Discovery of Chemical Probes and Therapeutic Leads, Phase II

化学探针和治疗先导化合物的发现，第二阶段

• 批准号: 10654734
• 负责人: JOSEPH M FOX
• 金额: $ 240万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10654734
• 关键词: Adjuvant; Analytical Chemistry; Award; Biochemistry; Biological; Biology; Capsid; Cells; Centers of Research Excellence; Chemicals; Collaborations; Communicable Diseases; Complement; Core Facility; Custom; Delaware; Disease; Engineering; Enzymes; Extramural Activities; Faculty; Faculty Recruitment; Funding; Goals; Grant; HIV; Human; Human Biology; Immune response; Infrastructure; Kinetics; Laboratories; Legionnaires' Disease; Lung; Macromolecular Complexes; Malignant Neoplasms; Mass Spectrum Analysis; Mentors; Messenger RNA; Microscopy; Molecular; Molecular Target; Pathway interactions; Phase; Pilot Projects; Regulation; Research; Research Personnel; Resource Sharing; Services; Structure; Therapeutic; Tuberculosis; Universities; Virus; catalyst; cohort; demethylation; design; human disease; instrumentation; interest; member; multidisciplinary; nanoparticle; nucleotide analog; pathogenic bacteria; professor; programs; recruit; screening; small molecule; success; tool; vaccine development

Project Summary The goal of this Center of Biomedical Research Excellence is to continue our efforts to develop molecular approaches for probing biology, to discover and apply new chemical biology tools for the study of biological pathways associated with disease, and to develop computational approaches for understanding small molecule interactions with complex macromolecular targets. With core strengths in synthesis, biochemistry, engineering and biology, our scientific team will develop new chemical biology tools for understanding the cellular and molecular mechanisms that bacterial pathogens use to survive and replicate inside host cells, new chemical tools and nucleotide analogs to understand the regulation of mRNA demethylation by a ‘methyl eraser’ enzyme and its dysregulation in human cancer, molecularly-defined nanoparticle adjuvants that yield specific immune responses in the lung to advance inhalable vaccine development, and computational approaches to elucidate the mechanisms by which small molecules regulate the structure and function of virus capsids. COBRE funding will be used to recruit two new faculty members who will complement the existing strengths of our center, which will be expanded through competitive pilot grants. In years 4 and 5 of the COBRE, five two- year replacement projects will be funded. Collaboration and resource sharing in the Delaware and national IDeA network will be critical for maximizing our research capacity, core facilities and mentoring network. In Phase II, this COBRE continue to develop unique core facilities that facilitates high throughput synthesis, purification, screening and analysis of chemical probes. Building on the infrastructure established in Phase I, we will support a core facility in Analytical Chemistry, which will provide support for critical core facilities in mass spectrometry, solution NMR and kinetic analysis. The center will also support a Synthesis and Discovery core facility, which will provide custom synthesis services and instrumentation and infrastructure for small molecule synthesis, high throughput catalyst discovery, parallel synthesis, computation and microscopy.

项目概要 该生物医学卓越研究中心的目标是继续努力开发分子生物学 探索生物学的方法，发现和应用新的化学生物学工具来研究生物 与疾病相关的途径，并开发计算方法来理解小 分子与复杂大分子靶标的相互作用。拥有合成、生物化学等核心优势， 工程和生物学，我们的科学团队将开发新的化学生物学工具来理解 细菌病原体在宿主细胞内生存和复制的细胞和分子机制，新 化学工具和核苷酸类似物来了解“甲基”对 mRNA 去甲基化的调节 擦除酶及其在人类癌症中的失调，分子定义的纳米颗粒佐剂，产生 肺部的特异性免疫反应，以推进可吸入疫苗的开发和计算 阐明小分子调节病毒结构和功能机制的方法 衣壳。 COBRE 资金将用于招募两名新教员，以补充现有的优势 我们的中心将通过竞争性试点拨款进行扩大。在 COBRE 的第 4 年和第 5 年，有五个二- 年更换项目将获得资助。特拉华州和国家的合作和资源共享 IDeA 网络对于最大化我们的研究能力、核心设施和指导网络至关重要。在 第二阶段，COBRE 继续开发独特的核心设施，促进高通量合成， 化学探针的纯化、筛选和分析。在第一阶段建立的基础设施的基础上， 我们将支持分析化学领域的核心设施，该设施将为分析化学领域的关键核心设施提供支持 质谱、溶液核磁共振和动力学分析。该中心还将支持综合和发现 核心设施，将为小型企业提供定制合成服务以及仪器和基础设施 分子合成、高通量催化剂发现、并行合成、计算和显微镜。