Protein structure, function and analysis in biofluids using ultrafast spectroscopy

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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.