AREA I BIOMOLECULAR STRUCTURE & FUNCTION: AIDS

I 区生物分子结构

• 批准号: 7336058
• 负责人: DAVID CALHOUN
• 金额: $ 31.04万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7336058
• 关键词: AREA; BIOMOLECULAR; STRUCTURE; FUNCTION; AIDS

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NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。主要领域I的目标是阐明生物分子的结构和功能，目的是理解和解释它们在发育和细胞事件中的功能。为期五年的更新的一个主要新举措是在X射线衍射领域招募一名新的教员，以确定蛋白质结构，并提供启动资金来装备该设施。我们要求雇用一名X射线晶体学家，是因为需要补充和加强核磁共振正在进行的结构工作。我们还获得了诺华捐赠的X射线晶体学设备，并通过CCNY新的Pathways生物信息学和生物技术中心的学院资金建立。 生物化学和结构生物学的最新发展使I区的成员能够进一步扩展他们的研究领域，进入大分子和大分子组装。为了提高生产力和竞争力，他们必须利用新技术，并转向增加使用核磁共振技术与核磁共振设施，这是不可或缺的纽约市结构生物学中心，正式在我们的校园2002年12月16日开幕。雅阁这一目标，我们在I区增加了一位核磁共振光谱学专家Ronnie Ghose博士。这项雇用是由RCMI在我们的最后一次赠款续期批准。他开发了一个令人兴奋的独立研究项目，并获得了校外资金。他积极与第一区的所有成员和其他地区的成员互动。我们的设备不断改进和更新。在过去的一年中，一台500兆赫和一台600兆赫的光谱仪已经交付，并在Marshak科学大楼的广场层投入使用。这些机器的费用由学院和RCMI分摊。这种新的能力将质谱法的使用进一步扩展到大型和脆弱的分子，并使生物科学的研究人员可以使用这种工具。Barbara Zajc在生物有机化学领域的当前赠款期间被RCMI基金雇用。她研究了DNA致癌物结合物，氟作为生物活性的调节剂，并监测这些修饰导致的结构变化。 我们的中心设施现在有两个分子动力学磷光成像仪和一个分子动力学激光密度计，这些对RCMI的每个人都很有用。 区域I教师和研究亮点的成就大部分区域I教师（Balogh-Nair，Ghose，Gunner，Lazartists，Schulz，Tasayco，Zajc）都得到了外部赠款的资助。 舒尔茨博士被邀请撰写一本书的章节，题为真核生物中脂肪酸的氧化，他在美国国立卫生研究院的医学生物化学研究科任职。 Gunner博士获得了总统科学家和工程师早期职业奖（PECASE），奖金为50万美元。 教师研究总结 Balogh-Nair博士（化学）从事树枝状聚合物的合成，对M-嗜性HIV-1病毒株具有增强的活性。 与传统的聚合物相比，树枝状聚合物是独特的核-壳结构，具有三个基本的结构组分：（a）核，（B）由重复的分支细胞单元组成的壳的内部（代），和（c）末端官能团，即，外壳或外围。 Ghose博士专注于开发和实施新型NMR技术，以探测生物分子的结构和动力学。他还对破译参与Src信号通路的关键酶的结构-功能关系感兴趣。他最近在《生物分子核磁共振杂志》上发表了一篇关于探测蛋白质缓慢相关运动的新型核磁共振方法的论文。 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）分析电子和质子的功能，其中侧链或底物电离状态对功能很重要，以及（c）调查蛋白质结构数据库以确定稳定隐藏电荷的基序。 在过去的一年里，Lazarlett博士通过开发脂质双层中蛋白质的有效能量函数作为其EEF 1水溶液能量函数的延伸，在膜蛋白建模方面迈出了一大步。 Schulz博士（生物化学）的主要目标是详细了解不饱和脂肪酸和羟基脂肪酸的b-氧化所需的反应和辅助酶。 Tasayco博士（生物化学）是RCMI的一名雇员，他在《生物化学》杂志上发表了一篇开创性的论文，利用差示扫描量热法识别互补无序蛋白质片段家族中具有残留结构的区域。她目前正在通过NMR光谱研究蛋白质未折叠状态下的残留结构，为蛋白质能量学的预测提供基准。 Zajc博士研究化学致癌领域的结构-活性关系（SAR）。具体来说，她正在解决的DNA致癌物共轭物的SAR研究，通过位点特异性掺入氟作为生物活性的调节剂，以评估发生这种修改后的结构变化。