Host defense against Shigella flexneri

项目摘要 目的：了解宿主对S.福氏杆菌感染在发育中的潜在宿主定向 治疗学 假说：宿主基因和细胞过程是沙门氏菌高效定殖和传播的关键。 在人类结肠中的福氏杆菌。这些基因和细胞过程可以通过比较结肠活检发现 急性志贺氏菌病至恢复期。 重要性：低收入国家每年报告约1.65亿例志贺氏菌病， 其中至少有100万例导致死亡，特别是5岁以下的儿童（5）。非常 最近，志贺氏菌在总体病原体负担中排名最高， 生命的第二年（10）正如CDC所知，多重耐药志贺氏菌感染是一种“严重的”疾病。 威胁（18）目前，没有有效的疫苗能够提供足够的保护，以防止许多 志贺氏菌的不同血清型已经被开发出来。 研究人员：Zannatun Noor博士是来自孟加拉国的早期职业研究科学家， 研究职业发展奖。她将在孟加拉国的监督下进行这项研究 在icddr，B指导Rashidul Haque博士，在美国指导William A.弗吉尼亚大学的佩特里。两 导师们合作工作了二十多年，并成功地完成了不同的 问题研究 创新：确定基因表达和细胞浸润，以确定宿主的免疫反应是 志贺氏菌病的突破性进展我们将对结肠活检进行RNAseq和CyTOF，以确定宿主基因 表达和细胞浸润。 方法：为了验证我们的假设，我们的具体目标是：1）系统地确定和表征结肠炎 基因表达谱响应S.弗氏菌感染2)确定浸润性免疫细胞的身份 细胞在结肠S.福氏杆菌感染与恢复期。 环境：研究成功的关键是经验丰富的导师和积极主动的候选人， 寻求必要的培训，实践经验和知识，成为一个领先的独立 调查员在执行儿童保健干预措施，以减少传染病的负担， 中等收入国家。导师是互补的专业知识，如美国弗吉尼亚大学的导师， 免疫学和先进技术以及LMIC指导，临床研究B。东道国 LMIC的研究所和美国的研究所对候选人及其拟议的职业有很强的承诺 发展

Project Summary Our Objective: To understand the host response to S. flexneri infection in developing potential host directed therapeutics. Hypothesis: Host genes and cellular processes are essential for efficient colonization and dissemination of S. flexneri in the human colon. These genes and cell processes can be discovered by comparing colonic biopsies during acute shigellosis to convalescence. Significance: Approximately 165 million cases of shigellosis are annually reported in low-income countries, with at least 1 million of these cases resulting in death, especially in children under five years of age (5). Very recently, Shigella ranked the highest among the overall pathogen burden, with a particularly high incidence in the second year of life (10). As is well known to CDC, multidrug resistant Shigella infections are a “serious” threat (18). Currently, no effective vaccine with the ability to confer adequate protection against the many different serotypes of Shigella has been developed. Investigators: Dr. Zannatun Noor is an early career research scientist from Bangladesh and seeking a mentored research career development award. She will conduct the study under supervision of Bangladesh mentor Dr. Rashidul Haque at icddr, b and USA mentor Dr. William A. Petri at University of Virginia. Both mentors are working with collaboration for more than two decades and have successfully completed different studies. Innovation: Determine gene expression and cellular infiltration to identify the host immune response is ground-breaking in Shigellosis. We will conduct RNAseq and CyTOF of colon biopsies to determine host gene expression and cellular infiltration respectively. Approach: To test our hypothesis, our specific aims are- 1) Systematically determine and characterize colonic gene expression profiles in response to S. flexneri infection. 2) Determine the identity of infiltrating immune cells in the colon during S. flexneri infection vs convalescence. Environment: Key to success of the study are the experienced mentors and highly motivated candidate who is seeking for the necessary training, practical experience, and knowledge to become a leading independent investigator in implementing child health interventions to reduce burden of infectious diseases in Low and Middle-Income Countries. Mentors are complementary expertise, like US mentor at the University of Virginia in immunology and in advance technology and LMIC mentor at icddr, b in clinical investigation. Both the host institute at LMIC and US institute have strong commitment to the candidate and her proposed career development.