GRK 1816:  Phosphorylation- and Redox-mediated Signalling Mechanisms in the Failing Heart

• Subject Area: Medicine
• Term: from 2013 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 200857327

Cardiovascular disease and cancer represent the two leading causes of death in the Western World. Still, cardiovascular disease causes more deaths and more hospitalizations than cancer and heart failure is one of the most common reasons for hospital admissions among those 65 years and older. However, this condition is not restricted to the elderly. Aetiologies leading to heart failure are diverse including vascular and valve dysfunctions, hypertension, arrhythmias, genetic mutations, infections, and many more. In every case the result is a progressive damage of the heart impairing its fundamental function. Reversing this process is still not possible due to several reasons. During the progression of the disease the number of muscle cells in the heart become progressively fewer and the ability of the heart to substitute this loss by newly produced cardiomyocytes is very low. Instead a repair mechanism is induced which intends to stabilize the heart tissue. This involves the overt production of extracellular matrix proteins, which function as a cell glue, by cardiac fibroblasts. This glue, however, negatively influences the physical muscle function. The whole process is called cardiac remodelling. The driving force of cardiac remodelling is a change in communication between and in the different heart cells. In every cell thousands of proteins are involved in converting a received message into a cell response. On a molecular level communication in a cell includes the short- or long-term modification of signal mediators, which can be, but have not to be reversible. Amongst these, phosphorylation- and redoxdependent modifications of proteins are the vast majority. Often protein modifications are considered to function as simple switches, turning a protein on or off. Today, we know that most proteins are not only modified at one position but at several and in multiple ways, and all these changes are integrated in one response. Moreover, when and where a protein is modified is similarly important. This makes the analysis of protein modifications particularly challenging. The aim of the IRTG 1816 is to decipher the role of phosphorylation- and redox-dependent modifications of proteins in the setting of heart disease. Therefore, the University Medical Centre Göttingen and the King's College London have joined forces and combined their scientific expertise in altogether 12 research projects to efficiently answer urgent open questions and thus to lay the basis for future therapeutic options for heart failure. Moreover, this unique collaboration is a powerful education training programme. We believe that investing in the education of international young scientists (Medical students and doctoral researchers of the natural sciences) with the help of a structured programme is an important investment in the future of cardiovascular science.

• DFG Programme: International Research Training Groups
• International Connection: United Kingdom
• Applicant Institution: Georg-August-Universität Göttingen
• IRTG-Partner Institution: King's College London
• Spokesperson: Professorin Dr. Dörthe M. Katschinski
• Participating Researchers: Professor Dr. Ivan Bogeski; Professor Dr. Tobias Brügmann, since 1/2020; Professor Dr. Gerd Hasenfuß; Professor Dr. Stephan E. Lehnart; Professorin Dr. Susanne Lutz; Professor Dr. Thomas Meyer; Professorin Dr. Blanche Schwappach-Pignataro; Professorin Dr. Katrin Streckfuß-Bömeke; Professor Dr. Wolfgang Niels Voigt; Professorin Dr. Elisabeth Zeisberg; Professor Dr. Wolfram-Hubertus Zimmermann
• IRTG-Partner: Spokesperson: Professor Ajay M. Shah