Starting as soon as possible at Department of Cardiology, Angiology and Pneumology.
The research group "Molecular and Translational Cardiology", headed by Prof. Dr. Patrick Most and Dr. Julia Ritterhoff, focuses on the underlying molecular causes of cardiovascular diseases and the targeted development and translation of molecular therapies for clinical applications in cardiovascular diseases.
The innovative research project focusses on the development and translation of a novel peptide therapy against cardiac diseases. It is based on extensive preliminary work by our working group, which has demonstrated therapeutic effects of the synthetic peptide in chronic and acute heart failure animal models.
The therapeutic peptide is derived from the protein S100A1, which plays a central role in maintaining normal heart function. The synthetic peptide (S100A1ct) mimics the function of the native protein in the heart muscle and, due to its pharmacokinetic and pharmacodynamic properties, can be used and further developed as a candidate for the experimental therapy of myocardial insufficiency.
The aim of the project is to develop additional cell-permeable S100A1ct peptidomimetics with extended therapeutic capabilities and investigate their cardioprotective effects in cardiac diseases models, such as anthracycline-induced cardiotoxicity (AICT) and heart failure with preserved/ reduced ejection model.
References:
Kehr D, Ritterhoff J, Glaser M, Jarosch L, Salazar R, Spaich K, Varadi K, Birkenstock J, Egger M, Gao E, Koch WJ, Katus HA, Frey N, Jungmann A, Busch CJ, Mather PJ, Ruhparwar A, Voelkers M, Wade RC, Most P: S100A1ct: a synthetic peptide derived from human S100A1 protein improves cardiac contractile performance and survival in pre-clinical heart failure models. Circulation. 2024 Nov 21. doi: 10.1161/CIRCULATIONAHA.123.066961. Online ahead of print.
Volkers M, Loughrey CM, Macquaide N, Remppis A, DeGeorge BR, Jr., Wegner FV, Friedrich O, Fink RH, Koch WJ, Smith GL, and Most P (2007) S100A1 decreases calcium spark frequency and alters their spatial characteristics in permeabilized adult ventricular cardiomyocytes. Cell Calcium 41: 135-143 doi: 10.1016/j.ceca.2006.06.001
Most P, Remppis A, Weber C, Bernotat J, Ehlermann P, Pleger ST, Kirsch W, Weber M, Uttenweiler D, Smith GL, Katus HA, and Fink RH (2003) The C terminus (amino acids 75-94) and the linker region (amino acids 42-54) of the Ca2+-binding protein S100A1 differentially enhance sarcoplasmic Ca2+ release in murine skinned skeletal muscle fibers. J Biol Chem 278: 26356-26364 doi: 10.1074/jbc.M303338200
Responsible planning and implementation of experiments within the framework of the scientific
project plan
Develop and establish new methods in the laboratory to enable new research approaches
Isolation of primary cardiomyocytes and analysis of contractility and calcium transients
Establishment of in vivo disease models to test therapeutic efficacy of S100A1ct and other S100A1-derived peptides
Interaction with collaboration partners/ core facilities and support other scientists in their research projects
Participation in scientific events with your own contributions is expressly desired
Completed university degree in natural sciences (specializing in biology, molecular medicine, cardiovascular sciences)
Sound knowledge in standard methodologies in molecular and cellular biology (e.g. primary cell culture, qPCR, WB, histology)
Experience in methods for cardiovascular research are advantageous (cardiomyocytes isolation and culture, in vitro contractility analysis, small animal models for cardiovascular diseases, echocardiography)
Excellent knowledge of English (written and oral), basic knowledge of German
Strong analytical thinking, ability to work in a team, good self-organization and sense of responsibility
Goal-oriented, individual training and development opportunities, excellent mentoring
Working with the latest techniques / technical equipment
Flexible working hours within the framework of flexitime
Possibility of doctorate
Regular team meetings
A highly innovative research project with clinical relevance
Access to state-of-the-art facilities and analysis possibilities from integrative physiology to mass spectroscopy
Collectively agreed remuneration, attractive company pension scheme (VBL)
30 days vacation
Sustainable travel: job ticket
Family-friendly working environment: cooperative arrangements for childcare, subsidy for child vacation care, advice for employees with relatives in need of care
Wide range of health, prevention and sports offers