Isothermal Titration Calorimeter

描述（由申请人提供）：分子间相互作用是生物学中的一种基本现象，是从酶活性和调节到细胞信号传导、分子识别和转运等过程的基础。来自威尔康奈尔医学院（WCMC）的8名主要用户和4名次要用户参与了当前的应用程序，以获取等温滴定量热仪（ITC），以表征广泛的分子相互作用的热力学基础。他们的研究兴趣包括蛋白质：细胞信号级联、病毒感染、蛋白质翻译和折叠背后的蛋白质相互作用;蛋白质：膜相互作用，介导折叠;两亲物：膜相互作用，提醒双层物理性质; RNA适体的开发作为遗传编码的分析物传感器;和离子和其他溶质的跨膜运输。这些研究对生物医学科学重大进展的影响反映在NIH向参与研究的研究人员提供的广泛资助中，这些研究人员包括生物化学系的Eliezer，Lu，Radhakrishnan和Wu;生理学和生物物理学系的Andersen，Blanchard，Boudker，Huang，Weinstein，麻醉学系的Accardi和Nimigean以及药理学系的Jeffery。ITC基于对复合物形成时释放或吸收的热量的测量，并提供了一种通用的、无标记的、快速和可靠的手段来（i）检测相互作用;（ii）区分不同的结合模式;和（iii）获得结合的热力学参数，如吉布斯自由能、焓、熵和热容。参与该应用的几位研究人员在使用ITC方面拥有丰富的经验，并在同行评审的高影响力期刊上发表的研究中使用了它。然而，目前的工作受到阻碍，因为养护监测中心没有这样的文书。为了消除这些障碍并提高NIH支持的研究工作的生产力和创造力，我们申请资金购买Auto-iTC 200仪器，这是Microcal生产的最先进的设备，现在是GE Healthcare的一部分。为此，我们总共申请了310，931美元，其中包括购买仪器、软件许可证和两年服务合同的资金。

DESCRIPTION (provided by applicant): Inter-molecular interactions are a fundamental phenomenon in biology and underlie processes ranging from enzymatic activity and regulation to cell signaling, molecular recognition, and transport. A group of 8 major and 4 minor users from Weill Cornell Medical College (WCMC) participate in the current application to acquire an isothermal titration calorimeter (ITC) in order to characterize the thermodynamic bases of a broad range of molecular interactions. Their research interest include protein: protein interactions underlying cell signaling cascades, viral infection, protein translation and folding; protein: membrane interactions, mediating folding; amphiphile: membrane interactions, alerting bilayer physical properties; development of RNA aptamers as genetically encoded analyte sensors; and trans-membrane transport of ions and other solutes. The impact of such studies on major progress in biomedical sciences is reflected in the extensive funding that the NIH has awarded to the participating researchers, which include Eliezer, Lu, Radhakrishnan and Wu from the Biochemistry Department; Andersen, Blanchard, Boudker, Huang, Weinstein from the Department of Physiology and Biophysics, Accardi and Nimigean from the Department of Anesthesiology and Jeffery from the Pharmacology Department. ITC is based on the measurements of heat, released or absorbed upon complex formation, and provides a universal, label-free, rapid and reliable means to (i) detect interactions; (ii) distinguish between different modes of binding; and (iii) obtain the thermodynamic parameters of binding such as the Gibbs free energy, enthalpy, entropy and heat capacity. Several researchers participating in this application have extensive experience in using ITC and have employed it in studies published in peer reviewed high impact journals. However, current work is impeded because no such instrument exists at WCMC. To eliminate these impediments and increase productivity and creativity of the NIH-supported research efforts, we request funding to purchase an Auto-iTC200 instrument, which is state of the art equipment produced by Microcal, now part of GE Healthcare. For this purpose we request a total of $310,931, which includes funding for the instrument acquisition, software licenses and a two-year service contract.