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资深初级研究员，但现在寻求向生物医学应用领域过渡。PI对这一领域的兴趣来自于对环境系统中生物运输过程的初步研究，这导致人们认识到物理运输对病原微生物的传播和生存的基本影响很少。在基于生物膜的感染中，低转运微环境的存在预计将保护病原体免受诸如抗微生物剂的危害。预计类似的过程也会介导病原体在环境系统中的存活，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，使他能够解决微生物学和生物医学中的基本问题，同时也提高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。培训阶段将涉及课程作业，临床经验，并在生物膜研究方法的指导。合作研究将集中在生物膜内运输限制微环境的发展，以及这些过程在介导代表性病原微生物铜绿假单胞菌和L.生物膜中的嗜肺菌。实验室实验将用于直接观察生物膜中的传输速率，确定在不同传输条件下暴露于抗微生物剂时病原体的存活情况，并评估生物膜低传输区域中病原体抗生素耐药性的发展。定量分析（建模）将被用来评估介导生物膜过程中的物理传输的基本作用，并改善水传播疾病传播的风险分析。

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.