在University of Bern(瑞士伯恩)的Melody Huang是一位麻醉科的group leader。她现在 在招收博士生(2023年起100%薪水PhD student)。瑞士薪水非常优渥，环境舒适，生技产 业非常发达。对免疫、生化、神经科学有兴趣的学生可以考虑。以下是详细内容: ------------------------------------------------------------------------------ ---------------------------------- PhD in Anaesthesiology: Proposal for a PhD’s Thesis Project Title: Inflammatory regulation effect of microRNAs on the innate and adaptive immunit y under physiological and traumatic conditions Background: Anesthesia and surgery can result in a variety of metabolic and endocrine resp onses, including an immunosuppressive impact on patients during the immediate post-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 cla ss II (MHC-II) cell surface receptor found on antigen-presenting cells and pla ys a key role in initiating adaptive immune responses. In severely immunocompr omised patients with conditions like sepsis and severe cases of coronavirus di sease 2019 (COVID-19), the number of HLA-DR molecules expressed on leukocytes is considered to correlate with infectious complications and patients’ probab ility of survival. Neutrophil Extracellular Trap (NET) formation, NETosis, is a relatively newly identified function of neutrophils. Although NETosis is shown to involve in va rious immune processes including the pathogenesis of sepsis, until today NETs formation during an immunosuppressed state such as in perioperative surgical t rauma remains largely unclear. It is conceivable that NETosis may be compromis ed during an immunodeficiency state. Aim: The aim of this PhD thesis project is to investigate if the above-described pe rioperative immunosuppression could be reflected in the reduction of monocytic HLA-DR expression and the NETosis rate using in vitro, ex vivo, and in vivo m odels. Further, we will systematically examine the HLA-DR regulation by microR NAs, pro- or anti-inflammatory cytokines, hormones, and neurotransmitters. The overarching goal of this research project is to facilitate clinical anesth esiology and immunology studies by providing an efficient preclinical screenin g platform for candidate therapeutics, in compliance with the 3R (Replace, Red uce, 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, ELI SA) -RNA sequencing -Statistical analysis Potential Relevance: Until now genome-wide association studies have not yielded early sepsis biomar kers or targets for treatment. We expect to identify novel candidate miRNA reg ulators of monocytic surface HLA-DR expression. Further, the whole blood assay may provide a broader assessment of additional serum biomarker and/or biosign ature profiles. The outcome of this research will not only advance our knowled ge of the genetic regulatory network underlying HLA-DR expression alterations during an immunosuppressed state, such as in severe surgical trauma, but will also help reveal early biomarkers and ultimately potential novel treatment opt ions 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 Regul ating 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 experi mentation 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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