New Spectroscopic Tools for Characterising Glycan Structure

碳水化合物和糖广泛存在于包括人类在内的所有生命系统中，它们对维持我们的健康和营养非常重要。它们对英国的经济繁荣也很重要，因为碳水化合物是大多数食品和饮料的主要成分。我们开发新药物、新疗法、新材料或其他生物学科学进步的主要方式是了解分子的结构以及这种结构如何决定它们的稳定性和与其他分子的相互作用。这种方法支撑了过去50年来遗传学、医学、生物材料等领域的发展，主要是通过开发研究蛋白质和核酸结构的工具。我们对碳水化合物在生物学中的作用的理解比蛋白质差得多，不是因为碳水化合物比蛋白质更不常见，或者不参与关键的生理过程（它们显然是），而是因为结构生物学中使用的主要工具不容易适用于碳水化合物。这个长期存在的问题导致我们对大多数碳水化合物的行为或功能知之甚少。显然，为了更好地发展这种理解水平，我们需要新的工具来研究碳水化合物结构。对于这些工具来说，它们应该对大量的结构信息敏感，它们应该能够区分单个糖及其各种聚合物，它们应该能够提供碳水化合物的稳定性和相互作用，并且它们应该能够在各种条件下对所有或至少大多数碳水化合物进行所有这些。拉曼光谱满足所有这些要求，我们将开发这些基于激光的技术，用于研究溶液和凝聚相（通常发现大多数碳水化合物的两种生理条件）中的碳水化合物。实验拉曼技术和先进形式的数据分析将被用来建立一个互补的工具集，用于表征任何碳水化合物的结构，从最小的糖到最大的聚合物，以及它们的功能行为。我们已经开发了类似的工具来研究其他生物分子，我们的初步研究证实，这些工具将是非常有用的生物学家研究碳水化合物。该泵启动项目将为未来的发展和项目奠定坚实的基础，首先，生成用于解释碳水化合物数据的光谱库，其次，优化专业形式的数据分析，以了解与生理过程相关的碳水化合物聚合物结构变化的机制。新的工具产生新的科学，并最终在医学和工业中应用。我们将开发的拉曼光谱法的一个巨大优势是它们能够用于许多不同的问题，特别是它们收集凝聚相碳水化合物数据的能力，这与许多生物学例子相关，但不适合传统的糖生物学技术。因此，我们的项目将是设计一系列工具的重要和重要的第一步，这些工具将导致糖生物学，医学和农业的许多未来发展。

Carbohydrates and sugars are found widely in all living systems, including humans, and they are important for maintaining our health and nutrition. They are also important for the economic prosperity of the UK as carbohydrates are major components of most foods and beverages. A principal way in which we develop new medicines, therapies, materials or other scientific advances in biology is by understanding the structure of molecules and how this structure determines their stability and interactions with other molecules. This approach has underpinned the last 50 years of developments in genetics, medicines, biomaterials etc., mainly through development of the tools for studying the structure of proteins and nucleic acids. Our understanding of the roles of carbohydrates in biology is much poorer than that of proteins, not because carbohydrates are less common than proteins or aren't involved in critical physiological processes (they clearly are), but because the main tools used in structural biology aren't easily applicable to carbohydrates. This long standing problem has resulted in our knowing little about the behaviour or function of the great majority of carbohydrates. Obviously, in order to better develop this level of understanding we need new tools for studying carbohydrate structure. For these tools to be generally useful they should be sensitive to a large amount of structural information, they should be able to differentiate between individual sugars and their various polymers, they should be able to inform on the stability and interactions of carbohydrates, and they should be able to do all this for all, or at least most, carbohydrates under a wide range of conditions. Raman spectroscopies fulfil all of these requirements and we will develop these laser-based techniques for studying carbohydrates in both solutions and the condensed phase (the two physiological conditions in which most carbohydrates are normally found). Both experimental Raman techniques and advanced forms of data analysis will be utilised to set up a complementary tool set for characterising the structure of any carbohydrate, from the smallest sugar to the largest polymer, and their functional behaviour. We have already developed analogous tools for studying other biomolecules and our preliminary studies verify that these tools will be highly useful to biologists studying carbohydrates. This pump priming project will establish a solid foundation for future developments and projects by, firstly, generating a spectral library for interpretation of carbohydrate data and, secondly, optimising specialised forms of data analysis for understanding the mechanisms of structural changes in carbohydrate polymers relevant to physiological processes. New tools generate new science and, ultimately, applications in medicine and industry. A great advantage of the Raman spectroscopies that we will develop is their ability to be used on many different problems, and particularly their ability to collect data on carbohydrates in the condensed phase, which is relevant to many biological examples but is not amenable to conventional glycobiology techniques. Therefore, our project will be the vital and large first step in designing a range of tools that will lead to many future developments in glycobiology, medicine and agriculture.