Pathogen survival in transport-limited environments

描述（由申请人提供）：PI是环境流体力学和运输过程领域的一名成熟的初级研究员，但现在寻求将职业过渡到生物医学应用。PI对这一领域的兴趣源于环境系统中生物运输过程的初步工作，这导致人们认识到物理运输对致病微生物传播和生存的基本影响的研究很少。在基于生物膜的感染中，低转运微环境的存在有望保护病原体免受诸如抗微生物剂等危害。预计类似的过程也会介导病原体在环境系统中的生存，从而在水媒疾病的传播中发挥重要作用。PI提出了一个广泛的培训和研究计划，这将使他准备解决微生物学和生物医学的基本问题，同时也推进了物理运输环境在介导病原微生物的生长、传播和生存中的作用的基本知识。培训阶段将包括课程作业、临床经验和生物膜研究方法的指导。合作研究将集中在生物膜内运输受限微环境的发展，以及这些过程在介导生物膜中具有代表性的致病微生物铜绿假单胞菌和嗜肺乳杆菌的传播和存活中的作用。实验室实验将用于直接观察生物膜的运输速率，确定病原体在不同运输条件下暴露于抗微生物药物时的存活率，并评估居住在生物膜低运输区域的病原体的抗生素耐药性发展。定量分析（建模）将用于评估物理运输在介导生物膜过程中的基本作用，并改进对水媒疾病传播风险的分析。

DESCRIPTION (provided by applicant): The PI is a well-established junior investigator in the field of environmental fluid mechanics and transport processes, but now seeks to make a career transition to biomedical applications. The PI's interest in this field developed from preliminary work on biological transport processes in environmental systems, which led to the realization that there has been little study of the fundamental effects of physical transport on the transmission and survival of pathogenic microorgansims. In biofilm-based infections, the presence of low-transport microenvironments is expected to protect pathogens from hazards such as anti-microbial agents. Similar processes are also expected to mediate the survival of pathogens in environmental systems, and thus to play an important role in the transmission of water-borne disease. The PI proposes an extensive training and research program that will prepare him to address fundamental problems in microbiology and biomedicine while also advancing basic knowledge of the role of the physical transport environment in mediating the growth, transmission, and survival of pathogenic microorganisms. The training phase will involve coursework, clinical experience, and instruction in methods for biofilm research. Collaborative research will focus on the development of transport-limited microenvironments within biofilms and the role of these processes in mediating the transmission and survival of the representative pathogenic microorganisms P. aeruginosa and L. pneumophila in biofilms. Laboratory experiments will be used to directly observe transport rates in biofilms, determine pathogen survival when exposed to anti-microbial agents under different transport conditions, and assess the development of antibiotic resistance in pathogens residing in low-transport regions of biofilms. Quantitative analysis (modeling) will be used to assess the fundamental role of physical transport in mediating biofilm processes, and to improve analysis of the risk of water-borne disease transmission.