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Protein structure, function and analysis in biofluids using ultrafast spectroscopy


Department of Chemistry

York United Kingdom Physical Chemistry

About the Project

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 pharmaceutical and biomedical sectors.

Objectives

This PhD project will be part of a multidisciplinary team developing 2D-IR for biomedical applications. Working alongside chemists, biomedical spectroscopists and physicists you 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, you will develop our understanding of how the physiological environment of the body affects protein structure and dynamics and influences processes such as drug binding.

Experimental Approach

The team based at York has developed the method of ultrafast 2D-IR spectroscopy over the last 14 years, progressing from simple molecules in solution to understanding the structure, dynamics and intermolecular interactions of biological molecules (proteins and DNA) in real time. The successful candidate will join the most recent focus of this development process, using 2D-IR to understand how biological molecules behave in physiological environments. You will develop our knowledge of how protein spectroscopy in water and biofluids differs from the non-natural deuterated solutions typically used for IR spectroscopy and this will combine with parallel projects developing sample delivery systems and nanofabricated sample cells for rapid measurements to drive 2D-IR towards applications in biomedical diagnostics and drug design. The work will combine use of spectrometers located at the University of York with experimental visits to the Rutherford Appleton Laboratory, where we collaborate to develop 2D-IR on world-leading laser systems.

Novelty

The group led by Neil Hunt is the only one worldwide developing 2D-IR for biomedical analysis and we have recently published the first papers reporting this method. This project will carry out the first systematic study of protein structure, dynamics and intermolecular interactions in a physiological liquid, showing how proteins behave in their natural environment for the first time.

Training

The successful candidate will join a multidisciplinary team and training and post-doctoral support will be given in all aspects of the project, from biological sample handling to ultrafast laser spectroscopy and data analysis. No previous experience is necessary, but the project will suit candidates with an interest in physical chemistry, chemical physics, spectroscopy, or applications of lasers. A keen interest in multidisciplinary research, to become part of a team and a willingness to learn new skills are essential.

All Chemistry research students have access to our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills: https://www.york.ac.uk/chemistry/postgraduate/idtc/  

The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. The Department strives to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel: https://www.york.ac.uk/chemistry/ed/.

For more information about the project, click on the supervisor's name above to email the supervisor. For more information about the application process or funding, please click on email institution

This PhD will formally start on 1 October 2021. Induction activities will start on 27 September.

To apply for this project, submit an online PhD in Chemistry application: https://www.york.ac.uk/study/postgraduate/courses/apply?course=DRPCHESCHE3


Funding Notes

This studentship is fully funded for 3.5 years by an Engineering and Physical Sciences Research Council (EPSRC) Doctoral Training Partnership studentship and covers: (i) a tax-free annual stipend at the standard Research Council rate (£15,609 for 2021 entry), (ii) research costs, and (iii) tuition fees at the home or overseas rate.
Candidates of any nationality are welcome to apply and up to 30% of EPSRC DTP studentships will be awarded to international students (including those from the EU).
See guidance for further details: View Website
Not all projects will be funded; candidates will be appointed via a competitive process.

References

Candidate selection process:
• You should hold or expect to receive at least an upper second class degree (or equivalent https://www.york.ac.uk/study/international/your-country/) in chemistry or a chemical sciences related subject
• Applicants should submit a PhD application to the University of York by 15 April 2021. Please note you will be unable to submit an application 6-12 April due to essential maintenance of the application system
• Supervisors may contact candidates either by email, telephone or web-chat
• Supervisors can nominate up to 2 candidates to be interviewed for the project
• The interview panel will shortlist candidates for interview from all those nominated
• Shortlisted candidates will be invited to a remote panel interview on 18 or 19 May
• The awarding committee will award studentships following the panel interviews
• Candidates will be notified of the outcome of the panel’s decision by email

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