HISTATIN RECEPTORS AS DRUG TARGETS FOR ORAL CANDIDIASIS

组氨酸受体作为口腔念珠菌病的药物靶点

• 批准号: 6164397
• 负责人: Mira Edgerton
• 金额: $ 8.36万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6164397
• 关键词: Candida albicans; HIV infections; antiAIDS agent; antifungal agents; binding proteins; candidiasis; complementary DNA; computer assisted sequence analysis; drug resistance; fungal genetics; fungal proteins; gene expression; genetic library; human tissue; laboratory rabbit; mass spectrometry; membrane potentials; membrane transport proteins; nucleic acid sequence; opportunistic infections; pathologic process; polymerase chain reaction; protein structure function; saliva; virulence

This is a new application for an Independent Scientist Award (K02) for Dr. Mira Edgerton, and it accompanies the already funded R01DE12159 grant. Dr. Edgerton has a D.D.S. degree, specialty training in prosthodontics, and a Ph.D. in Oral Biology. She is an Assistant Professor in the Departments of Restorative Dentistry and Oral Biology at the State University of New York at Buffalo (SUNYAB). Dr. Edgerton's research has focused on characterizing the structural elements of salivary histatins required for candidacidal activity as well as the cellular mechanism of action of histatins with Candida albicans. Her work has identified a C. albicans membrane protein (HstBP) which is a yeast receptor protein of the histatin candidacidal pathway. The current research project will clone and sequence the C. albicans HstBP gene and examine its expression as a virulence or resistance factor in yeast from HIV-oropharyngeal candidiasis patients. Dr. Edgerton's immediate goals are to use the most current techniques in yeast molecular genetic to identify mechanisms of C. albicans pathogenicity in the oral cavity. Her long range goals are to define the molecular basis of virulence, pathogenesis and drug resistance of C. albicans in order to develop better treatment modalities for local and systemic candidiasis. Achievement of these goals is possible only through acquisition of an in-depth background in yeast molecular genetics and knowledge of the most current systems fir eukaryotic genetics. Dr. Edgerton's scientific career would be advanced through this additional training and experience. The research environment in the Department of Oral Biology at SUNYAB in combination with experiences in the laboratories of other yeast molecular geneticists is excellent for development of the research career of Dr. Edgerton. However, her clinical teaching duties limit the time available to her for acquiring these additional research skills. This ISA application is to obtain salary support to release Dr. Edgerton from her clinical teaching and committee responsibilities in order to devote 80% of her full time professional effort to research activities. This award would provide her the opportunity to extend her background in yeast biology to the molecular level and apply this new expertise to studies of virulence and pathogenesis of oral and systemic candidiasis.

这是 Mira Edgerton 博士申请独立科学家奖 (K02) 的新申请，它与已经资助的 R01DE12159 赠款一起提供。埃哲顿博士患有 D.D.S.学位、修复学专业培训和博士学位。在口腔生物学中。她是纽约州立大学布法罗分校 (SUNYAB) 修复牙科和口腔生物学系的助理教授。 Edgerton 博士的研究重点是表征念珠菌活性所需的唾液组蛋白的结构元件，以及组蛋白与白色念珠菌作用的细胞机制。她的工作鉴定了一种白色念珠菌膜蛋白 (HstBP)，它是组蛋白念珠菌途径的酵母受体蛋白。目前的研究项目将克隆白色念珠菌 HstBP 基因并对其进行测序，并检查其在 HIV 口咽念珠菌病患者酵母中作为毒力或耐药因子的表达。 Edgerton 博士的近期目标是利用最新的酵母分子遗传学技术来确定口腔中白色念珠菌的致病机制。她的长期目标是确定白色念珠菌的毒力、发病机制和耐药性的分子基础，以便为局部和全身念珠菌病开发更好的治疗方式。只有通过获得酵母分子遗传学的深入背景和最新真核遗传学系统的知识，才有可能实现这些目标。通过这些额外的培训和经验，埃杰顿博士的科学事业将得到推进。 SUNYAB口腔生物学系的研究环境与其他酵母分子遗传学家实验室的经验相结合，非常有利于Edgerton博士研究生涯的发展。然而，她的临床教学职责限制了她获得这些额外研究技能的时间。此 ISA 申请旨在获得薪资支持，以将 Edgerton 博士从临床教学和委员会职责中解放出来，以便将 80% 的全职专业精力投入到研究活动中。该奖项将为她提供将酵母生物学背景扩展到分子水平的机会，并将这种新的专业知识应用于口腔和全身念珠菌病的毒力和发病机制的研究。