Genetic Analysis of the Transcriptional Network Governing C. albicans Biofilms

白色念珠菌生物膜转录网络的遗传分析

基本信息

批准号：
8835216
负责人：
Clarissa Jane Nobile
金额：
$ 24.9万
依托单位：
UNIVERSITY OF CALIFORNIA, MERCED
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8835216
关键词：
Adherence Advisory Committees Animal Model Animals Antifungal Agents Antimicrobial Resistance Back Behavior Biochemical Biological Assay Blood Candida albicans Candidate Disease Gene Catheters Cell Communication Cell-Cell Adhesion Cells Characteristics Committee Members Communities Complement Data Dentures Development Disease Dissection Drug resistance Ectopic Expression Educational process of instructing Elements Environment Extracellular Matrix Faculty Funding Future Gastrointestinal tract structure Gene Chips Gene Targeting Genes Genetic Genome Goals Growth Human Immune Immune system Immunocompetent Immunocompromised Host Implant In Vitro Individual Infection Knock-out Knowledge Laser Scanning Confocal Microscopy Lead Libraries Life Maintenance Maps Mass Spectrum Analysis Mechanics Medical Device Mentors Microbe Microbial Biofilms Microscopy Modeling Monitor Morbidity - disease rate Nature Patients Pharmaceutical Preparations Phase Physicians Physiological Positioning Attribute Postdoctoral Fellow Process Production Property Proteins Rattus Recording of previous events Research Research Institute Research Personnel Resistance Resolution Role Scientist Senior Scientist Signaling Molecule Skin Tissue Soft Tissue Infections Source Surface Suspension substance Suspensions Systemic infection Testing Training Vaccines Venous Virulent Yeasts abstracting base career career development chromatin immunoprecipitation design experience feeding genetic analysis improved in vitro testing in vivo in vivo Model intercellular communication interest microorganism mortality mutant pathogen prevent professor programs research study transcription factor transcriptome sequencing

项目摘要

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.

项目摘要/摘要酵母白色念珠菌是人类消化道的普通居民。这也是最常见的人类的真菌病原体，引起粘膜和全身感染，特别是在免疫中受损的患者。该建议旨在了解白色念珠菌如何策划形成生物膜 - 弹性，表面相关的，有组织的细胞组。生物膜形成在医学上相关因为新的白色念珠菌感染与植入的医疗设备高度相关，这提供了生物膜形成的有效底物。研究该提案中概述的生物膜形成的方法是通过解剖控制此过程的转录网络。最终目标是了解电路的单个靶基因如何促进生物膜的关键特性，例如药物电阻，细胞 - 细胞粘附，细胞 - 细胞通信以及细胞外基质的产生。候选人Nobile博士对研究有着长期的兴趣和历史。她的职业轨迹之后该K99的指导阶段是成为一家领先的学术研究所的助理教授，她希望继续进行生物膜研究计划，进行一些教学责任，培训未来的科学家。 Nobile博士认为，从长远来看，再次知道如何调节生物膜，她的发现将为开发新药和疫苗以治疗和防止它们。该K99/R00提案旨在补充Nobile博士先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，以及充满信心的信心独立研究者。她将在K99阶段接受的培训将大大改善她的职业生涯前景，使她在顶级研究机构的教职员工职位上具有很高的竞争力。 Nobile博士小学导师约翰逊博士和联合学博士安第斯山脉博士的选择是为了他们的相关性而精心挑选的多元化和补充专业知识，以涵盖其提议的所有要素。导师和同事都是资金充足的，国际在各自的领域中得到了公认，并且富有成效。另外，博士 Nobile组建了一个由一群基础科学家和医生组成的咨询委员会在整个过渡到成为一个独立研究者。该委员会的所有成员都是高级科学家/医师，在过渡到独立学术职业时，具有指导和建议的经验。