new agents for the visualization of biochemistry in live cells

用于活细胞生物化学可视化的新试剂

• 批准号: 288338-2007
• 负责人: Campbell, Robert
• 金额: $ 4.01万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=364000
• 关键词: new; agents; visualization; biochemistry; live

Proteins are amazing molecular machines that are essential for Life as we know it. After a century of protein research, we now have a very good understanding of how proteins are able to carry out their vast array of functions. However, our understanding is not deep enough to allow us to rationally design new protein structures with functions not found in Nature. Thus, when we want to use proteins as benign 'tools' to benefit mankind, we are limited to what Nature has provided us. Fortunately, Nature has been generous and protein 'tools' are now taken for granted in many aspects of modern life, including household products (e.g. laundry detergent), medical diagnostics (e.g. blood glucose sensors to control diabetes), and biotechnology (e.g. PCR).     It is in this last category that the green fluorescent protein (GFP) from jellyfish has found widespread utility. GFP has the unique (among proteins) ability to generate a visible wavelength fluorophore within its own 3-dimensional structure and thus can absorb blue light and reemit it as green light. In the past decade, this remarkable protein 'tool' has enabled many exciting advances in biological research because genetically inserting GFP into a living cell or tissue allows one to 'see' biological structures that would otherwise be undetectable.     My specific research interest is in expanding the 'toolkit' of proteins that are useful in basic biological research. For example, it is useful to have a wide selection of 'colors' of fluorescent proteins so that multiple biological structures can be 'visualized' simultaneously. We would also like to add a dynamic new dimension to fluorescent proteins and engineer them to be biosensors that change their fluorescence in response to specific biological events. Many of the potential applications of such biosensors lie in the realm of fundamental cell biology research. However, these technological advances will also be applicable to the areas of medical diagnostics, drug discovery, and advanced approaches for imaging and treatment of cancer.

蛋白质是我们所知的生命所必需的惊人的分子机器。经过世纪的蛋白质研究，我们现在对蛋白质如何能够执行其大量功能有了很好的了解。然而，我们的理解还不够深入，不足以让我们合理地设计新的蛋白质结构，其功能在自然界中没有发现。因此，当我们想使用蛋白质作为造福人类的良性“工具”时，我们仅限于大自然为我们提供的东西。幸运的是，大自然一直很慷慨，蛋白质“工具”现在在现代生活的许多方面都被认为是理所当然的，包括家用产品（例如洗衣粉），医疗诊断（例如控制糖尿病的血糖传感器）和生物技术（例如PCR）。 正是在这最后一类中，来自水母的绿色荧光蛋白（GFP）已经发现了广泛的用途。GFP具有在其自身的三维结构内产生可见波长荧光团的独特能力（在蛋白质中），因此可以吸收蓝光并将其重新发射为绿色光。在过去的十年中，这种非凡的蛋白质“工具”使生物学研究取得了许多令人兴奋的进展，因为将GFP基因插入活细胞或组织中可以让人们“看到”生物结构，否则无法检测到。 我的具体研究兴趣是扩大在基础生物学研究中有用的蛋白质的“工具包”。例如，具有荧光蛋白的“颜色”的广泛选择是有用的，使得可以同时“可视化”多个生物结构。我们还希望为荧光蛋白添加一个动态的新维度，并将其设计为生物传感器，以改变其荧光以响应特定的生物事件。这种生物传感器的许多潜在应用在于基础细胞生物学研究领域。然而，这些技术进步也将适用于医学诊断、药物发现以及癌症成像和治疗的先进方法。