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）：微局部自动ITC系统的获取将支持来自UAB校园和Emory的NIH资助的项目，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。该工具将为四个主要和8个未成年人用户，他们代表7个部门和4所学校以及另外7个由NIH赠款或其他代表3个部门和2所学校的支持的未成年人用户。等温滴定量热法（ITC）已在许多应用中成功使用，以研究各种系统，包括此处所述的用户组提出的系统，例如，小分子，蛋白质，抗体，核酸，核酸和脂质的相互作用；突变和分子结构的影响变化对结合机制以及结合对结构结构的影响。 ITC在单个实验中定量结合的亲和力，化学计量和结合的热力学参数的能力是独一无二的（在一个实验中；？cp;？cp in 〜3实验中）。根本没有其他技术在很少的时间内无法提供信息广度，也无法提供较少的材料以进行溶液中的互动，而且不需要外部标签。 Microcal Auto-ITC200系统是Microcal提供的最新一代ITC，它的灵敏度和自动化是无与伦比的；实际上，没有其他商业上的机器人ITC可用，此功能使其非常适合多用户核心设施。 PI，Brouillette博士和她的高级研究助理Protassevitch博士，每个人都有大约30年的量热法。他们目前在UAB的综合癌症设施中管理生物分子分析核心，该机构为用户提供了BIACORE2000和Microcal自动化CAPDSC。该功能性核心在校园各地的当前用户都位于生物物理科学与工程中心（CBSE）中。如果目前的赠款是资助的，则AutoITC200系统还将通过此现有核心设施进行容纳和管理。 CBSE提供了基础架构支持和空间。经验丰富的人员将收取合理的用户费用以涵盖常规维护和监督。将以额外费用提供额外的帮助。作为该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 U01“发现和临床前炭疽病，瘟疫和疾病的临床前开发；” NIDCR R01“测定链球菌突变的AGL/II上的SAG结合基序的测定；” NCI P50项目1“乳腺癌中的孢子”； NIGMS R01“线粒体蛋白易位的结构和功能研究；” NIDDK“ HSP40的结构和功能研究”。