The heart is the first organ to form and function in the mammalian embryo. To generate a fully functional heart, complex processes that involve specification and determination of cardiac progenitor cells, the migration of this cell population to the organ-forming region, the differentiation of the precursor cells to specialized cell types, interaction and signaling within and between tissues, elaborate morphogenetic events and remodeling to form the proper shape of the heart, and finally organ growth and functional maturation have to be orchestrated. Even minor alterations in these events often result in serious cardiac malformations. Although detailed anatomic analysis of the developing heart has already been available for a long time, the molecular and cellular mechanisms that regulate cardiogenesis are still largely unknown. The identification and characterization of the genetic and molecular underpinnings of heart development is of critical interest since the wide spectrum of congenital cardiovascular malformations found from the prenatal period into adulthood has challenged clinicians and scientists for decades.

Therefore, the main objective of our workgroup "Molecular Cardiology" is to describe by in vitro (cell cultures) and in vivo (zebrafish and mouse) functional genomics approaches the genetic, molecular and cellular events leading to the specification and determination of cardiac precursor cells, their differentiation into specialized cardiac cell types, cardiac growth, maturation and function as well as the regeneration of the heart. The long-term goal of our research is to decipher the complex genetic and molecular networks of heart development and function and to use this information for the development of novel therapeutic treatment options for inherited and acquired heart diseases.

Profilbild von Prof. Dr. rer. nat. Steffen Just

Prof. Dr. rer. nat. Steffen Just

Head of Workgroup

Research

Nexilin, is a cardiomyopathy-associated F-actin binding protein, which is expressed specifically in human heart and skeletal muscle. Located at the Z-disks of sarcomeric units, it has an essential role in the maintenance of Z-disks and sarcomere integrity. Identified functions of Nexilin are to protect and stabilize Z-disks from forces generated within muscle contraction. Dilated cardiomyopathy-causing gene variants of Nexilin seem to lose the attachment ability to the sarcomeric scaffolding complex and hence Z-disk alignments become disrupted. To understand the molecular composition of cardiac Z-disks regarding how Nexilin is integrated, we are searching for new protein binding partners.Besides the structural character, Nexilin is also analyzed for its potential functional impact in biochemical signalling, mechanosensation and mechanotransduction.

The development of the vertebrate heart is not only dependent on molecular specifications and morphogenetic movements but also on organ growth. Cardiac growth can be accomplished by either hyperplasia or hypertrophy. Early in embryonic heart development cardiac growth is mainly due to hyperplasic cardiomyocyte proliferation hereby increasing cardiac cell mass. Thereafter the heart enlarges for the most part by hypertrophic expansion of the cardiomyocyte cell volume. The analysis of zebrafish mutants with defects in heart growth can help sheding light onto the molecular mechanisms beneath hyperplasic and hypertrophic processes.

In humans, cardiac infarction leads to myocardial cell death and scar formation, which subsequently lead to heart insufficiency. The zebrafish however has the capability to regenerate the heart completely after myocardial damage. Therefore we aim to understand the molecular pathways orchestrating myocardial regeneration and proliferation in zebrafish to develop therapeutic treatment strategies.

In search for molecules that control cardiac contractility, we isolated the zebrafish mutant main squeeze (msq), which displays progressive heart failure due to a mutation (msqL308P) within the Integrin-linked kinase (ILK) gene. It has been shown that the ILK-Pinch-Parvin (IPP) complex is crucial for mechanotransduction in cardiomyocytes by controlling the expression of the stretch responsive genes anf and vegf via PKB signaling (Bendig et al. 2006). For a better understanding of mechanotransduction in cardiomyocytes it is essential to learn more about the underlying molecular mechanisms. Therefore we investigate known interactors of ILK, by morpholino antisense oligonucleotide mediated gene knockdown in zebrafish.

Another aim is to identify new compounds which are able to reconstitute the cardiac function in msq mutants. In cooperation with the Karlsruher Institute of technology (K.I.T), we developed a high-troughput, fully-automated bioanalytics screening platform (Spomer et al., 2012). This robotics-assisted multicamera microscope allows us to easily screen the therapeutic relevance of small compound libraries on our zebrafish mutants in 96- or 384 well formats.

By a forward genetics approach in zebrafish, we recently isolated the mutant line schneckentempo (ste) and were able to demonstrate the essential role of regular mitochondrial function for the development and function of the heart. By positional cloning, we identified a mutation in the zebrafish dihydrolipoamidsuccinyltransferase (DLST) gene to cause the ste phenotype. DLST is part of the α-ketoglutarate dehydrogenase complex of the citric acid cycle in mitochondria, which are involved in energy production and provide ATP.

Myofibrillar myopathies (MFM) are progressive diseases of human heart and skeletal muscle. They are often associated with premature death. The muscle pathology is characterized by desmin-positve protein aggregates and myofibrillar degeneration. Half of all MFM are caused by mutations in genes encoding sarcomeric and extra-sarcomeric proteins (desmin, filamin C, plectin, VCP, FHL1, ZASP, myotilin, and αB-crystallin). Other half of these diseases are due to so far unidentified gene defects. The onset of the progressive muscle symptoms varies depending on the affected gene. FHL1- and plectin-related MFM may manifest either in childhood, adolescence or adulthood. Desmin- and αB-crystallin-related MFM tend to manifest in early and middle adulthood. Whereas disease onset beyond the forth decade of life is typical for myotilin-, ZASP-, VCP and filamin C-gene mutations. Also the clinical value is variable in MFM. Skeletal muscle weakness in the lower extremities is the most frequent initial clinical symptom. Additionally certain patterns of extra skeletal muscle involvement are typical for subtypes of MFM. Cardiac pathology is a characteristic hallmark of MFM due to desmin, αB-crystallin, FHL1 gene mutations. To date, no causative or even ameliorating therapies exist for these numerically significant group of hereditary myopathies. Since the molecular pathomechanism are largely unknown, a good model organism is essential for the identification and further analysis of the suitable illness genes. The obtained findings can later serve as a basis for the development of new therapies.

Some hereditary diseases are fatal for the patients but they are still not completely clarified. One of those is Epidermolysis bullosa simplex with muscular dystrophy (MD-EBS). It is characterized by severe skin blistering associated with muscular involvement and caused by defects in the plectin gene. Plectin is expressed in nearly all mammalian cells and acts as cytoskeletal crosslinker between microfilaments, microtubules and intermediate filaments.

With the aid of transgenic fish lines and knockdowns via morpholino injections, we are trying to characterize Plectin and its isoforms to achieve a better understanding of plectin and related diseases.

By positional cloning we identified a nonsense mutation within the SET- and MYND-domain containing protein 1 gene (smyd1) to be responsible for the flatline phenotype which shows disturbed sarcomere assembly restricted to fast-twitch skeletal muscle and heart muscle leading to loss of contraction. The methyltransferase Smyd1 localizes to the M-line, where it associates with myosin, and the nucleus, where it regulates gene expression. By rescue experiments several human mutation variants were tested because of their relevance of possibly leading to dilatative cardiomyopathies in humans.

Team

Profilbild von Prof. Dr. rer. nat. Steffen Just

Prof. Dr. rer. nat. Steffen Just

Head of Workgroup

 

 

Profilbild von Sylvia Dahme-Johanning

Sylvia Dahme-Johanning

Project Assistant

Profilbild von Dr. rer. nat. Isabelle Schneider

Dr. rer. nat. Isabelle Schneider

Postdoc

Profilbild von OA Dr. med. Mirjam Keßler

OA Dr. med. Mirjam Keßler

Profilbild von Dr. med. Karolina Weinmann

Dr. med. Karolina Weinmann

Profilbild von Manuel Rattka

Manuel Rattka

Profilbild von Dr. med. Alexander Pott

Dr. med. Alexander Pott

Profilbild von Federica Diofano

Federica Diofano

PhD Student

Profilbild von Deung-Dae Park

Deung-Dae Park

PhD Student

Profilbild von Karin Strele

Karin Strele

MTLA

Profilbild von Regine Baur

Regine Baur

MTLA

Profilbild von Katrin Vogt

Katrin Vogt

MTLA

Profilbild von Sabrina Diebold

Sabrina Diebold

MTLA

Profilbild von Renate Durst

Renate Durst

MTLA

Dr. Christoph Paone

Diana Krattenmacher

Dr. Anja Bühler

Dr. Maryam Shahid

Dr. Monika Kustermann, geb. Forster

Dr. Linda Raphel

Dr. Julia Segert

Dr. Steven Rudeck

Dr. Sofia Hirth

Dr. Muzamil Khan

Dr. John Bührdel

Dr. Daniela Asam

Dr. Linda Manta, geb. Gärtner

Dr. Eva Patzel

Dr. Ina Berger

Technicians

Hedwig Frank

Kristin Haugg

Publications

Lausser L*, Siegle L*, Rottbauer W, Frank D**,  Just S**, Kestler HA**.  Semantic Multi-Classifier Systems Identify Predictive Processes in Heart Failure Models across Species *equal contribution, **joint senior authors, Biomolecules 2018, 8(4), 158; doi.org/10.3390/biom8040158

Pott A, Just S. Metabolic Profiling of Glucocorticoid Deficiency: A "Fishing" Expedition. EBioMedicine. 2018 Oct 31. pii: S2352-3964(18)30476-6. doi: 10.1016/j.ebiom.2018.10.058. [Epub ahead of print]

Krämer LM, Brettschneider J, Lennerz JK, Walcher D, Fang L, Rosenbohm A, Balakrishnan K, Benckendorff J, Möller P, Just S, Willem M, Ludolph AC, Thal DR. Amyloid precursor protein-fragments-containing inclusions in cardiomyocytes with basophilic degeneration and its association with cerebral amyloid angiopathy and myocardial fibrosis. Sci Rep. 2018 Nov 9;8(1):16594. doi: 10.1038/s41598-018-34808-7.

Pott A*, Shahid M*, Köhler D, Pylatiuk C, Weinmann K, Just S** and Rottbauer W** Therapeutic Chemical Screen Identifies Phosphatase Inhibitors to Reconstitute PKB Phosphorylation and Cardiac Contractility in ILK-Deficient Zebrafish. *equal contribution, **joint senior authors, Biomolecules 2018, 8(4), 153; doi:10.3390/biom8040153

Krämer LM, Brettschneider J, Lennerz JK, Walcher D, Fang L, Rosenbohm A, Balakrishnan K, Benckendorff J, Möller P, Just S, Willem M, Ludolph AC, Thal DR. Amyloid precursor protein-fragments-containing inclusions in cardiomyocytes with basophilic degeneration and its association with cerebral amyloid angiopathy and myocardial fibrosis. Sci Rep. 2018 Nov 9;8(1):16594. doi: 10.1038/s41598-018-34808-7.

Pott A, Just S. Metabolic Profiling of Glucocorticoid Deficiency: A "Fishing" Expedition. EBioMedicine. 2018 Oct 31. pii: S2352-3964(18)30476-6. doi: 10.1016/j.ebiom.2018.10.058. [Epub ahead of print]

Segert J, Schneider I, Berger IM, Rottbauer W, Just S. Mediator complex subunit Med12 regulates cardiac jelly development and AV valve formation in zebrafish. Prog Biophys Mol Biol. 2018 Jul 20. pii: S0079-6107(18)30023-3. doi: 10.1016/j.pbiomolbio.2018.07.010. [Epub ahead of print]

Kustermann M, Manta L, Paone C, Kustermann J, Lausser L, Wiesner C, Eichinger L, Clemen CS, Schröder R, Kestler HA, Sandri M, Rottbauer W, Just S. Loss of the novel Vcp (valosin containing protein) interactor Washc4 interferes with autophagy-mediated proteostasis in striated muscle and leads to myopathy in vivo. Autophagy. 2018;14(11):1911-1927. doi: 10.1080/15548627.2018.1491491. Epub 2018 Aug 16.

Helferich AM, Brockmann SJ, Reinders J, Deshpande D, Holzmann K, Brenner D, Andersen PM, Petri S, Thal DR, Michaelis J, Otto M, Just S, Ludolph AC, Danzer KM, Freischmidt A, Weishaupt JH. Dysregulation of a novel miR-1825/TBCB/TUBA4A pathway in sporadic and familial ALS. Cell Mol Life Sci. 2018 Dec;75(23):4301-4319. doi: 10.1007/s00018-018-2873-1. Epub 2018 Jul 20.

Kramer F, Just S, Zeller T. New Perspectives: Systems medicine in cardiovascular disease. BMC Systems Biology ; 2018 Apr 25. doi:  10.1186/s12918-018-0579-5

Paone C, Diofano F, Park DD, Rottbauer W, Just S. Genetics of Cardiovascular Disease: Fishing for Causality. Frontiers in Cardiovascular Medicine. Front. Cardiovasc. Med., 01 June 2018, doi.org/10.3389/fcvm.2018.00060

Pott A, Bock S, Berger IM, Frese K, Dahme T, Keßler M, Rinné S, Decher N, Just S*, Rottbauer W*. Mutation of the Na+/K+-ATPase Atp1a1a.1 causes QT interval prolongation and bradycardia in zebrafish. * equal contribution. J Mol Cell Cardiol. 2018 Jul;120:42-52. doi: 10.1016/j.yjmcc.2018.05.005. Epub 2018 May 8.

Keßler M, Kieltsch A, Kayvanpour E, Katus HA, Schoser B, Schessl J, Just S*, Rottbauer W* (2018) A zebrafish model for FHL1-opathy reveals loss-of-function effects of human FHL1 mutations. * equal contribution. Neuromuscular Disorders doi:10.1016/j.nmd.2018.03.001

Silbernagel N, Walecki M, Schäfer MK, Kessler M, Zobeiri M, Rinné S, Kiper AK, Komadowski MA, Vowinkel KS, Wemhöner K, Fortmüller L, Schewe M, Dolga AM, Scekic-Zahirovic J, Matschke LA, Culmsee C, Baukrowitz T, Monassier L, Ullrich ND, Dupuis L, Just S, Budde T, Fabritz L & Decher N. The VAMP-associated protein VAPB is required for cardiac and neuronal pacemaker channel function. FASEB Journal. In press doi.org/10.1096/fj.201800246R

Brockmann SJ, Freischmidt A, Oeckl P, Muller K, Ponna SK, Helferich AM, Paone C, Reinders J, Kojer K, Orth M, Jokela M, Auranen M, Udd B, Hermann A, Danzer KM, Lichtner P, Walther P, Ludolph AC, Andersen PM, Otto M, Kursula P, Just S, Weishaupt JH (2018) CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease by haploinsufficiency. Hum Mol Genet doi:10.1093/hmg/ddx436

Paone C, Rudeck S, Etard C, Strahle U, Rottbauer W, Just S (2018) Loss of zebrafish Smyd1a interferes with myofibrillar integrity without triggering the misfolded myosin response. Biochem Biophys Res Commun doi:10.1016/j.bbrc.2018.01.060

Decher N, Ortiz-Bonnin B, Friedrich C, Schewe M, Kiper AK, Rinné S, Seemann G, Peyronnet R, Zumhagen S, Bustos D, Kockskämper J, Kohl P, Just S, González W, Baukrowitz T, Stallmeyer B, Schulze-Bahr E. Sodium permeable and "hypersensitive" TREK-1 channels cause ventricular tachycardia. EMBO Mol Med. 2017 Feb 27, doi: 10.15252/emmm.201606690

Straubinger J, Boldt K, Kuret A, Deng L, Krattenmacher D, Bork N, Desch M, Feil R, Feil S, Nemer M, Ueffing M, Ruth P, Just S, Lukowski R. Amplified pathogenic actions of angiotensin II in cysteine-rich LIM-only protein 4 negative mouse hearts. FASEB Journal. 2017 Jan 30, doi: 10.1096/fj.201601186

Just S, Raphel L, Berger IM, Bühler A, Keßler M, Rottbauer W. Tbx20 Is an Essential Regulator of Embryonic Heart Growth in Zebrafish. 2016 Dec 1, doi: 10.1371/journal.pone.0167306. eCollection 2016

Just S, Hirth S, Berger IM, Fishman MC, Rottbauer W. The mediator complex subunit Med10 regulates heart valve formation in zebrafish by controlling Tbx2b-mediated Has2 expression and cardiac jelly formation. Biochem Biophys Res Commun. 2016 Jun 22, doi:10.1016/j.bbrc.2016.06.088

Rudeck S, Etard C, Khan MM, Rottbauer W, Rudolf R, Strähle U, Just S. A compact unc45b-promoter drives muscle-specific expression in zebrafish and mouse. Genesis. 2016 Jun 13, doi: 10.1002/dvg.22953

Richter J, Rudeck S, Kretz AL, Kramer K, Just S, Henne-Bruns D, Hillenbrand A, Leithäuser F, Lemke J, Knippschild U. Decreased CK1δ expression predicts prolonged survival in colorectal cancer patients. Tumour Biol. 2016 Jan 7, doi: 10.1007/s13277-015-4745-8

Hirth S, Bühler A, Bührdel JB, Rudeck S, Dahme T, Rottbauer W, Just S. Paxillin and Focal Adhesion Kinase (FAK) Regulate Cardiac Contractility in the Zebrafish Heart. PLoS One. 2016 Mar 8, doi: 10.1371/journal.pone.0150323. eCollection 2016

Hoffmann S, Clauss S, Berger IM, Weiß B, Montalbano A, Röth R, Bucher M, Klier I, Wakili R, Seitz H, Schulze-Bahr E, Katus HA, Flachsbart F, Nebel A, Guenther SP, Bagaev E, Rottbauer W, Kääb S, Just S, Rappold GA. Coding and non-coding variants in the SHOX2 gene in patients with early-onset atrial fibrillation. Basic Res Cardiol. 2016 May, doi: 10.1007/s00395-016-0557-2

Bühler A, Kustermann M, Bummer T, Rottbauer W, Sandri M, Just S. Atrogin-1 Deficiency Leads to Myopathy and Heart Failure in Zebrafish. Int J Mol Sci. 2016 Jan 30, doi: 10.3390/ijms17020187

Aherrahrou Z, Schlossarek S, Stoelting S, Klinger M, Geertz B, Weinberger F, Kessler T, Aherrahrou R, Just S, Rottbauer R, Eschenhagen T, Schunkert H, Carrier L, Erdmann J. Knock-out of nexilin in mice leads to dilated cardiomyopathy and endomyocardial fibroelastosis. Basic Res Cardiol. 2016 Jan, doi: 10.1007/s00395-015-0522-5

Kessler M, Rottbauer W, Just S. Recent progress in the use of zebrafish for novel cardiac drug discovery. Expert opinion on drug discovery. 2015 Nov 2, doi: 10.1517/17460441.2015.1078788

Frese KS, Meder B, Keller A, Just S, Haas J, Vogel B, Fischer S, Backes C, Matzas M, Kohler D, Benes V, Katus HA, Rottbauer W. RNA splicing regulated by RBFOX1 is essential for cardiac function in zebrafish. Journal of cell science. 2015 Aug 15, doi: 10.1242/jcs.166850

Clemen CS, Marko M, Strucksberg KH, Behrens J, Wittig I, Gartner L, Winter L, Chevessier F, Matthias J, Turk M, Tangavelou K, Schutz J, Arhzaouy K, Klopffleisch K, Hanisch FG, Rottbauer W, Blumcke I, Just S, Eichinger L, Hofmann A, Schroder R. VCP and PSMF1: Antagonistic regulators of proteasome activity. Biochem Biophys Res Commun. 2015 Aug 7, doi: 10.1016/j.bbrc.2015.06.086

Zebrowski DC, Vergarajauregui S, Wu CC, Piatkowski T, Becker R, Leone M, Hirth S, Ricciardi F, Falk N, Giessl A, Just S, Braun T, Weidinger G, Engel FB. Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes. eLife. 2015 Aug 6, doi: 10.7554/eLife.05563

Buhrdel JB, Hirth S, Kessler M, Westphal S, Forster M, Manta L, Wiche G, Schoser B, Schessl J, Schroder R, Clemen CS, Eichinger L, Furst DO, van der Ven PF, Rottbauer W, Just S. In vivo characterization of human myofibrillar myopathy genes in zebrafish. Biochem Biophys Res Commun. 2015 May 29, doi: 10.1016/j.bbrc.2015.03.149

Hein K, Mittler G, Cizelsky W, Kuhl M, Ferrante F, Liefke R, Berger IM, Just S, Strang JE, Kestler HA, Oswald F and Borggrefe T. Site-specific methylation of Notch1 controls the amplitude and duration of the Notch1 response. Science signaling. 2015 Mar 24, doi: 10.1126/scisignal.2005892

Kessler M, Berger IM, Just S* and Rottbauer W*. Loss of dihydrolipoyl succinyltransferase (DLST) leads to reduced resting heart rate in the zebrafish. Basic Res Cardiol. 2015 Mar, doi: 10.1007/s00395-015-0468-7, * shared senior authorship

Clemen CS, Stockigt F, Strucksberg KH, Chevessier F, Winter L, Schutz J, Bauer R, Thorweihe JM, Wenzel D, Schlotzer-Schrehardt U, Rasche V, Krsmanovic P, Katus HA, Rottbauer W, Just S, Muller OJ, Friedrich O, Meyer R, Herrmann H, Schrickel JW, Schroder R. The toxic effect of R350P mutant desmin in striated muscle of man and mouse. Acta Neuropathol. 2015 Feb, doi: 10.1007/s00401-014-1363-2

Pott A, Rottbauer W, Just S. Functional genomics in zebrafish as a tool to identify novel antiarrhythmic targets. Current medicinal chemistry. 2014 Apr, 2014;21(11):1320-9. Review

Spomer W, Pfriem A, Alshut R, Just S, Pylatiuk C. High-throughput screening of zebrafish embryos using automated heart detection and imaging. Journal of laboratory automation. 2012 Dec, doi: 10.1177/2211068212464223

Just S, Berger IM, Meder B, Backs J, Keller A, Marquart S, Frese K, Patzel E, Rauch GJ, Katus HA, Rottbauer W. Protein kinase d2 controls cardiac valve formation in zebrafish by regulating histone deacetylase 5 activity. Circulation. 2011 Jul 19, doi: 10.1161/CIRCULATIONAHA.110.003301

Just S, Meder B, Berger IM, Etard C, Trano N, Patzel E, Hassel D, Marquart S, Dahme T, Vogel B, Fishman MC, Katus HA, Strahle U, Rottbauer W. The myosin-interacting protein smyd1 is essential for sarcomere organization. J Cell Sci. 2011 Oct 1, doi: 10.1242/jcs.084772

Hassel D* , Dahme T* , Erdmann J* , Meder B, Huge A, Stoll M, Just S, Hess A, Ehlermann P, Weichenhan D, Grimmler M, Liptau H, Hetzer R, Regitz-Zagrosek V, Fischer C, Nurnberg P, Schunkert H, Katus HA, Rottbauer W. Nexilin mutations destabilize cardiac z-disks and lead to dilated cardiomyopathy. Nat Med. 2009 Nov, doi: 10.1038/nm.2037 * Erstautoren

Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, Galuppo P, Just S, Rottbauer W, Frantz S, Castoldi M, Soutschek J, Koteliansky V, Rosenwald A, Basson MA, Licht JD, Pena JT, Rouhanifard SH, Muckenthaler MU, Tuschl T, Martin GR, Bauersachs J, Engelhardt S. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008 Dec 18, doi: 10.1038/nature07511

Rottbauer W*, Just S*, Wessels G, Trano N, Most P, Katus HA, Fishman MC. VEGF-PLC gamma1 pathway controls cardiac contractility in the embryonic heart. Genes Dev. 2005 Jul 1, doi: 10.1101/gad.1319405, * Erstautoren

Job Offers

The Molecular Cardiology lab (Head: Prof. Dr. Steffen Just) in the Department of Cardiology at the Ulm University Medical Center (Director: Prof. Dr. Wolfgang Rottbauer) is currently looking for

2 Postdoctoral Scientists (m/f) (2 years, extension possible) to study the molecular networks of heart development, function and regeneration.

We seek enthusiastic, highly motivated Researchers, who will join our research team working on the identification and characterization of genes and molecular networks that control heart development and regeneration, morphogenesis, growth and function in order to describe newtargets for therapeutic intervention. Techniques include in vitro (cardiomyocyte culture) and in vivo (mouse & zebrafish) functional genomics tools including advanced genetic techniques for gene editing (e.g. TALEN, CRISPR/Cas9, transgenesis), molecular biology, biochemistry, mouse and zebrafish genetics and advanced microscopic techniques. The successful candidates will particularly use already established knockout mouse strains and zebrafish models (mutants and transgenes) for functional analysis of signaling pathways during heart development, regeneration and function. The establishment of novel innovative and complementary models such as human iPS-derived cardiomyocytes, cardiac organoids or mouse models as well as the implementation of systems biology approaches is expected. The development of own research ideas and scientific projects is highly appreciated and will be supported.

We expect:

- a PhD degree in biology, biochemistry or molecular medicine

- a highly motivated, enthusiastic and efficient researcher

- experience in molecular and cellular biology

- knowledge of mouse physiology and experience with transgenic mice (beneficial)

- experience working with iPS cells (beneficial)

- excellent communication skills in spoken and written English

- a good publication record in peer-reviewed international journals

- capability of working in a team as well as independently

We offer:

- the opportunity to work in a dynamic and highly motivated team of biologists and physicians

- an interesting research project in a stimulating and competitive field of science

- payment according to the collective Agreement TV-L

- a workplace health promotion

- numerous training and continuing education opportunities

- support concerning the compatibility of job and family

Further information about our lab can be found at www.justlab.de

The positions are available from January 2019.

Applications including a CV, a short statement of your research experience and interests (max. 2 pages), and contact data for references should be emailed to Sylvia Dahme. Sylvia.Dahme@uniklinik-ulm.de

The Molecular Cardiology Lab (PI: Prof. Dr. Steffen Just) is currently offering positions for

1 Bachelor Thesis / 1 Master Thesis

to identify and characterize therapeutically active drugs by high-throughput small compound screening in Zebrafish.

The Zebrafish has emerged as a powerful model system for the rapid and straightforward in vivo analysis of small molecule bioactivity in numerous clinical indications including the identification and testing of novel therapeutic drugs. The Just Lab established within the European Network on Fish Biomedical Models (EUFishBioMed) in collaboration with the Institute for Applied Computer Science (IAI), Karlsruhe Institute of Technology (KIT), a high-throughput fully-automated, multicamera bioanalytics screening platform allowing for large-scale small-compound screening and in vivo cardiac phenotyping of zebrafish embryos. Additionally, we recently installed the BMBF-funded "Imaging machine" (Acquifer) for easy, precise, robust and smart high content screening. Thus, we are now looking for enthusiastic and highly motivated Students performing their Bachelor / Master Thesis on this interesting and relevant topic.

We offer:

- the opportunity to work in a dynamic and highly motivated team of biologists and technicians

- interesteting research projects in a stimulating and competitive filed of science

- varied "molecular biology" methods and state-of-the-art techniques

- excellent supervision by PostDocs

Collaborators

Out of the Lab