Structural Biology

结构生物学

• 批准号: 8104144
• 负责人: JOHN Hackett BUSHWELLER
• 金额: $ 1.49万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8104144
• 关键词: Area; Arts; Atomic Force Microscopy; Cell Signaling Process; Chemistry; Chromosome Structures; Complement; Complex; Development; Direct Costs; Drug Delivery Systems; Drug Design; Electron Microscopy; Epigenetic Process; Faculty; Funding; Future; Genetic Transcription; Goals; Grant; Guanosine Triphosphate Phosphohydrolases; Head; Institution; Integral Membrane Protein; Macromolecular Complexes; Malignant Neoplasms; Membrane Proteins; Methods; Molecular; Multi-Drug Resistance; Mutagenesis; Mutation; National Institute of General Medical Sciences; Oncogenes; Play; Proteins; Publications; Regulation; Research; Research Peer Review; Research Personnel; Resolution; Role; Science; Signal Transduction; Structure; Testing; Therapeutic; Translating; Tumor Suppressor Proteins; Ursidae Family; Work; base; biological systems; carcinogenesis; college; design; insight; macromolecule; medical schools; member; novel; novel therapeutics; programs; protein function; research study; structural biology; structural genomics; therapeutic target; three dimensional structure; transcription factor; trend

The goal of the Structural Biology Program (Program 5) is to bring a wide range of structural approaches to bear on the proteins involved in carcinogenesis, use this structural information to gain hovel insights into function, and to translate this understanding into novel therapeutic strategies. Detailed understanding of molecular function in biological systems requires information about the 3D structures of macromolecules. This information can range from very high-resolution structural information derived from x-ray or NMR studies to lower resolution structural information from electron microscopy or atomic force microscopy. In all cases, however, the wealth of information available from structural studies of macromolecules using these approaches provides novel and powerful insights into function. Such information is critical for understanding the functions of proteins involved in carcinogenesis as it provides a meaningful framework to design experiments to test function, for example by highly selective mutagenesis. Structures give a basis for understanding the alteration in function that accompany naturally occurring mutations in cancer, either in oncogenes or tumor suppressor proteins. In addition, structural studies by such biophysical methods provide the basis for initiating programs of targeted drug design that are clearly the paradigm for future development of targeted cancer therapeutics. The Program is comprised of 15 investigators from five Departments, four from the School of Medicine and one (Department of Chemistry) from the College of Arts and Sciences. This group of investigators has $8.8M in yearly direct costs from peer-reviewed research funding, including $390K from NCI. Members of the Program have played prominent roles in the structural genomics efforts underway here in the US. In addition, three faculty members are the Pis on large multi-investigator multi-institution grants. During the last grant period, the Program in Structural Biology has generated a total of 230 publications with 27% intra-programmatic publications and 12% inter-programmatic publications.

结构生物学计划（计划5）的目标是带来广泛的结构方法 要承担涉及致癌的蛋白质，请使用这些结构信息来获得Hovel的见解 功能，并将这种理解转化为新的治疗策略。 对生物系统中分子功能的详细了解需要有关3D的信息 大分子的结构。此信息的范围从非常高分辨率的结构信息范围 源自X射线或NMR研究，从电子显微镜或 原子力显微镜。但是，在所有情况下，从结构研究中获得的丰富信息 使用这些方法的大分子为功能提供了新颖而有力的见解。这样的 信息对于理解癌变的蛋白质功能至关重要，因为它提供了 设计实验以测试功能的有意义的框架，例如通过高度选择性诱变。 结构为理解自然发生的功能变化提供了基础 癌症或肿瘤抑制蛋白中的癌症突变。另外，通过这种结构研究 生物物理方法为启动目标药物设计计划提供了基础，显然是 范式未来开发有针对性的癌症治疗剂。 该计划由来自五个部门的15名调查人员组成，其中4个来自医学院 以及一位艺术与科学学院的（化学系）。这组调查员有 由同行评审的研究资金获得880万美元的年度直接费用，其中包括NCI的3.9万美元。成员 该计划在美国正在进行的结构基因组学工作中发挥了重要作用。在 此外，三名教职员工是大型多侵略者多机构赠款的PI。 在最后一个赠款期间，结构生物学计划总共产生了230个出版物 有27％的截面出版物和12％的程序间出版物。