Investigating oral pathogen virulence within complex oral biofilm communities

描述(申请人提供)：居住在口腔中的复杂微生物群落现在被认为在宿主健康和疾病中发挥重要作用。在过去60年的研究中，口腔微生物生态学的主要焦点一直是单物种和双物种之间的相互作用。尽管一些研究包括多达10种细菌，但它们远远不能代表人类口腔中含有大约700种细菌的情况。早期的研究表明，营养因素，特别是碳水化合物摄入量和氮源，极大地影响口腔细菌的生长及其与健康/疾病的关系。然而，我们对群落层面上的这些相互作用的了解非常有限，目前还不清楚我们可以在多大程度上将仅对少数几个物种的研究成果转化为群落背景。这项建议试图通过解剖控制这些过程的转录和代谢物网络，了解细菌基因表达和信号分子如何协调健康和龋齿相关社区的发展。最终目标是了解低pH值下的关键代谢相互作用如何有助于口腔生物膜的生态和临床重要特性，例如选择致龋性。 细菌，健康相关社区的pH恢复，以及细胞与细胞之间的通讯。候选人埃德伦德博士对研究环境中细菌的生态功能有着长期的兴趣和历史，因此，口腔群落的生态学研究是她研究的合乎逻辑的延伸。在K99的指导阶段结束后，她的职业轨迹是成为一家领先的学术研究机构的助理教授，在那里她希望继续并深化她的口腔生物膜研究计划，履行教学职责，并培养未来的科学家。埃德伦德博士认为，从长远来看，一旦更多地了解口腔生物膜是如何被监管的，她的发现将为开发治疗和预防口腔疾病的新药提供重要信息。这项K99/R00建议旨在补充Edlund博士之前的研究经验，并为她提供实质性和必要的技术和智力专业知识，以及作为独立研究员发挥作用的信心。这位候选人将在加州大学洛杉矶分校接受K99培训，这将使她处于进入类似排名的大学的有利地位。Edlund博士选择的主要导师史博士和共同导师Dorrestein博士和McLean博士是经过精心挑选的，因为他们的相关、多样和互补的专业知识涵盖了她的提案的所有要素。此外，埃德伦德博士还组建了一个顾问委员会，由一群不同的基础科学家和内科医生组成，在她向独立研究员的转变过程中监督她的科学进步和职业发展。

DESCRIPTION (provided by applicant): The complex microbial communities that reside in the oral cavity are now accepted to play important roles in host health and disease. During the last 60 years of research the major focus of oral microbial ecology has been on single and dual species interactions. Even though a few studies include up to 10 species they are far from being representative of the human oral cavity that harbors approximately 700 bacterial species. Earlier studies show that nutritional factors especially carbohydrate intake and nitrogen sources greatly affect oral bacterial growth and their associations with health/disease. However, our understanding of these interactions at a community level is very limited and it is unclear to what extent we can translate the knowledge from studies of only a few species into a community context. This proposal seeks to understand how bacterial gene expression and signaling molecules orchestrate the development of both health and caries associated communities through dissection of transcriptional and metabolite networks that controls these processes. The ultimate goal is to understand how key metabolic interactions at low-pH contribute to the ecologically and clinically important properties of oral biofilms, such as selection for cariogenic bacteria, pH recovery in health associated communities, and cell-cell communication. The candidate, Dr. Edlund, has a longstanding interest and history in studying bacterial ecological functions in the environment and therefore, ecology studies of oral communities is a logical extension of her research. Her career trajectory after the mentored phase of this K99 is to become an assistant professor at a leading academic research institute, where she hopes to continue and further her research program on oral biofilms, perform teaching responsibilities, and train future scientists. Dr. Edlund believes that in the long-term, once more is known about how oral biofilms are regulated, her findings will provide important information to developing new drugs to treat and prevent oral diseases. This K99/R00 proposal is designed to complement Dr. Edlund's prior research experience and to provide her with substantive and necessary technical and intellectual expertise as well as the confidence to function as an independent investigator. The candidate will receive her K99 training at the renowned institution UCLA, which will put her in a prime position to move on to similarly ranked Universities. Dr. Edlund's choices of primary mentor, Dr. Shi, and co-mentors, Dr. Dorrestein and Dr. McLean were carefully selected for their relevant, diverse, and complementary expertise to cover all elements of her proposal. In addition, Dr. Edlund has assembled an advisory committee consisting of a diverse group of basic scientists and physicians to oversee her scientific progression and career development throughout her transition to becoming an independent investigator.