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Archiv-Übersicht     Angebot Nr. 15032

Angebotsdatum: 1. Februar 2024
Art der Stelle: Doktorarbeit / Diplomarbeit
Fachgebiet: Humanmedizin > Innere Medizin
Titel des Themas: The Cellular Landscape Underlying the Heterogeneity of Macrophages in Adult Testes During Normal and Diseased Conditions

Institut: Institute of Anatomy and Cell Biology, Aulweg 123, 35398 Giessen
Frau Faiqa Hossain
Leihgesterner Weg 52
35392 Giessen
Tel.:    Fax.:
Bundesland: Hessen
Homepage: https://www.uni-giessen.de/karriere/stellenangebote/ausschreibungen/wissenschaftliche-mitarbeiter/157-11
E-Mail Kontakt: mail

Beschreibung: Macrophages are the dominant immune cell population in the adult testis: They are derived from fetal liver precursors or early neonatal monocytes, but are maintained throughout adulthood without replacement from the blood. Our preliminary single-cell RNA sequencing (scRNA-Seq) analyses of CD45+ leukocytes isolated from healthy murine testes revealed several heterogenous testicular macrophage (TM) populations with distinct phenotypes, functions, transcriptional profiles and localization. Such heterogeneity suggests that niche-specific factors induce distinct macrophage-differentiation programs that drive TM subset evolution. Interestingly, under conditions of inflammation or TM-depletion, macrophages derived from blood monocytes occupy the empty testicular niche and differentiate into TM, suggesting that the testicular microenvironment can determine the TM phenotype. Indeed, our scRNA-Seq analysis revealed a distinct subset of interstitial macrophage populations that express insulin-like growth factor-1 — a growth factor that promotes Leydig cell differentiation — and various immunoregulatory molecules that regulate wound and tissue healing. This population could, therefore, be required to resolve inflammation and promote Leydig cell development. Elucidating the microenvironmental interactions that regulate TM development provides a better basis to understand the biological processes driving conditions such as male infertility. As such, this proposal aims: 1) To spatially resolve the testicular niche and the microenvironmental factors that determine TM phenotypes; 2) to elucidate whether infiltrating monocytes replace resident TM under inflammatory conditions; and 3) to understand the role of interstitial macrophage subsets under normal conditions. We will leverage a multi-omics approach based on scRNA-Seq, spatial transcriptomics, and CODEX multiplexed imaging to interrogate cell type-specific, in vivo knockout TM systems. We will combine these assays with in vitro analyses and functional profiling of the testes during homeostasis and under inflammatory conditions. This will allow us to refine the role of niche-specific factors in determining TM phenotypes and hopefully in the future, design suitable interventions for patients with inflammation-driven infertility.
Methoden: As a member of our group, you will be part of a dynamic international work environment that leverages cutting-edge technology, providing you with the opportunity to participate in diverse and impactful research projects. You will have the chance to showcase your research findings at both national and international scientific conferences. Additionally, you will have access to a comprehensive qualification program for doctoral students offered by the International Giessen Graduate Center for the Life Sciences GGL (https://www.uni-giessen.de/fbz/zentren/ggl). This program includes scientific seminars, hands-on courses, guidance in presentation and writing techniques, and support in career planning.
Anfangsdatum: 1. März 2024
Geschätzte Dauer: 3 years
Bezahlung: 65% of E 13 Hessen Tarif part-time position
Sonstiges: • Possession of a Master's or equivalent degree in Biology, Biochemistry, Immunology, Biological Science, Medicine, or related fields.
• Demonstrated keen interest in immunology/macrophage biology, coupled with strong motivation for research lab work.
• Ability to independently learn, comprehend, think critically, and conduct experiments, showcasing proficiency in mastering advanced techniques in immunology and molecular/cell biology.
• Desirable experience in working with animals, preferably holding a FELASA B certificate.
• Priority given to candidates with prior experience in immunology and proficiency in basic immunological techniques such as flow cytometry and cell culture.
• Basic knowledge of R and Python is desirable.
• Excellent communication and writing skills in English.
• Exceptional motivation, commitment, and a high level of teamwork ability as personal attributes.