Posdoc Anchored Signalling Group, Klussmann
Berlin-Buch | Max Delbrück Center
The Max Delbrück Center for Molecular Medicine in the Helmholtz Association aims to transform tomorrow’s medicine through our discoveries of today. At locations in Berlin-Buch, Berlin-Mitte, Heidelberg and Mannheim, our researchers harness interdisciplinary collaboration to decipher the complexities of disease at the systems level – from molecules and cells to organs and the entire organism. Through academic, clinical, and industry partnerships, as well as global networks, we strive to translate biological discoveries into applications that enable the early detection of deviations from health, personalize treatment, and ultimately prevent disease. First founded in 1992, the Max Delbrück Center today inspires and nurtures a diverse talent pool of 1,800 people from over 70 countries. We are 90 percent funded by the German federal government and 10 percent by the state of Berlin.
Arginine-vasopressin (AVP, antidiuretic hormone) induces water reabsorption in the renal collecting duct and thereby fine-tunes body water homeostasis. The binding of AVP to its receptor (V2R) leads to an accumulation of the water channel aquaporin-2 (AQP2) in the plasma membrane of collecting duct principal cells, which facilitates water reabsorption from primary urine. This water reabsorption is one of the critical components controlling body water homeostasis and blood pressure. Dysregulation of this system prevents the plasma membrane accumulation of AQP2 and causes the excessive loss of water, the major characteristic of diabetes insipidus. The millions of diabetes insipidus (DI) patients suffer from passing up to 20 l of hypotonic urine per day. The water loss leads to symptoms ranging from mild such as excessive thirst and cognitive dysfunction to severe such as hypotension, seizure, renal hypoperfusion or hypovolaemic shock. There is no satisfactory treatment DI available.
The project has two aims: 1) A major goal is the further development of already identified novel small molecules towards drug candidates for the treatment of diabetes insipidus. The molecules promote the plasma membrane localization of AQP2 independent of AVP and the V2R. 2) A second aim is to understand the mode of action of the new molecules, and thereby to elucidate molecular mechanisms controlling the localisation and trafficking of AQP2. This will improve our understanding of mechanisms directing water homeostasis and blood pressure. In addition, the trafficking of AQP2 resembles a cAMP-induced exocytosis; elucidating underlying molecular mechanisms will also shed light on other processes, such as renin secretion from juxtaglomerula cells or proton secretion in the stomach.
Job Description
The project is funded by the Federal Ministry for Education and Research (Bundesministerium für Bildung und Forschung, BMBF) and is a collaboration with the group of Prof. R. Süssmuth, Technical University Berlin. Together, we have initiated a medicinal chemistry and preclinical test programme for the development of novel antidiuretic compounds on the basis of the already identified molecules.
The chemistry will provide molecules.
We are looking for a highly motivated candidate to take on the characterisation of the novel compounds in our in vitroand in vivo systems.
Requirements
The candidate requires a strong life science background with interest in drug development. The project involves broad methodology: e.g. microscopic imaging techniques, target profiling by mass spec, target validation by siRNA and pharmacological modulation, characterisation of effects of molecules on principal cells in cell culture and in mice, in particular on AQP2.
We offer
- international working environment with communication in English and German
- interesting career opportunities and a range of opportunities for further qualification and training
- Compatibility of family and career certified by the workandfamily audit (“berufundfamilie audit”)
- Support for "New Berliners" through the MDC Welcome & Family Office
You also benefit from:
- a remuneration in accordance with the collective agreement for the federal public service (TVöD-Bund), including additional company pension schemes
- flexible working hours and childcare support
- an idyllic green campus, which is easily accessible by bicycle, public transport or car
- free use of Nextbike from the Buch S-Bahn station to the campus
- Subsidy for the job ticket as well as discounts in the campus canteen
- On-campus health and fitness center
- additional health benefits such as flu vaccination, eye test, ergonomics advice at the workplace
