Investigating versatile biomolecular interactions using microscale thermophoresis

该基础设施拨款将由INRS Institut Armand-Frappier（INRS-IAF）的7个NSERC资助的学院组成的研究团队结合在一起，使用NMR光谱学，X射线晶体学和等温滴定量热法等生物物理工具来表征小分子（包括离子，糖，配体，片段......），蛋白质和核酸之间的生物分子相互作用。因此，该申请旨在资助一项重大而紧迫的升级，以巩固我们的基础设施，并配备现代化的灵敏仪器，用于生物分子相互作用的定量表征。特别是，申请人团队已经确定了Monolith NT.115皮科仪器，该仪器满足了我们对多功能和多用途生物分子相互作用设备的所有基础设施需求。考虑对现有基础设施进行的主要改进等温滴定量热计（ITC）的优点在于获得了一种补充仪器，允许最小的样品消耗，更宽的检测范围，低至皮摩尔亲和力，与粗样品分析兼容，以及对应用团队研究的各种生物分子的广泛样品通用性，包括离子，小分子，多糖，核酸，膜蛋白、大分子复合物和脂质囊泡。所要求的Monolith NT.115皮科仪器将是加拿大第一台此类仪器，为申请人团队和高素质人员（HQP）提供最先进的生物分子相互作用研究基础设施。该仪器将是一个非常重要的资产，7 NSERC研究计划，继续开发新的方法，促进进一步的创新，并提高生产力的~62 HQP在生物科学。所要求的基础设施将加强我们的培训目标，为HQP提供熟练的实践培训机会，为他们提供尖端技术，并支持加拿大学术和私营部门的创新领导者和生产力。此外，该应用程序还将为2018年授予的两项NSERC-CREATE培训计划提供大量投入，我们是蛋白质工程，定向进化和生物分子相互作用的教学和培训网站。

This infrastructure grant joins together a research team composed of 7 NSERC-funded faculties at the INRS Institut Armand-Frappier (INRS-IAF) using biophysical tools such as NMR spectroscopy, X-ray crystallography and isothermal titration calorimetry to characterize biomolecular interactions between small molecules (including ions, sugars, ligands, fragments…), proteins, and nucleic acids. Accordingly, this application aims to finance a significant and very urgent upgrade to consolidate our infrastructure with a modern and sensitive instrument for the quantitative characterization of biomolecular interactions. In particular, the applicant team has identified the Monolith NT.115 pico instrument that meet all our infrastructure needs for a versatile and multi-purposed biomolecular interaction equipment. The key improvements considered over our existing infrastructure (isothermal titration calorimeter - ITC) consist in the acquisition of a complementary instrument allowing a minimal consumption of sample, a wider detection range down to picomolar affinities, compatibility with crude sample analysis, and a broad sample versatility toward the diverse biomolecules investigated by the application team, including ions, small molecules, polysaccharides, nucleic acids, membrane proteins, macromolecular complexes, and lipid vesicles. The requested Monolith NT.115 pico instrument would be the first of its kind in Canada, providing the applicant team and highly qualified personnel (HQP) with the most up-to-date infrastructure for the study of biomolecular interactions. The instrument will be a very important asset to 7 NSERC research program to continue developing new approaches, facilitate further innovation, and increase productivity of ~62 HQP in biological sciences. The requested infrastructure will enhance our training objectives to deliver proficient hands-on training opportunities to HQP, endorsing them with cutting-edge technology, and bolstering emergence of innovative leaders and productive workforce in academic and private sectors in Canada. In addition, this application will also provide considerable inputs toward two NSERC-CREATE training program initiatives awarded in 2018, for which we are a teaching and training site in protein engineering, directed evolution, and biomolecular interactions.