A versatile broad range microscale thermophoresis apparatus for the measurement of biomolecular interactions

分子相互作用是负责细胞活动的各个方面及其在药理干预中的调节的最基本的过程。微尺度热泳术（MST）是一种分子生物物理学技术，基于测量水合壳、电荷或分子大小的变化，因为这些变化会影响分子在微观温度梯度下的流动性。有了它，就有可能测量广泛的生物分子相互作用，从离子或片段结合到涉及多个伙伴的大型复合物的相互作用。由NanoTemper开发的免维护和低消耗成本的Monlith NT.115仪器是唯一可用的MST测量仪器，可用于量化亚nm至mM范围内的构象变化和结合亲和力，甚至使用复杂的混合物，如细胞裂解物。这台机器非常通用，不需要任何类型的复杂操作就能及时获得绑定亲和力。所要求的Monolith NT.115机器将是蒙特利尔大学的第一台此类机器，并允许在新成立的药理学和生理学系以及生物化学系的医学院内的大量研究人员推进研究项目和创造新的合作。本申请共同申请人的研究项目支持了一大批高素质人才的形成。特别是该仪器操作简单，可以在他们职业生涯的早期阶段将HQP引入到有形且成果丰富的项目中，这些项目将激发他们在生物分子相互作用测量方面继续发展职业的兴趣，例如着眼于制药应用。HQP获得MST等新技术也为这些HQP提供了市场竞争优势，这不仅有利于共同申请人的现有研究项目，而且可能在未来转化为加拿大知识和创新经济的红利。

Molecular interactions are the most basic processes responsible for all aspects of cellular activities and their modulation in pharmacological interventions. Microscale thermophoresis (MST) is a molecular biophysics technique based on the measurement of changes in the hydration shell, charge or size of molecules as these affect their mobility when subjected to microscopic temperature gradients. With this, it is possible to measure a wide range of biomolecular interactions, from ion or fragment binding to interactions of large complexes involving multiple partners. The maintenance-free and low consumable costs Monlith NT.115 apparatus developed by NanoTemper is the only available instrument for MST measurements and can be used to quantify conformational changes and binding affinities in the sub-nM to mM range using even complex mixtures such as cell lysates. This machine is extremely versatile and does not require any type of complex manipulations to obtain binding affinities in a timely manner. The requested Monolith NT.115 machine would be the first of its kind at the Université de Montreal and permit the advancement of the research programs and the creation of novel collaborations of a large number of researchers within the faculty of medicine in the newly formed department of pharmacology and physiology as well as in the department of biochemistry. The research programs of the co-applicants in this application support the formation of a large number of highly qualified personnel. The simplicity of manipulation with this instrument in particular make it possible introduce HQP at a very early stage in their careers to tangible and result-rich projects that will stimulate their interest in continuing developing their careers around the measurement of biomolecular interactions, for example with an eye towards pharmaceutical applications. The access of HQP to a new technology such as MST also offers a marketplace competitive edge for these HQPs that will benefit not only the existing research programs of the co-applicants but may also translate in the future into dividends to the Canadian knowledge and innovation economy.