Investigating the molecular and cellular basis of impaired vaccine responses in parasitic worm infection

研究寄生虫感染中疫苗反应受损的分子和细胞基础

• 批准号: 2889711
• 金额: --
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2889711
• 关键词: Investigating; molecular; cellular; basis; impaired

Parasitic helminth infections afflict ~1/4 of the global population. Our studies have focused on schistosome parasites that infect >200 million people, 90% of whom live in sub-Saharan Africa. Individual schistosome worms can survive for many years within infected people, and this reflects the parasite's ability to interfere with host immune responses [1]. Whilst this likely evolved to promote infection chronicity, it also causes immune suppression to bystander challenges including co-infections and vaccines. To achieve this, parasitic worms produce a variety of inhibitory molecules that interfere with host immunity. However, the identity of these molecules in schistosome infection and the mechanisms by which they modulate host immunity are not well understood.In this project, you will investigate the molecular and cellular basis of schistosome-induced immune suppression, with a focus on vaccine-induced immune responses. As impaired immune responses are most strongly associated with chronic infection (i.e. in the presence of egg-laying adult worms), you will test the hypothesis that adult worms and/or eggs produce immunosuppressive proteins that modulate immune cell activation and vaccine responses. To do this, you will first identify worm and egg secreted proteins and utilise high-throughput methods of recombinant expression in mammalian cells [2], before testing the impact of these molecules using in vitro and in vivo immunological assays. This will focus on immune responses to both model antigens and following the human vaccine, BCG. Greater understanding of the molecular mechanisms by which schistosomes to establish chronic infection can lead to new anti-parasite strategies as well as the discovery of novel therapeutic candidates in the control of allergic and auto-immune conditions.You will be supervised in York by two MRC funded researchers who take complementary approaches to investigate schistosome immune suppression (host immunological pathways and putative parasite immunomodulatory molecules). The project benefits greatly through collaboration with a third supervisor based at NIBSC (National Institute of Biological Standards and Control, UK) who is an expert in mouse models of BCG vaccination and tuberculosis. Together, this project will provide you with extensive training in multiple biochemical techniques and in vitro/in vivo immunology. The project will be suitable for a graduate in Biomedical Sciences, Biochemistry, Biology or related subjects with a strong interest and background knowledge of immunology and/or parasitology.

寄生虫的蠕虫感染困扰着全球人口的〜1/4。我们的研究集中在感染> 2亿人的黑孢子寄生虫上，其中90％居住在撒哈拉以南非洲。个体的血吸虫蠕虫可以在受感染的人中生存多年，这反映了寄生虫干扰宿主免疫反应的能力[1]。尽管这可能促进感染的慢性，但它也会导致免疫抑制旁观者的挑战，包括共同感染和疫苗。为此，寄生虫产生各种干扰宿主免疫的抑制分子。然而，这些分子在黑素感染中的身份以及它们调节宿主免疫的机制尚不清楚。在该项目中，您将研究血块体诱导的免疫抑制的分子和细胞基础，重点是疫苗诱导的免疫反应。由于免疫反应受损与慢性感染最密切相关（即在存在卵子成年蠕虫的情况下），您将测试成年蠕虫和/或卵产生免疫抑制蛋白的假设，可调节免疫细胞激活和疫苗反应。为此，您将首先鉴定蠕虫和卵子分泌的蛋白质，并在使用体外和体内免疫学测定中测试这些分子的影响之前，先利用哺乳动物细胞中重组表达的高通量方法[2]。这将着重于对模型抗原的免疫反应和遵循人类疫苗BCG的免疫反应。对建立慢性感染的分子体的分子机制有更深入的了解，可以导致新的抗寄生虫策略以及发现新型治疗候选者，以控制过敏和自身免疫性状况。分子）。该项目通过与BCG疫苗接种和结核病老鼠模型专家的NIBSC（美国国家生物标准与控制学院）的第三位主管的合作受益匪浅。该项目将共同为您提供多种生化技术和体外/体内免疫学的广泛培训。该项目将适合于生物医学科学，生物化学，生物学或相关学科的毕业生，对免疫学和/或寄生虫学具有浓厚的兴趣和背景知识。