) is offering talented, young scientists the chance to work on cutting edge research projects and join a community of exceptional, international scientists. SHARP is a newly established research initiative between the Institute of Molecular Biology (IMB), Johannes Gutenberg-University (JGU) and JGU’s University Medical Centre (UMC) in Mainz. SHARP combines clinical and basic research to promote strategies towards healthy ageing, thereby further enforcing healthy ageing as a research focus in Mainz. As a SHARP PhD student you will be affiliated with both IMB’s International PhD Programme (IPP) and UMC’s Mainz Research School of Translational Biomedicine (TransMed) to ensure complementary training in both basic and translational research.
Activities and responsibilities:
In the fields of “Ageing & Disease”, the research group of Prof Ari Waisman and Prof Helle Ulrich jointly offer the following PhD project:
Chronic inflammation is a source of many ageing-related problems, including cancer, obesity, cardiovascular and neurological diseases. Proper control of the pro-inflammatory NF-κB signaling pathway is key to preventing uncontrolled inflammation and premature ageing. A major regulator of this pathway is the ubiquitin system. Ubiquitin as a posttranslational modifier is known for inducing protein degradation, but also acts in many non-proteolytic ways by modulating the localization or interactions of its targets. The NF-κB pathway is controlled by a deubiquitylating enzyme that removes Lys-63-linked ubiquitin chains from IkB kinase signaling components and thereby inhibits NF-kB signaling. The enzyme is encoded by a tumor suppressor gene, CYLD, that is mutated in familial cylindromatosis, an autosomal dominant predisposition to multiple tumors of the skin appendages. Mutations of CYLD in mice result in high susceptibility to tumor development and inflammatory diseases. Furthermore, we have shown recently that CYLD is involved in the development of neurological dysfunction, but the exact mechanism of function of CYLD in the brain is not clear.
PhD Project: Role of the deubiquitylating enzyme CYLD in inflammation and ageing
The Waisman lab uses molecular and genetic methods to study the function of CYLD in vivo. We have found that CYLD is important for the function of different immune cells, including B and T cells as well as dendritic cells. Recently, we have also shown that mice lacking CYLD show neurological dysfunctions, similar to what is observed in mouse models for autism. The Ulrich lab studies the mechanism of ubiquitylation in a variety of cellular processes. The combination of in vivo studies in the Waisman lab together with the molecular and biochemical work of the Ulrich lab should allow us a better understanding of the function of CYLD and its action as a deubiquitylating enzyme in the context of inflammation, neurological dysfunction, cancer and ageing.
In the frame of the SHARP grant the Waisman and Ulrich labs will cooperate to better understand the role of CYLD in inflammation and neurological functions. The PhD student will analyze mice with germline or tissue-specific deletions or overexpression of CYLD in models of inflammation and investigate how CYLD contributes to age-related manifestations that could be enhanced by hyper-activation of the NFkB pathway. On the molecular level, the student will identify and analyze relevant targets of CYLD to gain insight into the mechanism by which the deubiquitylating enzyme exerts its functions. In addition, we will analyze the signaling complexes involved in the NF-kB pathway to understand how CYLD regulates this pathway. This interdisciplinary project will be performed in collaboration between the two labs and the student will therefore receive training in a broad range of research tools, ranging from the analysis of mice to techniques in molecular and cell biology.
If you are interested in this project, please select Ari Waisman as your group preference in the IPP application platform.
What we offer:
Are you an ambitious, young scientist looking to push the boundaries of research while interacting with colleagues from multiple disciplines and cultures? Then joining SHARP is your opportunity to give your scientific career a flying start!
We seek enthusiastic applicants with a special interest in pursuing ageing research projects from bench-to-bedside.
All you need is:
For more details on the projects offered and how to apply via our online form, please visit https://www.imb.de/phd
The deadline for registration is 26 November 2021. Interviews will take place online 17-19 January 2022.
Starting date: 1 March 2022 – 1 September 2022
Tagged as: Life Sciences
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