Host defense against Shigella flexneri

宿主对福氏志贺氏菌的防御

• 批准号: 10601092
• 负责人: Zannatun Noor
• 金额: $ 7.46万
• 依托单位: INTERNATIONAL CTR/DIARRHOEAL DIS RES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-27 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10601092
• 关键词: 2 year old; 5 year old; Actins; Acute; Address; Age; Animal Model; Annual Reports; Antimicrobial Resistance; Bacteria; Bacterial Antibiotic Resistance; Bangladesh; Biological; Biopsy; Cell physiology; Cells; Cellular Infiltration; Cessation of life; Child; Child Health; Ciprofloxacin; Collaborations; Colon; Communicable Diseases; Convalescence; Development; Diarrhea; Drug resistance; Dysentery; Environment; Epithelial Cells; Flow Cytometry; Foundations; Gene Expression; Genes; Goals; Histologic; Host Defense; Human; IL8 gene; Immune; Immune response; Immunology; In Vitro; Incidence; Infection; Inflammation; Inflammatory; Intervention; Invaded; K-Series Research Career Programs; Knowledge; Life; Link; Memory; Mentors; Multi-Drug Resistance; NF-kappa B; Oral; Outcome; Pathway Analysis; Pathway interactions; Patients; Pharmacotherapy; Phenotype; Phosphotransferases; Population; Predisposition; Prevention; Production; Program Development; Proteins; Reporting; Research; Research Personnel; Resistance; Role; Scientist; Serotyping; Severities; Shigella; Shigella Infections; Shigella flexneri; Signal Transduction; Site; Supervision; Technology; Testing; Therapeutic; Tissues; Training; Type III Secretion System Pathway; United States; Universities; Vaccines; Virginia; antimicrobial; azithromycin resistance; career; career development; cell motility; clinical investigation; cytokine; design; experience; genetic signature; immune cell infiltrate; innovation; intestinal epithelium; low and middle-income countries; low income country; molecular diagnostics; pathogen; resistant strain; response; success; targeted treatment; therapeutic target; trafficking; transcriptome; transcriptome sequencing

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.

项目摘要 我们的目的：了解宿主对S. flexneri感染的反应 疗法。 假设：宿主基因和细胞过程对于有效的定殖和传播至关重要。 人类结肠中的弹性。这些基因和细胞过程可以通过比较结肠活检来发现 急性志刚性病到康复。 显着性：低收入国家每年报告约1.65亿例志菌病病例， 其中至少有100万例导致死亡，尤其是在五岁以下的儿童中（5）。非常 最近，志贺氏菌在整个病原体中排名最高，在 生命的第二年（10）。众所周知，疾病预防控制中心（CDC 威胁（18）。目前，尚无有效的疫苗，能够对许多人进行适当的保护 已经开发了不同的志贺氏菌血清型。 调查人员：Zannatun Noor博士是孟加拉国的早期职业研究科学家，并寻求 指导的研究职业发展奖。她将在孟加拉国的监督下进行研究 ICDDR的Rashidul Haque博士的导师，B和美国的导师William A. Petri博士在弗吉尼亚大学。两个都 导师正在协作工作超过二十年，并成功完成了不同的 研究。 创新：确定基因表达和细胞浸润以鉴定宿主免疫反应是 志智性突破性。我们将进行结肠活检的RNASEQ和CYTOF来确定宿主基因 表达和细胞浸润。 方法：为了检验我们的假设，我们的具体目的是-1）系统确定并表征结肠 基因表达谱响应于屈曲链球菌感染。 2）确定浸润免疫的身份 屈链球菌感染期间结肠中的细胞与康复。 环境：这项研究成功的关键是经验丰富的导师和高度积极进取的候选人 寻求必要的培训，实践经验和知识，以成为领先的独立 研究人员实施儿童健康干预措施，以减少低和 中等收入国家。导师是完全专业知识，例如在弗吉尼亚大学的我们的心理 ICDDR的免疫学和先前的技术和LMIC心理，b在临床研究中。两个主机 LMIC和美国研究所的研究所对候选人及其拟议职业有坚定的承诺 发展。