Genetic Analysis of the Transcriptional Network Governing C. albicans Biofilms

项目摘要/摘要 酵母菌白色念珠菌是人类消化道的一种正常居留物。它也是最常见的 人类的真菌病原体，引起粘膜和全身感染，特别是在免疫方面 有危险的病人。这项建议试图了解白色念珠菌是如何协调形成 生物膜--有弹性的、表面相关的、有组织的细胞团。生物膜的形成与医学有关 因为新的白色念珠菌感染与植入的医疗设备高度相关，这些设备提供了 生物膜形成的高效底物。这项提案中概述的研究生物膜形成的方法是 通过解剖控制这一过程的转录网络。最终的目标是理解 回路的单个靶基因如何影响生物膜的关键特性，如药物 抵抗、细胞间黏附、细胞间通讯和细胞外基质的产生。 候选人纳比尔博士对研究有着长期的兴趣和历史。她在战后的职业轨迹 K99的指导阶段是成为一家领先的学术研究机构的助理教授， 她希望在那里继续和深化她的生物膜研究计划，进行一些教学 责任，培养未来的科学家。奈比尔博士认为，从长远来看，人们再次了解 如何监管生物膜，她的发现将为开发新药和 用于治疗和预防的疫苗。 这份K99/R00提案旨在补充Nobile博士之前的研究经验，并为她提供 具有实质性和必要的技术和智力专业知识，并有信心作为 独立调查员。她将在K99阶段接受的培训将极大地促进她的职业生涯 前景，并使她在顶尖研究机构的教员职位上具有极强的竞争力。纳比尔医生的 主要导师约翰逊博士和共同导师安第斯博士的选择是经过精心挑选的， 不同的和互补的专业知识，涵盖她提案的所有要素。导师和共同导师都是 资金充足，在各自领域得到国际认可，并且非常富有成效。此外，Dr。 Nobile组建了一个咨询委员会，由不同的基础科学家和医生组成 监督她的科学进步和职业发展，在她向 独立调查员。该委员会的所有成员都是资深科学家/内科医生，具有广泛的 指导和建议博士后过渡到独立的学术生涯的经验。

Project Summary/Abstract The yeast Candida albicans is a normal resident of the human digestive tract. It is also the most common fungal pathogen of humans, causing both mucosal and systemic infections, particularly in immune compromised patients. This proposal seeks to understand how C. albicans orchestrates the formation of biofilms - resilient, surface-associated, organized groups of cells. Biofilm formation is medically relevant because new C. albicans infections are highly correlated with implanted medical devices, which provide efficient substrates for biofilm formation. The approach to studying biofilm formation outlined in this proposal is through dissection of the transcriptional network that controls this process. The ultimate goal is to understand how the individual target genes of the circuit contribute to the key properties of biofilms, such as drug resistance, cell-cell adhesion, cell-cell communication, and production of extracellular matrix. The candidate, Dr. Nobile, has a longstanding interest and history in 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 biofilms, perform some teaching responsibilities, and train future scientists. Dr. Nobile believes that in the long-term, once more is known about how biofilms are regulated, her findings will provide important information to developing new drugs and vaccines to treat and prevent them. This K99/R00 proposal is designed to complement Dr. Nobile'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 training she will receive in the K99 phase will substantially enhance her career prospects, and make her highly competitive for faculty positions in top tier research institutes. Dr. Nobile's choices of primary mentor, Dr. Johnson, and co-mentor, Dr. Andes, were carefully selected for their relevant, diverse, and complementary expertise to cover all elements of her proposal. Both mentor and co-mentor are well-funded, internationally-recognized in their respective fields, and extremely productive. In addition, Dr. Nobile 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. All members of this committee are senior scientists/physicians with extensive experience in mentoring and advising postdocs as they transition to an independent academic career.