[情報] 瑞士伯恩大學(Bern)徵麻醉科phd學生

在University of Bern(瑞士伯恩)的Melody Huang是一位麻醉科的group leader。她現在在招收博士生(2023年起100%薪水PhD student)。瑞士薪水非常優渥，環境舒適，生技產業非常發達。對免疫、生化、神經科學有興趣的學生可以考慮。以下是詳細內容:

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PhD in Anaesthesiology: Proposal for a PhD’s Thesis Project

Title:
Inflammatory regulation effect of microRNAs on the innate and adaptive immunity under physiological and traumatic conditions

Background:
Anesthesia and surgery can result in a variety of metabolic and endocrine responses, including an immunosuppressive impact on patients during the immediatepost-operative period, which may further implicate in the development of post-operative septic complications and tumor metastasis formation.
Human leukocyte antigen–DR isotype (HLA-DR) is a major histocompatibility class II (MHC-II) cell surface receptor found on antigen-presenting cells and plays a key role in initiating adaptive immune responses. In severely immunocompromised patients with conditions like sepsis and severe cases of coronavirus disease 2019 (COVID-19), the number of HLA-DR molecules expressed on leukocytesis considered to correlate with infectious complications and patients’ probability of survival.
Neutrophil Extracellular Trap (NET) formation, NETosis, is a relatively newlyidentified function of neutrophils. Although NETosis is shown to involve in various immune processes including the pathogenesis of sepsis, until today NETsformation during an immunosuppressed state such as in perioperative surgical trauma remains largely unclear. It is conceivable that NETosis may be compromised during an immunodeficiency state.

Aim:
The aim of this PhD thesis project is to investigate if the above-described perioperative immunosuppression could be reflected in the reduction of monocytic HLA-DR expression and the NETosis rate using in vitro, ex vivo, and in vivo models. Further, we will systematically examine the HLA-DR regulation by microRNAs, pro- or anti-inflammatory cytokines, hormones, and neurotransmitters.
The overarching goal of this research project is to facilitate clinical anesthesiology and immunology studies by providing an efficient preclinical screening platform for candidate therapeutics, in compliance with the 3R (Replace, Reduce, Refine) concepts.

Research work, methods:
Research work and main methods may cover:
-Cell culture, whole blood culture, animal models
-RNAi assays (e.g., miRNA transfection)
-Flow cytometry
-Fluorescent live imaging
-Morphology and histopathology
-Various staining techniques (e.g., IHC, ISH, FISH)
-Various gene/protein expression quantification (e.g., qPCR, western blot, ELISA)
-RNA sequencing
-Statistical analysis

Potential Relevance:
Until now genome-wide association studies have not yielded early sepsis biomarkers or targets for treatment. We expect to identify novel candidate miRNA regulators of monocytic surface HLA-DR expression. Further, the whole blood assay may provide a broader assessment of additional serum biomarker and/or biosignature profiles. The outcome of this research will not only advance our knowledge of the genetic regulatory network underlying HLA-DR expression alterationsduring an immunosuppressed state, such as in severe surgical trauma, but willalso help reveal early biomarkers and ultimately potential novel treatment options for critically ill patients with severe sepsis and septic shock.

References:
1) Houseman M, Huang MY, Huber M, Staiger M, Zhang L, Hoffmann A, Lippuner C,St晈er F. Flow Cytometry-Based High-Throughput RNAi Screening for miRNAs Regulating MHC Class II HLA-DR Surface Expression. Eur J Immunol. 2022 May 25. doi: 10.1002/eji.202149735.
2) Paul, P. et al. A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation. Cell 145, 268-283, doi:10.1016/j.cell.2011.03.023 (2011).
3) Papayannopoulos, V., Neutrophil extracellular traps in immunity and disease. Nat Rev Immunol, 2018. 18(2): p. 134-147.

Requirements:
Team player; strong motivation to conduct research; creativity and independent thinking to generate new ideas; good knowledge in molecular and cell biology; knowledge of neurobiology and immunology and/or experience with animal experimentation would be a plus.

Contact details of supervisor:
Melody Ying-Yu Hedinger, [email protected], +41 31 632 08 26
Department for BioMedical Research
University Bern
Murtenstrasse 35, CH-3008 Bern

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