Isothermal titration calorimetry instrumentation for structural biology, biological mechanisms and drug discovery

生物分子相互作用和特征构成了King‘s众多研究项目的基础，从分子机制的基础研究到具有医学和社会影响的更多应用研究。越来越需要提高这些特征的精确度和准确性，以实现对健康和疾病途径和机制的详细了解，促进将这项科学转化为造福社会的结果。用于这类研究的关键技术之一是等温滴定热法(ITC)，它提供了一种通用的方法来详细研究分子如何能够相互作用，例如了解哪种潜在的药物能够更有效地阻断其靶标，细菌如何对抗生素产生抗药性，或解释生命的基本基础。对于King‘s的四个学院的许多小组来说，一个明确而紧迫的需求是改进我们目前可以产生的结果，并能够表征和/或识别在许多领域发挥关键作用的新的生化反应或分子组件，包括宿主-病原体相互作用、天然产品生物合成、衰老、心血管研究、癌症、化学生物学和生物工程、神经疾病、信号通路、哮喘和过敏。这里要求的仪器有望改变国王学院广大用户群体的科学。国王学院是一家领先的国际研究机构，涉及一系列生物学学科，因此投资于在当地提供ITC仪器以增加价值的潜力是巨大的。ITC仪器将成为惠康信托支持的生物分子光谱学中心的一部分，并将与其他方法协同运作，与其他生物物理和结构生物学方法相结合，并促进与其他内部基础设施和平台(例如质谱仪、组学平台、成像)的交流。中心内的环境还将便利来自其他学术机构和/或行业的研究人员的使用，扩大将开展的科学活动的广度。该中心配备了最新的国贸中心仪器，将有助于阐明基础生物科学的分子机制，并允许对生物疗法进行最先进的表征，以根据BBSRC的职权范围和优先事项应对战略挑战。新仪器将加强生物分子光谱学中心的战略使命，为具有国际竞争力的研究提供最高质量的数据，培训新一代科学家掌握尖端方法，促进思想交流，促进新的跨学科方法(与学术界和工业界)，以解决基本的生物学问题，应对新的治疗和社会挑战，并为人类健康带来好处。

Biomolecular interactions and characterisations form the basis of a plethora of research projects at King's, from fundamental investigations of molecular mechanisms to more applied research with medical and social impact. There is an increasing need to improve the precision and accuracy of these characterisations to achieve a detailed understanding of health and disease pathways and mechanisms, to facilitate the translation of this science towards outcomes that will benefit society. One of the key techniques used for such investigations is isothermal titration calorimetry (ITC), which provides a universal approach to study in detail how molecules are able to interact with one another, for example to understand which potential drug is able to block its target more efficiently, how bacteria develop resistance to antibiotics, or to explain the fundamental bases of life. For the many groups at King's, spread across four Faculties, there is a clear and urgent demand to improve upon the results that we can currently produce, and enable the characterisation and/or identification of new biochemical reactions or molecular assemblies that play a key role in a number of fields, including host-pathogen interactions, natural product biosynthesis, ageing, cardiovascular research, cancer, chemical biology and bioengineering, neurological disorders, signalling pathways, asthma and allergy. The instrumentation requested here holds promise of transforming the science of a wide user-base community at King's. King's is a leading international research institution across a range of biological disciplines, thus the potential for this investment of local provision of ITC instrumentation to add value is enormous. The ITC instrumentations will be part of the Wellcome Trust-supported Centre for Biomolecular Spectroscopy and will operate in synergy with other methodologies, integrating with other biophysical and structural biology methods and promoting exchanges with other in-house infrastructure and platforms (e.g. mass spectrometry, 'omics' platforms, imaging). The setting within the Centre will also facilitate usage by researchers from other academic institutions and/or industries, widening the breadth of the science that will be performed. Equipped with the latest ITC instrumentation, the Centre will contribute to the elucidation of molecular mechanisms of fundamental bioscience and permit state-of-the-art characterisation of biological therapeutics, to tackle strategic challenges in line with the BBSRC remit and priorities. The new instrument will strengthen the strategic mission of the Centre for Biomolecular Spectroscopy to deliver the highest quality data for internationally competitive research, train new generations of scientists in cutting edge methodologies, promote exchange of ideas and foster new interdisciplinary approaches (with academia and industries) for solving fundamental biological questions, addressing new therapeutic and societal challenges and providing benefits for human health.