COBRE: LOUISVILLE RES FOUND INC: CORE C: MOLECULAR MODELING FACILITY

COBRE：LOUISVILLE RES FOUND INC：Core C：分子建模设施

• 批准号: 7171226
• 负责人: John O Trent
• 金额: $ 8.18万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7171226
• 关键词: biomedical facility; drug discovery /isolation; neoplasm /cancer chemotherapy; structural biology

DESCRIPTION (provided by applicant): The University of Louisville Molecular Targets Center of Biomedical Research Excellence application (MTCOBRE) is focused on the identification of novel molecular targets for cancer therapy using the techniques of modern structural biology. The two major objectives of this proposal are to ensure the success of junior investigators who are members of the Molecular Targets Program at the University of Louisville and to discover new approaches to the therapy of cancer. The Specific Aims of the Molecular Targets COBRE application are to: 1. Foster successful independent research careers for each of the five principal investigators leading to independent R01 grants. 2. Further build our existing core facilities which will enhance the research capability of the five principal investigators and the other members of the program. 3. Continue to develop our Molecular Targets Program as a cohesive research program which will promote collaborative research projects and increase funding opportunities. 4. Develop an internationally and nationally recognized program which will attract the very best graduate students, postdoctoral fellows and additional faculty. 5. Most importantly, make discoveries leading to new and more effective treatments for patients with cancer. The five related projects of this MT-COBRE application will address a broad spectrum of molecular targets. The specific problems being investigated are: 1) Characterization and manipulation of an inducible isoform of 6-phosphofructo-2-kinase (iPFK-2), a major controller of glucose metabolism in malignant cells. 2) Development and testing of small molecular antagonists of monocyte/macrophage migration inhibitory factor (MIF) recently found to play an important role in carcinogenesis. 3) Elucidation of the signaling mechanisms involved in the activation-dependent lipid signaling enzyme, sphingosine kinase, and its product, sphingosine-l-phosphate, in control of cell proliferation, survival and migration. 4) Use of triplex forming oligonucleotides to target Bleomycin to the Her2/neu gene. 5) A crystallographer/biologist is being recruited to study molecular interactions important in the TRAF signaling pathway. The overarching theme of this program is the use of structural biology to develop novel strategies for therapy of neoplastic disease. We believe that these five projects, along with those of the other members of the program, represent a coherent approach to the application of modern structural biology to translational cancer research.

描述(由申请人提供)： 路易斯维尔大学分子靶标生物医学研究卓越应用中心(MTCOBRE)致力于利用现代结构生物学技术识别癌症治疗的新分子靶标。这项提议的两个主要目标是确保路易斯维尔大学分子靶标计划成员的初级研究人员的成功，并发现癌症治疗的新方法。分子靶标Cobre应用的具体目标是： 1.为获得独立R01赠款的五名主要研究人员中的每一人培养成功的独立研究生涯。 2.进一步建设我们现有的核心设施，将增强五名主要调查人员和项目其他成员的研究能力。 3.继续发展我们的分子目标计划，作为一个具有凝聚力的研究计划，将促进合作研究项目并增加资助机会。 4.开发一个国际和国家认可的项目，吸引最优秀的研究生、博士后研究员和更多的教师。 5.最重要的是，为癌症患者带来新的、更有效的治疗方法。 这项MT-Cobre应用的五个相关项目将涉及广泛的分子靶标。正在研究的具体问题包括：1)可诱导的6-磷酸果糖-2-激酶(iPFK-2)亚型(iPFK-2)的特性和操作，iPFK-2是恶性肿瘤细胞中葡萄糖代谢的主要控制者。2)最近发现在肿瘤发生中起重要作用的单核/巨噬细胞移动抑制因子(MIF)小分子拮抗剂的开发和检测。3)阐明激活依赖的脂信号转导酶鞘氨醇激酶及其产物鞘氨醇L磷酸参与控制细胞增殖、存活和迁移的信号机制。4)利用三链形成寡核苷酸将博莱霉素靶向Her2/neu基因。5)正在招募一名结晶学家/生物学家来研究TRAF信号通路中重要的分子相互作用。该计划的主要主题是使用结构生物学来开发治疗肿瘤疾病的新策略。我们相信，这五个项目以及该计划其他成员的项目，代表了将现代结构生物学应用于转译癌症研究的一种连贯的方法。