Pulmonary innate immunity and pathogens of the order Actinomycetales

候选人：特雷西·卡尔森博士是一名有执照的兽医，具有兽医解剖病理学的董事会资格，即将完成俄亥俄州立大学(OSU)的博士培训计划。K01 SERCA将支持她的训练和向科学独立的进步。环境：俄亥俄州立大学拥有广泛的生物医学研究综合体，包括位于医学院/兽医学院的最先进的核心设施。首席研究员的导师拉里·施莱辛格博士是传染病部门和微生物界面生物学中心的主任。施莱辛格博士是培训博士生和K奖学员的经验丰富的导师。培训计划：K奖的第一年将用于支持卡尔森博士在施莱辛格博士实验室的指导环境中完成博士培训。最后四年将被用来促进卡尔森博士按照研究提案中概述的计划向独立研究人员过渡。这将培养在竞争激烈的工作人员和教员科学家职位上的就业资格。研究：呼吸道病原体与先天免疫系统的最初相互作用对于决定疾病结局至关重要，特别是对于放线菌目的细菌，如分枝杆菌和红球菌，它们有能力生活在先天免疫细胞(肺泡巨噬细胞)中。在体外试验中，局部肺环境的相互作用，特别是表面活性蛋白D，对结核分枝杆菌具有抗菌作用。在这项研究方案中，我们将通过探索SP-D突变对感染结局的影响，进一步确定SP-D与结核分枝杆菌的相互作用，以及它在体外和体内对细菌存活的影响。其他研究将集中在肺部宿主对相关的马红球菌的反应，这种细菌是免疫功能低下(AIDS)患者机会性肺部疾病的重要来源，也是造成经济损失和幼马发病的重要原因。确定和调节肺环境与这些病原体的相互作用将为研究潜在的靶向免疫疗法开辟新的途径。 公共卫生相关性：结核病是由单一传染病病原体引起的主要死亡原因之一，感染了世界上约三分之一的人口。相关的马红球菌是艾滋病患者的一种机会性感染，也是马业经济损失/发病的原因。我们的项目将定义这些细菌与肺固有免疫系统的初步相互作用，并产生免疫治疗的新方法。

DESCRIPTION (provided by applicant): THE CANDIDATE: Dr. Tracy Carlson, a licensed veterinarian with board-eligibility in veterinary anatomic pathology, is completing a Ph.D. training program at the Ohio State University (OSU). The K01 SERCA will support her training and progression to scientific independence. THE ENVIRONMENT: OSU has an extensive biomedical research complex including state of the art core facilities in the Colleges of Medicine / Veterinary Medicine. Dr. Larry Schlesinger, the Principal Investigator's mentor, is the Director of both the Infectious Disease Division and the Center for Microbial Interface Biology. Dr. Schlesinger is an experienced mentor in the training of Ph.D. students and K award trainees. THE TRAINING PLAN: The first year of the K award will be used to support the completion of the Ph.D. training of Dr. Carlson in a mentored environment in Dr. Schlesinger's laboratory. The last four years will be used to facilitate Dr. Carlson's transition to an independent researcher following the plan outlined in the research proposal. This will foster eligibility for employment in competitive staff and faculty scientist positions. THE RESEARCH: The initial interaction of respiratory pathogens with the innate immune system is critical for determining the outcome of disease particularly for bacteria of the order Actinomycetales, such as Mycobacteria and Rhodococcus spp., which have the ability to live in innate immune cells (alveolar macrophages). Interaction of the local lung environment, in particular surfactant protein D, has antimicrobial effects on Mycobacterium tuberculosis in in vitro assays. In this research proposal we will further define the interaction of SP-D with M. tuberculosis and the effect it has on the survival of the bacteria in in vitro assays and in vivo in part by exploring the effect of SP-D mutations on the outcome of infection. Additional research will focus on the pulmonary host response to the related Rhodococcus equi, a bacterium that is a significant source of opportunistic pulmonary disease in immunocompromised (AIDS) patients as well as being an important cause of economic loss and morbidity as a disease of young horses. Defining and modulating the interaction of the pulmonary environment with these pathogens will open new avenues of investigation into potential targeted immunotherapies. PUBLIC HEALTH RELEVANCE: Tuberculosis is one of the leading causes of death due to a single infectious disease agent and infects ~ 1/3 of the world's population. The related Rhodococcus equi is an opportunistic infection in AIDS patients and a cause of economic loss / morbidity in the equine industry. Our project will define the initial interaction of these bacteria with the lung innate immune system and generate novel approaches to immunotherapy.