AREA I BIOMOLECULAR STRUCTURE & FUNCTION: AIDS

I 区生物分子结构

• 批准号: 7715272
• 负责人: DAVID CALHOUN
• 金额: $ 27.57万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715272
• 关键词: Address; Area; Award; Benchmarking; Biochemistry; Bioinformatics; Biological; Biological Process; Biological Sciences; Biomolecular Nuclear Magnetic Resonance; Biophysics; Biotechnology; Book Chapters; Carcinogens; Cells; Charge; Chemistry; Complement; Computer Retrieval of Information on Scientific Projects Database; Databases; Dendrimers; Development; Differential Scanning Calorimetry; Disease; EEF1A1 gene; Electrons; Engineering; Enzymes; Equipment; Eukaryota; Eukaryotic Cell; Event; Extramural Activities; Faculty; Family; Fluorine; Funding; Generations; Goals; Grant; HIV-1; Institution; Lasers; Lipid Bilayers; Mass Spectrum Analysis; Medical; Membrane Proteins; Methods; Modeling; Modification; Monitor; Motion; NMR Spectroscopy; New York City; Paper; Pathway interactions; Polymers; Protein Fragment; Protein NMR Spectroscopy; Proteins; Protons; Publications; Publishing; Reaction; Recruitment Activity; Research; Research Personnel; Residual state; Resources; Roentgen Rays; Science; Scientist; Secure; Services; Side; Signal Pathway; Site; Solutions; Source; Specialist; Structural Protein; Structure; Structure-Activity Relationship; Study Section; Surveys; Techniques; United States National Institutes of Health; Viral; Work; Writing; X ray diffraction analysis; X-Ray Diffraction; aqueous; career; chemical carcinogenesis; college; cost; fatty acid oxidation; functional group; hydroxy fatty acid; improved; interest; ionization; macromolecular assembly; macromolecule; member; molecular dynamics; new technology; novel; oxidation; programs; protein function; protein structure; structural biology; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The major Area I goals are to elucidate the structures and functions of biological molecules with the aim of understanding and explaining their functions in development and in cellular events. A major new initiative for the five-year renewal is to recruit a new faculty member in the area of X-ray diffraction for the determination of protein structure and to provide startup funds to equip this facility. Our request for the hire of an X-ray crystallographer is motivated by the need to complement and enhance the ongoing structural work carried out by NMR. We have also secured X-ray crystalography equipment which was donated by Novartis and set up through funds from the college in the new Pathways Bioinformatics and Biotechnology Center at CCNY. Recent developments in biochemistry and structural biology allow members of Area I to further expand their areas of study into large macromolecules and macromolecular assemblies. To be more productive and competitive, they must exploit the new technologies and turn to increased use of NMR techniques in conjunction with the NMR facilities that are integral to the New York City Structural Biology Center that officially opened on our campus December 16, 2002. In accord with this goal we have added a specialist in NMR spectroscopy, Dr. Ronnie Ghose, to Area I. This hire was approved by RCMI in our last grant renewal. He has developed an exciting independent research program and has secured extramural funding. He actively interacts with all members of Area I and members of other areas as well. Our equipment is continually being improved and up-dated. During the past year one 500 and one 600 MHz spectrometers were delivered and put into service on the Plaza Level of the Marshak Science Building. The cost for these machines was split between the College and the RCMI. This new capability expands the use of mass spectrometry further into large and fragile molecules and makes this tool available to researchers in the biological sciences. Barbara Zajc was hired with RCMI funds during the current grant period in the area of Bioorganic Chemistry. She studies DNA-carcinogen conjugates following the incorporation of fluorine as a modulator of biological activity and monitors structural changes that result form these modifications. Our central facility now has two Molecular Dynamics phosphoimagers and a Molecular Dynamics Laser Densitometer and these are of general utility to everyone in RCMI. Accomplishments of Area I Faculty and Research Highlights A majority of the Area I faculty (Balogh-Nair, Ghose, Gunner, Lazaridis, Schulz, Tasayco, Zajc) are well funded by external grants. Dr. Schulz was invited to write a book chapter entitled "Oxidation of Fatty Acids in Eukaryotes" and he serves on the Medical Biochemistry Study Section at the NIH. Dr. Gunner was honored with a Presidential Early Career Award for Scientists and Engineers (PECASE) with a $0.5 million grant. Summary of Faculty Research Dr. Balogh-Nair (Chemistry) is engaged in the synthesis of dendrimers with enhanced activities towards M-tropic HIV-1 viral strains. In contrast to traditional polymers, dendrimers are unique core-shell structures possessing three basic architectural components: (a) a core, (b) an interior of shells (generation) consisting of repetitive branch cell units, and (c) terminal functional groups, I.E., the outer shell or periphery. Dr. Ghose focuses on the development and implementation of novel NMR techniques to probe the structure and dynamics of biomolecules. He is also interested in deciphering the structure-function relationships in key enzymes involved in the Src-signaling pathway. He has recently published a paper in the J. of Biomolecular NMR on novel NMR methods that probe slow correlated motions in proteins. Dr. Gunner (Biophysics), an RCMI hire, is working to (a) develop tools to analyze and compare the energies of charged groups in proteins, (b) analyze the function of electron and proton where side chain or substrate ionization states are important for function, and (c) survey the protein structural data bank to identify motifs that stabilize buried charges. Dr. Lazaridis made a big step forward during the past year towards modeling of membrane proteins by developing an effective energy function for proteins in lipid bilayers as an extension of his EEF1 aqueous solution energy function. Dr. Schulz (Biochemistry) has a major goal to provide a detailed understanding of the reactions and auxiliary enzymes that are specifically required for the b-oxidation of unsaturated and hydroxy fatty acids. Dr. Tasayco (Biochemistry), an RCMI hire, produced a pioneering publication in Biochemistry using differential scanning calorimetry to recognize regions with residual structure in a family of complementary disordered protein fragments. She is currently studying the residual structure in the unfolded state of proteins by NMR spectroscopy to provide benchmarks for the prediction of protein energetics. Dr. Zajc studies the structure-activity relationships (SAR) in the area of chemical carcinogenesis. Specifically, she is addressing the SAR studies of DNA-carcinogen conjugates via site-specific incorporation of fluorine as a modulator of biological activity, to evaluate structural changes that occur upon such modifications.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 第一领域的主要目标是阐明生物的结构和功能 分子的目的是理解和解释它们在发育中的功能 以及细胞事件中。 五年更新的一项重大新举措是招募新的 用于确定蛋白质结构的 X 射线衍射领域的教员 并提供启动资金来装备该设施。 我们要求租用 X 光检查 晶体学家的动机是需要补充和增强正在进行的 通过NMR进行结构工作。 我们还获得了 X 射线晶体学 设备由诺华公司捐赠并由学院资助建立 CCNY 的新 Pathways 生物信息学和生物技术中心。 生物化学和结构生物学的最新发展使 I 区成员能够 进一步将研究领域扩展到大分子和大分子 组件。 为了提高生产力和竞争力，他们必须利用新的 技术，并转向增加将 NMR 技术与 NMR 结合使用 纽约市结构生物学中心的重要设施 2002 年 12 月 16 日在我们的校园开业。根据这一目标，我们增加了 核磁共振波谱学专家 Ronnie Ghose 博士前往 I 区。此次聘用得到了 RCMI 在我们上次拨款续签中。 他开展了一项令人兴奋的独立研究 计划并已获得外部资金。 他积极与所有成员互动 I 区和其他区的成员也是如此。 我们的设备不断改进和更新。 在过去的一年里 500 一台600 MHz光谱仪交付并投入使用 马沙克科学大楼。 这些机器的成本由学院分摊 和 RCMI。 这一新功能将质谱的使用进一步扩展到 大而脆弱的分子，使该工具可供生物研究人员使用 科学。 Barbara Zajc 在当前资助期内受 RCMI 资金聘用，领域包括： 生物有机化学。 她按照以下方法研究 DNA 致癌物结合物： 掺入氟作为生物活性调节剂并监测结构 这些修改导致的变化。 我们的中心设施现在拥有两台分子动力学磷光成像仪和一台分子动力学荧光成像仪 动态激光密度计和这些对于 RCMI 中的每个人来说都是通用的。 一区教师成果及研究亮点 大多数 I 区教师（Balogh-Nair、Ghose、Gunner、Lazaridis、Schulz、Tasayco、 Zajc）有充足的外部赠款资助。 舒尔茨博士受邀撰写书籍章节 题为“真核生物中脂肪酸的氧化”，他在医学界任职 NIH 生物化学研究部。 冈纳博士荣获总统早期奖 科学家和工程师职业奖 (PECASE)，奖金 50 万美元。 教师研究摘要 Balogh-Nair 博士（化学）致力于增强型树枝状聚合物的合成 针对 M 向性 HIV-1 病毒株的活性。 与传统聚合物相比， 树枝状聚合物是独特的核壳结构，具有三种基本结构 组成部分：(a) 核心，(b) 由重复分支组成的壳（生成）内部 细胞单元，以及（c）末端官能团，即外壳或外围。 Ghose 博士专注于新型 NMR 技术的开发和实施 探索生物分子的结构和动力学。他也有兴趣破译 Src 信号通路中关键酶的结构与功能关系。 他最近在《生物分子核磁共振杂志》上发表了一篇关于新型核磁共振方法的论文 探测蛋白质中的慢相关运动。 Gunner 博士（生物物理学）是 RCMI 的一名雇员，他正在致力于 (a) 开发工具来分析和 比较蛋白质中带电基团的能量，(b) 分析电子的功能 和质子，其中侧链或底物电离态对于功能很重要，并且 (c) 调查蛋白质结构数据库以确定稳定埋藏电荷的基序。 Lazaridis 博士在过去的一年里在建模方面迈出了一大步 通过为脂质双层中的蛋白质开发有效的能量功能来制备膜蛋白 作为其 EEF1 水溶液能量函数的延伸。 舒尔茨博士（生物化学）的主要目标是提供对 b-氧化特别需要的反应和辅助酶 不饱和脂肪酸和羟基脂肪酸。 Tasayco 博士（生物化学）是 RCMI 的一名雇员，在 生物化学使用差示扫描量热法识别残留区域 互补无序蛋白质片段家族的结构。 她目前是 通过核磁共振波谱研究蛋白质未折叠状态的残余结构 为蛋白质能量学的预测提供基准。 Zajc 博士研究化学领域的构效关系 (SAR) 致癌作用。 具体来说，她正在讨论 DNA 致癌物的 SAR 研究 通过位点特异性掺入氟作为生物活性调节剂形成缀合物， 评估此类修改后发生的结构变化。