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Archiv-Übersicht     Angebot Nr. 12593

Angebotsdatum: 15. Dezember 2017
Art der Stelle: Doktorarbeit / Diplomarbeit
Fachgebiet: Biologie > Entwicklungsbiologie
Titel des Themas: PhD position in “establishment of non-centrosomal MTOCs”

Institut: Pathologie
Prof. Felix Engel
Schwabachanlage 12
91054 Erlangen
Tel.: 09131 85 25699   Fax.:
Bundesland: Bayern
Homepage: http://www.nephropathologie.uk-erlangen.de/en/ag-engel-exp-renal-and-cardiovascular-research/
E-Mail Kontakt: mail

Beschreibung: Background: Cardiovascular diseases, characterized in many cases by the irreversible loss of cardiomyocytes, are a major socio-economic burden predicted to further increase. A promising future therapy is to enhance the proliferation of postnatal cardiomyocytes which are mostly withdrawn from the cell cycle. However, the efficiency of identified pro-proliferative factors declines markedly with the age of cardiomyocytes, being very low for adult cardiomyocytes and thus, a human therapy for heart failure is still elusive. Recently, we have shown that the centrosomal microtubule organizing center (MTOC) undergoes a programmed disassembly in developing mammalian cardiomyocytes, most probably resulting from the recruitment of MTOC components to the nuclear envelope, as previously also observed in skeletal muscle. The disassembly is associated with a decline of cardiomyocyte proliferative capacity consistent with the requirement of the centrosome for mammalian cell cycle progression and suggesting that the relocalization of the MTOC contributes to the inability of cardiomyocytes to proliferate. This hypothesis is supported by our finding that adult zebrafish and newt cardiomyocytes, which retain proliferative capacity, do not disassemble their centrosomal MTOC. Our observation raises several questions such as: How does centrosome disassembly occur in mammalian cardiomyocytes? Is this process reversible? What is the purpose of a nuclear MTOC? Answering these long-standing questions is of relevance not only to cardiac regeneration but developmental, cellular, and cancer biology as well.

Project: The selected PhD candidate will work on a recently funded DFG project entitled “Establishment and function of non-centrosomal MTOCs in striated muscle”. She/he will be part of a team that is completed by another PhD candidate as well as a senior postdoc. The overall goal of the funded project is the detailed characterization of MTOC proteins during non-centrosomal MTOC formation, elucidation of mechanisms that control non-centrosomal MTOC formation, and the functional characterization of MTOC relocalization to the nuclear envelope.

About Prof. Engel: He has been trained at the Max Delbrück Center for Molecular Medicine (Berlin) and the Harvard Medical School. Subsequently, he received the Sofja Kovalevskaja Award and held faculty positions at the Harvard Medical School and the Max Planck Institute for Heart and Lung Research. Currently, he is professor at the Friedrich-Alexander-Universität Erlangen-Nürnberg. His lab has published in journals such as PNAS, eLife, Development, Advanced Functional Materials, and Biomaterials. In addition, his lab contributed to publications in journals such as Cell and Developmental Cell.
Methoden: Methodology: It is planned to utilize among others C2C12, hiPSC, and primary myoblast and cardiomyocyte cell culture, immunofluorescence staining, Co-immunoprecipitation, cloning, live cell imaging, transcriptomics and proteomics, bioinformatics, cell fusion, FACS, siRNA and CRISPR/Cas9 technology, biomechanical assays, and the zebrafish as in vivo model.
Anfangsdatum: 1. April 2018
Geschätzte Dauer: 3 years
Bezahlung: TVL13 (65%)
Papers: Zebrowski et al., eLife 2015