1 PhD project offered in the IPP winter call 2020/2021
Organismic ageing is accompanied by changes in the level of DNA cytosine methylation. These changes are so stereotypic that “epigenetic clocks’ have been developed, whose methylation level tightly correlates with biological age, most famously ‘Horvath’s clock’. These epigenetic clocks predict biological age and inform about positive or negative deviation of biological from chronological age, as well as predicting time to death.
In an interdisciplinary project, we will investigate the utility of Horvath’s clock in studying the common age-associated disease of heart failure (HF), a syndrome that shows growing prevalence due to increasing life expectancy and demographic change. HF represents a high medical and economic burden and is the most frequent cause of hospitalization. There are distinct HF-phenotypes with varying outcome, the mechanisms of which are poorly understood. To stratify HF and predict patient outcomes we will employ Horvath’s clock as a molecular parameter.
In this project, you will establish the computational analysis employing Horvath’s clock and use it to calculate the epigenetic age a cohort of HF patients. You will correlate epigenetic age with available clinical parameters to stratify patients, predict disease outcome, and develop computational tools that improve treatment regimes. The project will be pursued in close collaboration with Prof. Philipp Wild at the University Medical Center (Preventive Cardiology). The successful candidate will have a strong background in Computational Biology, Bioinformatics, and/or Epidemiology.
Publications relevant to this project
Schäfer A, Mekker B, Mallick M, Vastolo V, Karaulanov E, Sebastian D, von der Lippen C, Epe B, Downes DJ, Scholz C, and Niehrs C. (2018) Impaired DNA demethylation of C/EBP sites causes premature aging. Genes Dev. 32:742-762.
Schuster AK, Leuschner A, Feretos C, Blumenstein P, Troebs SO, Schwuchow S, Schulz A, Nickels S, Mirshahi A, Blettner M, Beutel ME, Lackner KJ, Münzel T, Pfeiffer N, Wild PS (2020) Choroidal thickness is associated with cardiovascular risk factors and cardiac health: the Gutenberg Health Study. Clin Res Cardiol. 109:172-182.