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.

全球约 1/4 的人口患有寄生虫感染。我们的研究重点是感染超过 2 亿人的血吸虫寄生虫，其中 90% 生活在撒哈拉以南非洲地区。单个血吸虫可以在感染者体内存活多年，这反映了寄生虫干扰宿主免疫反应的能力[1]。虽然这可能会促进感染的慢性化，但它也会导致对旁观者挑战（包括联合感染和疫苗）的免疫抑制。为了实现这一目标，寄生虫会产生多种干扰宿主免疫力的抑制分子。然而，这些分子在血吸虫感染中的身份以及它们调节宿主免疫的机制尚不清楚。在本项目中，您将研究血吸虫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抑制免疫反应。由于免疫反应受损与慢性感染（即存在产卵成虫的情况下）密切相关，因此您将检验成虫和/或虫卵产生调节免疫细胞激活和疫苗反应的免疫抑制蛋白的假设。为此，您将首先识别蠕虫和卵分泌的蛋白质，并利用哺乳动物细胞中的高通量重组表达方法 [2]，然后使用体外和体内免疫学测定来测试这些分子的影响。这将重点关注对模型抗原和人类疫苗卡介苗的免疫反应。更好地了解血吸虫建立慢性感染的分子机制可以带来新的抗寄生虫策略，以及发现控制过敏和自身免疫性疾病的新候选治疗药物。您将在约克接受两名 MRC 的监督资助研究人员采取补充方法来研究血吸虫免疫抑制（宿主免疫途径和假定的寄生虫免疫调节分子）。该项目通过与 NIBSC（英国国家生物标准与控制研究所）的第三位主管的合作而受益匪浅，这位主管是卡介苗疫苗和结核病小鼠模型方面的专家。该项目将为您提供多种生化技术和体外/体内免疫学方面的广泛培训。该项目适合生物医学科学、生物化学、生物学或对免疫学和/或寄生虫学有浓厚兴趣和背景知识的相关学科的毕业生。