MRes in Medical Mycology and Fungal Immunology

医学真菌学和真菌免疫学硕士

• 批准号: 2302801
• 金额: --
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2302801
• 关键词: MRes; Medical; Mycology; Fungal; Immunology

MRes project 1Investigating fungal cell wall dynamics using specific cell surface targeting antibodiesFungal infection is a notable global health issue. It contributes to 1.6 million deaths annually. Immunocompromised individuals are at increased risk. However, currently available antifungal therapy and diagnostic assays are inadequate. This leads to the urgent need of better antifungal agents and fungal diagnostic tests. UTR2 is a cell wall protein that contributes to Candida albicans virulence in murine model of disseminated candidiasis. Hence, phage display technique has been exploited to screen for potential high UTR2 binder. Here, we found that 1-D2 single chain antibody fragment (scAb) was the best binder among 188 clones. It demonstrated binding in UTR2 peptide and C.albicans whole cell enzyme-linked immunosorbent assay (ELISA). It also showed positive staining of hyphae in immunofluorescence staining. However, there was no growth inhibition effect in minimum inhibitory concentration (MIC) test. Further studies are required to further characterization of 1-D2. MRes project 2 The role of PTP1B in regulating fungal killing mechanisms in neutrophilsCandida albicans (C. albicans) infection contributes to significant mortality and morbidity worldwide. Innate immune response plays an essential role in antifungal immunity. Neutrophils, in particular, are potent phagocytes against C. albicans. Protein tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed phosphotyrosine-specific phosphatase that co-operates with protein tyrosine kinases to maintain physiological homeostasis of various cellular signalling pathways. Dr Wilson's laboratory has observed that myeloid-specific PTP1B knockout mice infected with C. albicans had decreased survival rate compared to wild-type control mice. Hence, we assessed the role of PTP1B in regulating C. albicans killing mechanisms in neutrophils. This study showed that PTP1B inhibition had no effect on neutrophil phagocytosis of C. albicans. However, PTP1B inhibition reduced peak reactive oxygen species (ROS) production upon stimulation with serum-opsonised yeast cells and hyphae but not with unopsonised yeast cells. Besides, PTP1B inhibition did not affect total ROS production in 5 hours or neutrophil killing of C. albicans. This study might provide a preliminary evidence of PTP1B involvement in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated ROS production upon C. albicans infection.

MRes项目1利用特异性细胞表面靶向抗体研究真菌细胞壁动力学真菌感染是一个值得注意的全球性健康问题。它每年导致160万人死亡。免疫力低下的人面临的风险更大。然而，目前可用的抗真菌治疗和诊断测定还不够。这导致迫切需要更好的抗真菌药物和真菌诊断测试。UTR 2是一种细胞壁蛋白，在播散性念珠菌病小鼠模型中有助于白念珠菌的毒力。因此，噬菌体展示技术已被用于筛选潜在的高UTR 2结合剂。在188个克隆中，我们发现1-D2单链抗体片段（scAb）是最好的结合剂。在UTR 2肽和白色念珠菌全细胞酶联免疫吸附试验（ELISA）中证明了结合。免疫荧光染色显示菌丝阳性。而最低抑菌浓度（MIC）试验无生长抑制作用。需要进一步研究以进一步表征1-D2。PTP 1B在嗜中性白念珠菌（Candida albicans，C.白色念珠菌）感染在世界范围内导致显著的死亡率和发病率。天然免疫应答在抗真菌免疫中起重要作用。特别是中性粒细胞是抗C.白色念珠菌蛋白酪氨酸磷酸酶1B（Protein tyrosine phosphatase 1B，PTP 1B）是一种广泛表达的磷酸酪氨酸特异性磷酸酶，与蛋白酪氨酸激酶协同作用维持多种细胞信号传导途径的生理稳态。威尔逊博士的实验室观察到，骨髓特异性PTP 1B基因敲除小鼠感染C。与野生型对照小鼠相比，白色念珠菌的存活率降低。因此，我们评估了PTP 1B在调节C.白念珠菌在中性粒细胞中的杀伤机制。本研究表明，PTP 1B抑制对中性粒细胞吞噬C.白色念珠菌然而，PTP 1B抑制减少峰值活性氧（ROS）的生产后，刺激血清调理酵母细胞和菌丝，但不与unopsonised酵母细胞。此外，PTP 1B抑制不影响5小时内总ROS产生或C.白色念珠菌。本研究为PTP 1B参与NADPH氧化酶介导的C.白色念珠菌感染