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Archiv-Übersicht     Angebot Nr. 14560

Angebotsdatum: 13. April 2022
Art der Stelle: Doktorarbeit
Fachgebiet: Biologie > Sonstiges
Titel des Themas: Governors of innate immunity responses after myocardial infarction: Identifying crucial healing mechanisms

Institut: Klinik für Kardiologie, Angiologie und Pneumologie
Prof. Florian Leuschner
Im Neuenheimer Feld 410
69120 Heidelberg
Tel.:    Fax.:
Bundesland: Baden-Württemberg
Homepage: http://https://www.umm.uni-heidelberg.de/grk2727/
E-Mail Kontakt: mail

Beschreibung: The healing process after myocardial infarction (MI) is characterized by a biphasic, tightly orchestrated myeloid cell response. While neutrophils and pro-inflammatory monocytes (Mo) dominate the first days after MI, reparative macrophages (Mac) ensure resolution of inflammation at later stages.
We hypothesize that other accumulating low abundant leukocyte sub-populations critically impact this switch from a pro- to an anti-inflammatory cardiac microenvironment. Single-cell RNA sequencing analyses from hearts after MI in mice led to the conclusion that basophils control Mo/Mac polarization in the infarcted heart via Interleukin (IL)-4 and IL-13.
We now aim to go deeper in describing and understanding these interrelationships: 1. How exactly does augmented basophil accumulation affect the innate immune response after MI and what is the impact of basophilia-inducing co-morbidities on MI healing? 2. Which alterations in the translatome of Mo/Mac can be observed in the presence and absence of basophils?
The PhD research project outlined here is well integrated in the framework of the DFG-funded RTG2727, offering various collaborative opportunities with neighboring research fields. These will e.g. elucidate the involvement of other accumulating leukocytes (such as NK/ILCs), explore novel mechanisms of cardiac Mac polarization and examine the impact of sepsis on resident cardiac Mac populations.
By advancing our understanding of healing mechanisms after MI, your research outcomes will make an important contribution to future efforts in ameliorating and preventing ischemic heart failure.
Methoden: In vivo models of cardiac injury, functional cardiac analyses, cell culture, next generation RNA-sequencing, Polysome profiling, Ribosome profiling, functional macrophage assays.
Anfangsdatum: 1. Juli 2022
Geschätzte Dauer: 3 Years
Bezahlung: E13 (65%)
Papers: Sicklinger F, Meyer IS, Li X, Radtke D, Dicks S, Zhang Y, Kuhn TC, Patel J, Boerries M, Schramm G, Frey N, Katus HA, Voehringer D, Leuschner F. Basophils balance healing after myocardial infarction via IL-4/IL-13. Journal of Clinical Investigation. 2021
Kuhn TC, Knobel J, Burkert-Rettenmaier S, Li X, Meyer IS, Jungmann A, Sicklinger F, Backs J, Lasitschka F, Müller OJ, Katus HA, Krijgsveld J, Leuschner F. Secretome analysis of cardiomyocytes identifies PCSK6 (Proprotein Convertase Subtilisin/Kexin Type 6) as a novel player in cardiac remodeling after myocardial infarction. Circulation. 2020
Leuschner F, Nahrendorf M. Novel functions of macrophages in the heart: insights into electrical conduction, stress, and diastolic dysfunction. European Heart Journal. 2020
Sonstiges: Cooperation partners
The project is part of the Research Training Group GRK2727 “InCheck” (Innate Immune Checkpoints in Cancer and Tissue Damage; www.umm.uni-heidelberg.de/grk2727/) that started on January 1, 2022 and is funded by the DFG (Deutsche Forschungsgemeinschaft). The projects are all embedded within the lively community of innate immunity in Heidelberg and Mannheim, and there will be interactions with collaboration partners in Vienna (University of Veterinary Medicine) and Stockholm (Karolinska Institutet).

Personal qualifications
You have so far built up a strong background in cell biology, molecular biology, biochemistry, bioinformatics or immunology and are eager to dedicate your scientific work to the field of immunology. You are highly motivated to learn and conduct research independently as well as to integrate yourself into a lively exchange within the RTG2727 community and profit from conferences, lab visits and courses. You hold a MSc degree in Biology, Biochemistry, Immunology or related subject and you have strong communication skills in English.