The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) is one of the world’s leading biomedical research institutions. Max Delbrück, a Berlin native, was a Nobel laureate and one of the founders of molecular biology. At the MDC’s locations in Berlin-Buch and Mitte, researchers from some 60 countries study human biology – investigating the foundations of life from its most elementary building blocks to systems-wide mechanisms. By understanding what regulates or disrupts the equilibrium of a cell, an organ, or the entire body, we can prevent diseases, diagnose them earlier, and stop their progression with tailored therapies. To enable timely application of research findings for improving human health, the MDC supports entrepreneurship and participates in collaborative networks. The MDC has a close partnership with the Charité - Universitätsmedizin Berlin in the jointly run Experimental and Clinical Research Center (ECRC), the Berlin Institute of Health (BIH) at Charité, and the German Center for Cardiovascular Research (DZHK). Founded in 1992, the MDC today employs 1,600 people and is funded 90 percent by the German federal government and 10 percent by the State of Berlin.
Chronic hypertension causes annually 8.5 million deaths per year worldwide and causes end-organ damage, e.g. in heart and kidney. We have identified mutations in the gene encoding phosphodiesterase 3A (PDE3A) that cause hypertension with brachydactyly E (HTNB). The patients have severe hypertension, but surprisingly are protected from hypertension-induced end organ damage.
The aim of the project is:
1. elucidation of the molecular mechanisms underlying the hypertension
2. identification of the common mechanisms that protect the heart and the kidney from hypertension-induced damage.
1. Maass PG et al. PDE3A mutations cause autosomal dominant hypertension with brachydactyly. Nat Genet. 2015;47:647-53.
2. Ercu M et al. Phosphodiesterase 3A and Arterial Hypertension. Circulation. 2020;142:133-149.
3. Ercu M et al. Mutant Phosphodiesterase 3A Protects From Hypertension-Induced Cardiac Damage. Circulation. 2022; 146: 1758-1778
Postdoctoral position in compartmentalized cAMP signaling at the Max Delbrück Center in Berlin
PDE3A controls pools of cAMP in defined cellular compartments. Our HTNB-causing PDE3A mutants display altered activity and localisation (3,4) A major goal of the project is therefore to characterise the PDE3A signalling compartments in VSMCs as well as in kidney cells and cardiac myocytes. The ultimate aim of the project is to establish novel concepts for the treatment of hypertension and the hypertension-induced diseases such as heart failure and chronic kidney disease, i.e. a cAMP compartment-specific pharmacology directed at modulation of select protein-protein interactions with small molecules.
Methodologically, the project involves imaging technologies such as FRET, single cell genomics technologies, biochemical and proteomics approaches, targeting PDE3A and its protein-protein interactions with novel peptidic and non-peptidic pharmacological agents. Moreover, we have CRISPR/Cas9-generated PDE3A rat models with hypertension and brachydactyly available.
The project is multidisciplinary involving molecular pharmacology, molecular and cell biology, and animal physiology. The successful applicant is expected to drive their project in an independent manner in the context of a highly motivated team.
Experience in microscopy, in particular FRET, RNAseq and/or animal experimentation would be a plus.
- International working environment with communication in English and German
- Interesting career opportunities and a comprehensive range of qualification and further training opportunities
- Compatibility of family and career certified by the berufundfamilie audit
- Varied support for "New Berliners" (Welcome & Family Office)
- Company health management with fitness center
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
- A secure job, even in uncertain times
- Subsidy for the job ticket as well as discounts in the campus canteen
- Additional health benefits such as flu vaccination, eye test, ergonomics advice at the workplace, hygiene measures (medical mouth-nose protection, self-tests, disinfectants)
- The possibility of mobile working - also independent of the Corona situation
- Free use of Nextbike from the Buch S-Bahn station to the campus