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学干预中的调节的最基本过程。微尺度热泳（MST）是一种分子生物物理学技术，其基于测量分子的水化壳、电荷或大小的变化，因为这些变化在经受微观温度梯度时影响它们的流动性。有了这个，它可以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合作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，可用于使用甚至复杂的混合物（如细胞裂解物）在亚nM至mM范围内定量构象变化和结合亲和力。这台机器是非常通用的，不需要任何类型的复杂操作，以获得及时的结合亲和力。所要求的Monolith NT.115机器将是蒙特利尔大学同类机器中的第一台，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推进研究计划和创造大量研究人员的新颖合作。本申请中共同申请人的研究计划支持了大量高素质人才的形成。特别是这种仪器操作的简单性使得HQP能够在职业生涯的早期阶段引入有形和成果丰富的项目，这将激发他们继续围绕生物分子相互作用测量发展职业生涯的兴趣，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计划，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.