Investigating versatile biomolecular interactions using microscale thermophoresis

这笔基础设施赠款加入了由国家科学研究和研究中心资助的7个研究所组成的研究小组，该小组使用核磁共振光谱、X射线结晶学和等温滴定热量计等生物物理手段来表征小分子(包括离子、糖、配体、片段…)之间的生物分子相互作用。、蛋白质和核酸。因此，这项应用旨在为重大和非常紧迫的升级提供资金，以巩固我们的基础设施，使用现代和灵敏的工具来定量描述生物分子相互作用。特别是，申请团队已经确定了Monolith NT.115微微仪器，它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。我们考虑的对现有基础设施(等温滴定量热仪-ITC)的主要改进在于购买了一种补充仪器，允许消耗最少的样品、更宽的检测范围(低至皮摩尔亲和力)、与原始样品分析的兼容性，以及对应用团队研究的各种生物分子(包括离子、小分子、多糖、核酸、膜蛋白、大分子络合物和脂泡)的广泛的样品通用性。所要求的Monolith NT.115微微仪器将是加拿大第一台此类仪器，为申请团队和高素质人员(HQP)提供研究生物分子相互作用的最新基础设施。该仪器将是7 NSERC研究计划的一项非常重要的资产，以继续开发新的方法，促进进一步的创新，并在生物科学领域提高~62HQP的生产率。所需的基础设施将加强我们的培训目标，为HQP提供熟练的动手培训机会，用尖端技术支持这些机会，并促进加拿大学术界和私营部门涌现出创新的领导者和富有生产力的劳动力。此外，这一申请还将为2018年授予的两个NSERC-Create培训计划计划提供相当大的投入，我们是蛋白质工程、定向进化和生物分子相互作用方面的教学和培训网站。

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.