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Posttranslational regulation of membrane proteins in health and disease
Germany (bvmd) - Christian-Albers-Universitaet, Kiel
Biochemical Institute, University of Kiel, Otto-Hahn-Platz 9, 24118 Kiel, Germany
Prof. Dr. Christoph Becker-Pauly
Prof. Dr. Christoph Becker-Pauly
Type of Research Project
- Basic science
What is the background of the project?
The most decisive posttranslational modification of membrane proteins, such as the amyloid precursor protein (APP) or the interleukin-6 receptor (IL-6R), is proteolytic trimming. For APP this can have beneficial or detrimental effects on neurons, defined as the non-amyloidogenic or amyloidogenic pathway. Upon shedding, the soluble IL-6R induces trans-signaling on a distinct cell in complex with the β-receptor gp130, a process that has strong pro-inflammatory activity. We and others have shown that both APP and IL-6R can be cleaved by the ADAM and meprin metalloproteases. However, the orchestration of competitive substrate-protease interactions within microdomains of cellular membranes and the impact of posttranslational modifications (PTMs) of these enzymes is enigmatic and will be investigated in this projec
What is the aim of the project?
Our aim is to unravel membrane associated interactors of meprins and ADAMs that specifically regulate the physical access to APP and IL-6R in health or disease. Examples of regulatory membrane proteins involved in this process are tetraspanins (TSPANs) that can interact with ADAM10 and, as demonstrated by us for TSPAN8, with meprin β. In more detail, we will investigate PTMs, such as glycosylation, phosphorylation and palmitoylation, of meprin β with regard to enzyme-substrate-orchestration at the plasma membrane.
What techniques and methods are used?
Our goal is to elucidate the candidate proteins and decisive PTMs involved in the hierarchical formation and orchestration of membrane protein clusters relevant for APP and IL-6R homeostasis by secretases. Therefore, we will employ well-established biochemical, proteomic, and cell biological approaches as well as mouse models, to identify so far unknown modes of membrane protein regulation as possible therapeutic windows for neurodegeneration and chronic inflammation.
What is the role of the student?
What are the tasks expected to be accomplished by the student?
The candidate will learn different biochemical approaches, such as : - SDS-PAGE for protein visualization - Western blot for protein identification - ELISA - Transient cell transfection - Immunfluorescence microscopy - Enzyme activity assay (fluorescence-based) - Enzyme inhibition studies The tutor of the project will talk with the incoming students before the exchange about their previous experiences and knowledge and decide on specific tasks according to that.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
There will be weekly lab seminars about ongoing projects and experimental details.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a scientific report - No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
High motivation is mandatory. Excellent biomedical background and laboratory experience is preferable.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Students in biomedical fields
- Schönherr et al.; 2016; Molecular Neurodegenration Wichert et al.; 2017; Cell Reports
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