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Archiv-Übersicht     Angebot Nr. 13830

Angebotsdatum: 10. März 2020
Art der Stelle: Doktorarbeit
Fachgebiet: Biologie > Sonstiges
Titel des Themas: PhD position in immunology and stem cell research

Institut: Universitätsklinik Ulm, Innere Medizin I
Adresse:
Prof. Reinhold Schirmbeck
Albert Einstein Allee 23
89081 Ulm
Tel.: +49 (0)731-5004-4685   Fax.:
Bundesland: Baden-Württemberg
Homepage:
E-Mail Kontakt: mail

Beschreibung: Our groups at the University Hospital Ulm (Internal Medicine I; R. Schirmbeck) and the Ulm University (Institute of Molecular Medicine; H. Geiger) focus on basic research projects that explore the development of young and aged immune systems starting from hematopoietic stem cells and on translational approaches to rejuvenate aged hematopoietic stem cells with the aim to restore the functionality of an old immune system.

Background: Aging-associated remodeling of the immune system impairs its functional integrity and contributes to increased morbidity and mortality in the elderly. We previously showed that aging of hematopoietic stem cells (HSCs), from which all cells of the adaptive immune system ultimately originate, plays a crucial role in the remodeling of the aged immune system. Aging of HSCs is, in part, driven by elevated activity of the small RhoGTPase Cdc42 and that aged HSCs can be rejuvenated in vitro by inhibition of the elevated Cdc42 activity in aged HSCs with the pharmacological compound CASIN. Importantly, aged HSCs treated with CASIN reestablished an immune system similar to that of young animals, and thus capable of mounting a strong immune response to vaccination.
In ongoing studies, we will focus our analyses on
- transcriptional and epigenetic profiles of cell populations along the HSC to CD8+ T cell differentiation axis in recipients of young, old, and rejuvenated old HSCs
- qualitative, quantitative and functional differences among the newly reconstituted CD8+ T-cell systems in recipients of young, old, and rejuvenated old HSCs
- the type of reconstitution and function of HSC-derived T-cell subsets emerging in an aged environment (niche/thymus) of aged recipients



Methoden: Methods:
- Isolation and characterization of hematopoietic stem cells
- Adoptive transfer and immunization studies in mice
- Detection and characterization of murine immune cell populations by flow cytometry and RNA-Seq, ATAC-Seq analyses
- Generation and maintenance of mouse cohorts
Anfangsdatum: 1. Mai 2020
Geschätzte Dauer: 3 Jahre
Bezahlung: TV-L E13/65%
Papers: Literature:[1]Leins H, Mulaw M, Eiwen K, Sakk V, Liang Y, Denkinger M, et al. Aged murine hematopoietic stem cells drive aging-associated immune remodeling. Blood. 2018;132:565-76.
Sonstiges: Qualification:
- MSc degree in molecular medicine, biology, biochemistry or equivalent
- Interest in immunology (T cells) and stem cells
- Expertise in flow cytometric analyses; mouse Experiments

We offer excellent working conditions in an inter-disciplinary project (immunology and stem cell research), associated with the PhD program of the international graduate school of molecular medicine.

The application should contain a CV and (degree) certificates.

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