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: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=637949
• 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的一些重大进展有助于提高我们对控制细胞生长和分化的分子机制的理解，确保损伤后的组织再生或引起导致癌症的异常细胞增殖。这项研究强调了细胞外基质（细胞外的非活体组织网络，作为特定蛋白质的储存库）的重要性，它在调节细胞间通讯中起着积极的作用。在过去的十年中，旨在模拟这种独特环境用于治疗应用的研究已经显示出巨大的前景;由于基于单克隆抗体的新疗法的设计，我们与癌症的斗争也得到了极大的改善。然而，与用于组织修复和再生的治疗性血管生成以及临床优化抗体生产相关的挑战仍然存在。考虑到这些需求，NSERC发现资助研究计划的中心目标是了解如何利用蛋白质之间相互作用的动力学调节来控制其生物活性，从而影响细胞行为和生物学结果。这将通过专注于被用作分子传感器和调制器的拴系分子的表征来实现。虽然这些工具本身具有多功能性，但将对它们进行调整，以应对两种相关应用的挑战：（i）开发可调表面和支架，允许在空间上控制蛋白质展示，（方向、密度、定位），时间（控释）和多因素（线索的组合）时尚和（ii）设计新的工具来解决单克隆抗体和相关受体的糖基化。这些系统将是非常感兴趣的体外细胞模型的设计和组织工程应用，如治疗性血管生成，以及建立定量的结构-活性关系，通过设计人工制品的自由测定。还将研究新的纯化方法的设计，以分离具有最佳治疗潜力的单克隆抗体。我们将产生的关于这些基本问题的知识和专有技术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，我们将培养优秀的学生在工程，生物化学和生物物理学之间的接口。这些学生将获得生物医学和生物制药公司高度追捧的基础知识和技术技能。