Protein structure, function and analysis in biofluids using ultrafast spectroscopy

使用超快光谱分析生物流体中的蛋白质结构、功能和分析

• 批准号: 2599265
• 金额: --
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2599265
• 关键词: Protein; structure; function; analysis; biofluids

Background: Biofluids, such as blood serum (blood with the red blood cells removed), provide an important monitor of a person's health because they contain a complex mixture of proteins, sugars, phospholipids and nucleic acids that gives a molecular fingerprint of metabolism. Measuring changes in the molecular make-up of biofluids offers an easily accessible, informative way to monitor health and detect disease.We have recently shown that ultrafast 2D-IR spectroscopy is a powerful tool for blood serum analysis. Using a sequence of ultrashort infrared laser pulses, 2D-IR can suppress strong water absorptions and pick out signals due to proteins in biofluids like finding needles in a haystack (Hume et al Chemical Science 10, 6448-6456 (2019)). By spreading an infrared spectrum over a second spectral dimension (like 2D-NMR) 2D-IR also gives a 2D 'map' that is extremely sensitive to protein structure, rapid changes in structure (structural dynamics) and intermolecular interactions.In this project we will explore the structure, dynamics and function of proteins in blood serum. By understanding how the 2D-IR map can be used to uniquely identify a protein of interest in a mixture, before determining how the complex molecular environment of a biofluid affects its structure and dynamics, this PhD will develop exciting new insights and measurement methods relevant to the chemical, pharmaceutical and biomedical sectors.ObjectivesThis PhD project will be part of a multidisciplinary study developing 2D-IR for biomedical applications, including chemists, biomedical spectroscopists and physicists. The project will measure the 2D-IR spectra of a range of key blood serum proteins and develop methods to measure their concentrations in real-world samples. Using the ability of 2D-IR to probe protein dynamics in water for the first time, the project will develop our understanding of how the physiological environment of the body affects protein structure and dynamics and influences processes such as drug binding.

背景：生物体液，如血清(去除红细胞的血液)，是人体健康的重要监测器，因为它们含有蛋白质、糖、磷脂和核酸的复杂混合物，提供了新陈代谢的分子指纹。测量生物体液分子组成的变化为监测健康和检测疾病提供了一种容易获得的、信息丰富的方法。我们最近已经表明，超快2D-IR光谱是血清分析的有力工具。使用一系列超短红外激光脉冲，2D-IR可以抑制强烈的水吸收并识别由于生物液中的蛋白质而产生的信号，就像大海捞针一样(Hume等人的化学科学10,6448-6456(2019))。通过将红外光谱扩展到第二个光谱维度(如2D-核磁共振)，2D-IR还提供了对蛋白质结构、结构快速变化(结构动力学)和分子间相互作用极其敏感的2D‘MAP’。在这个项目中，我们将探索血清中蛋白质的结构、动力学和功能。在确定生物流体的复杂分子环境如何影响其结构和动力学之前，通过了解如何使用2D-IR图来唯一地识别混合物中的感兴趣的蛋白质，本博士将开发与化学、制药和生物医学部门相关的令人兴奋的新见解和测量方法。目标本博士项目将是为包括化学家、生物医学光谱仪和物理学家在内的生物医学应用开发2D-IR的多学科研究的一部分。该项目将测量一系列关键血清蛋白质的2D-IR光谱，并开发测量现实世界样本中它们浓度的方法。利用2D-IR首次探测水中蛋白质动力学的能力，该项目将加深我们对身体生理环境如何影响蛋白质结构和动力学以及影响药物结合等过程的理解。