MicroCal Auto-iTC200; automated high sensitivity isothermal titration calorimetry

MicroCal Auto-iTC200；

• 批准号: 7793137
• 负责人: Christie G. Brouillette
• 金额: $ 25万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-11-20 至 2010-11-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7793137
• 关键词: Affinity; Anthrax disease; Antibodies; Automation; Binding; Biological; Biomedical Research; Calorimetry; Charge; Core Facility; Engineering; Evaluation; Fees; Funding; Generations; Grant; Housing; Human Resources; Label; Lipids; Maintenance; Malignant Neoplasms; Minor; Mitochondrial Proteins; Molecular Structure; Mutation; National Institute of Allergy and Infectious Disease; National Institute of Dental and Craniofacial Research; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of General Medical Sciences; Nucleic Acids; Plague; Postdoctoral Fellow; Preclinical Drug Development; Protein translocation; Proteins; Reproduction spores; Research Infrastructure; Robotics; Schools; Science; Solutions; Structure; System; TNFRSF5 gene; Techniques; Thermodynamics; Time; Titrations; Tularemia; United States National Institutes of Health; cost; experience; instrument; macromolecule; malignant breast neoplasm; research study; small molecule; stoichiometry

DESCRIPTION (provided by applicant): Acquisition of the MicroCal Auto-iTC System will support NIH-funded projects from PIs across the UAB campus and Emory who require a quantitative and complete thermodynamic evaluation of the molecular interactions of biological macromolecules. Four major and 8 minor users who represent 7 departments and 4 schools and an additional 7 minor users with pending NIH grants or other support representing 3 departments and 2 schools will be served by this instrument. Isothermal titration calorimetry (ITC) has been successfully used in many applications to study a diverse range of systems including those proposed by our user group as described here, e.g., the interactions of small molecules, proteins, antibodies, nucleic acids and lipids; the effects of mutations and molecular structure changes on binding mechanism and the effect of binding on bound structure. ITC is unique in its ability to quantitate the affinity, stoichiometry and the thermodynamic parameters of binding in a single experiment (?H, ?S, ?G in one experiment; ?Cp in ~3 experiments). There simply is no other technique that can not provide the breadth of information in so little time nor with so little material for interactions in solution and furthermore no extrinsic labeling is required. The MicroCal Auto-iTC200 System is the newest generation ITC offered by MicroCal and it is unrivaled with respect to its sensitivity and automation; in fact, there is no other robotic ITC commercially available and this feature makes it ideal for a multi-user core facility. The PI, Dr. Brouillette, and her senior research associate, Dr. Protassevitch, each have about 30 years of calorimetry experience. They currently manage a biomolecular analysis core within UAB's Comprehensive Cancer Facility which offers a Biacore2000 and a MicroCal automated capDSC to users. This functioning core, with current users across campus, is physically housed within the Center for Biophysical Sciences and Engineering (CBSE). If the present grant is funded, the AutoiTC200 System will also be housed and administered through this existing core facility. Infrastructure support and space is provided by the CBSE. A reasonable user fee will be charged to cover routine maintenance and oversight by the experienced personnel. Additional assistance will be provided at an additional cost. As an example of the breadth of biomedical research which would be supported by this instrument, the NIH grant titles for the four major users are given: NIAID U01 "Discovery and Preclinical Development of Drugs for Anthrax, Plague and Tularemia;" NIDCR R01 "Determination of the SAG Binding Motif on Agl/II of Streptococcous Mutans;" NCI P50 project 1 "SPORE in Breast Cancer;" NIGMS R01 "Structural and Functional Studies for Mitochondrial Protein Translocations;" and NIDDK "Structural and Functional Studies of Hsp40."

描述（由申请人提供）：收购MicroCal Auto-iTC系统将支持UAB校园和Emory的PI的NIH资助项目，这些项目需要对生物大分子的分子相互作用进行定量和完整的热力学评估。代表7个部门和4所学校的4个主要用户和8个次要用户，以及代表3个部门和2所学校的另外7个次要用户，他们将获得NIH赠款或其他支持。等温滴定量热法（ITC）已成功地用于许多应用中，以研究各种各样的系统，包括我们的用户组提出的系统，如本文所述，小分子、蛋白质、抗体、核酸和脂质的相互作用;突变和分子结构变化对结合机制的影响;结合对结合结构的影响。ITC的独特之处在于它能够在一个单一的实验中定量结合的亲和力、化学计量和热力学参数（？H，？S，？在一个实验中，？在~3个实验中的Cp）。没有其他技术不能在如此短的时间内提供如此广泛的信息，也没有如此少的材料用于溶液中的相互作用，而且不需要外部标记。MicroCal Auto-iTC 200系统是MicroCal提供的最新一代ITC，其灵敏度和自动化程度无与伦比;事实上，目前市场上没有其他机器人ITC，这一功能使其成为多用户核心设施的理想选择。PI Brouillette博士和她的高级研究助理Protassevitch博士都有大约30年的热量测量经验。他们目前在UAB的综合癌症设施内管理生物分子分析核心，该设施为用户提供Biacore 2000和MicroCal自动capDSC。这个功能核心，目前的用户遍布校园，物理上位于生物物理科学与工程中心（CBSE）内。如果目前的拨款获得资助，AutoiTC 200系统也将通过现有的核心设施进行安装和管理。基础设施支持和空间由CBSE提供。将收取合理的用户费用，以支付经验丰富的人员的日常维护和监督费用。将提供额外的援助，但需支付额外费用。作为这一工具将支持的生物医学研究广度的一个例子，给出了四个主要用户的NIH赠款标题：NIAID U 01“炭疽、鼠疫和兔热病药物的发现和临床前开发”; NIDCR R 01“变形链球菌Agl/II上SAG结合基序的测定”; NCI P50项目1“乳腺癌中的孢子”;“NIGMS R 01“线粒体蛋白质易位的结构和功能研究;”和NIDDK“HSP 40的结构和功能研究。"