Surface Bioconjugation for Regenerative Medicine and Biosensing Applications

用于再生医学和生物传感应用的表面生物共轭

• 批准号: RGPIN-2015-04960
• 负责人: DeCrescenzo, Gregory
• 金额: $ 2.19万
• 依托单位: École Polytechnique de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=648800
• 关键词: Surface; Bioconjugation; Regenerative; Medicine; Biosensing

A number of recent major inroads in biochemistry, cellular biology and medicine have helped improve our understanding of the molecular mechanisms governing cell growth and differentiation, assuring tissue regeneration after injury or causing abnormal cell proliferation leading to cancer. This research has underscored the importance of the extracellular matrix (a network of non-living tissue outside the cell that acts as a reservoir of specific proteins), which plays an active role in modulating intercellular communication. During the last decade, research aiming to mimic this unique environment for therapeutic applications has shown great promise; our fight against cancer has also greatly improved thanks to the design of new therapies based on monoclonal antibodies. However, challenges associated with therapeutic angiogenesis for tissue repair and regeneration, as well as with optimized antibody production for the clinic, still remain. Keeping these needs in mind, the central objective of this NSERC Discovery Grant Research Program is to understand how the modulation of the dynamics of the interactions between proteins may be utilized to control their biological activity, and thereby affect cell behaviour and biological outcomes. This will be achieved by focusing on the characterization of tethered molecules to be utilized as molecular sensors and modulators. While inherently versatile, the tools to be developed will be adapted to meet the challenges of two applications of interest: (i) the development of tuneable surfaces and scaffolds allowing for the control of protein display in a spatial (orientation, density, localization), temporal (controlled release) and multifactorial (combination of cues) fashion and (ii) the design of new tools to tackle the glycosylation of monoclonal antibodies and related receptors. These systems will be of great interest for the design of in vitro cellular models and in tissue engineering applications such as therapeutic angiogenesis as well as to establish quantitative structure-activity relationships by designing artefact-free assays. The design of new purification approaches to isolate a monoclonal antibody bearing the best therapeutic potential will also be investigated. The knowledge and know-how we will generate about these fundamental issues have the potential to profoundly impact the biomedical and biopharmaceutical industries. Furthermore, throughout this Research Program we will train outstanding students at the interface between engineering, biochemistry and biophysics. These students will acquire fundamental knowledge and technical skills highly sought after by biomedical and biopharmaceutical companies. ********

最近在生物化学，细胞生物学和医学方面有许多重大侵害有助于我们对控制细胞生长和分化的分子机制的理解，从而确保受伤后的组织再生或导致异常细胞增殖导致癌症。这项研究强调了细胞外基质（细胞外的非生存组织网络，充当特定蛋白质的储层），该网络在调节细胞间通信中起着积极作用。在过去的十年中，研究旨在模仿这种独特的治疗应用环境的研究表现出了很大的希望。由于基于单克隆抗体的新疗法的设计，我们对癌症的斗争也大大改善。然而，与治疗性血管生成有关组织修复和再生以及诊所优化抗体的挑战仍然存在。考虑到这些需求，该NSERC发现赠款研究计划的核心目标是了解如何利用蛋白质之间相互作用的动态来控制其生物学活性，从而影响细胞行为和生物学结果。这将通过关注被用作分子传感器和调节剂的束缚分子的表征来实现。 While inherently versatile, the tools to be developed will be adapted to meet the challenges of two applications of Interest: (i) the development of tuneable surfaces and scaffolds allowing for the control of protein display in a spatial (orientation, density, localization), temporary (controlled release) and multifactorial (combination of cues) fashion and (ii) the design of new tools to tackle the glycosylation of monoclonal抗体和相关受体。这些系统对于设计体外细胞模型和组织工程应用（例如治疗性血管生成）以及通过设计无伪影测定的定量结构 - 活性关系将引起极大的兴趣。还将投资具有最佳治疗潜力的单克隆抗体的新纯化方法的设计。我们将对这些基本问题产生的知识和知识有可能深刻影响生物医学和生物制药行业。此外，在整个研究计划中，我们将在工程，生物化学和生物物理学之间的界面上培训出色的学生。这些学生将获得基本知识和技术技能，由生物医学和生物制药公司备受追捧。 *******