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Somerville College Studentship for a DPhil in the Biomedical Sciences

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  • Full or part time
    Dr D Anthony
    Prof D Tyler
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Project description

We are looking for applicants who would like to undertake an imaging project using hyperpolarization. In recent years, the development of cardiac Magnetic Resonance Imaging (MRI) has provided a valuable new approach for the assessment of cardiac structure and function. However, despite the enormous technical developments that have taken place, MRI remains an inherently low sensitivity technique and the low signal levels obtained limit certain applications, e.g. multi-nuclear spectroscopy for the assessment of metabolism.

More recently, the development of a range of techniques, which can be gathered under the umbrella term of ‘hyperpolarization’, has offered potential solutions to this low sensitivity. Dynamic Nuclear Polarization (DNP-MR) is one such hyperpolarization method, which has been demonstrated to increase the sensitivity of MRI to detect metabolic tracers by more than 10,000-fold, thereby allowing in vivo cardiac substrate uptake and metabolism to be measured in real time and at repeated time-points during disease progression.

The DPhil student will aim to develop new imaging techniques and novel metabolic imaging probes to assess metabolism in the heart. These techniques will be applied and used to help us understand the mechanisms that control and regulate metabolism in the heart.

There is also an opportunity for the candidate to explore the application of hyperpolarized 29Si nanoparticles in animal models of neurological disease. Firstly, the optimal hyperpolarization protocol of Si-nanoparticles will be established. Secondly, to make the nanoparticles biologically useful, the particles will be modified/functionalized. Most silicon nanoparticles are composed from SiO2 and contain hydroxyl groups on their surface which will be used for these chemical modifications. Functionalization will be achieved by the addition of chemical entities that selectively target the activated brain endothelium. Finally, we will fill the functionalized nanoparticles with therapy to promote the degradation of aggregated proteins and test them in vivo. The project will allow the student to learn an array of techniques, including in vivo magnetic resonance imaging and hyperpolarization techniques, glycochemistry, and in vivo skills.

Funding Notes

We welcome applications from UK and EU applicants. The Studentship is provided by Somerville College Oxford and successful applicants will become members of Somerville College. The Studentship will cover all fees (University and College) and a stipend of £16,000 pa will be awarded. The interview date will be 25th or 26th February. Please apply by email and send (as one pdf) a cover letter, CV, two testimonials and indicate which project title is of interest to you.

References

Couch et al. Circulating endothelial cell-derived extracellular vesicles mediate the acute phase response and sickness behaviour associated with CNS inflammation. Sci Rep. 2017.
Perez-Balderas F, van Kasteren SI, Aljabali AA, et al. Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI. Nat Commun. 2017;8:14254. Published 2017 Feb 15. doi:10.1038/ncomms14254
Serpell CJ, Rutte RN, Geraki K, et al. Carbon nanotubes allow capture of krypton, barium and lead for multichannel biological X-ray fluorescence imaging. Nat Commun. 2016;7:13118. Published 2016 Oct 26. doi:10.1038/ncomms13118

Lewis AJ, Miller JJ, Lau AZ, Curtis MK, Rider OJ, Choudhury RP, Neubauer S, Cunningham CH, Carr CA, Tyler DJ. Non-Invasive Immuno-Metabolic Cardiac Inflammation Imaging Using Hyperpolarized Magnetic Resonance. Circ Res. 2018 Feb 12. PMID:29440071
Miller JJ, Lau AZ, Nielsen PM, McMullen-Klein G, Lewis AJ, Jespersen NR, Ball V, Gallagher FA, Carr CA, Laustsen C, Bøtker HE, Tyler DJ, Schroeder MA. Hyperpolarized [1,4-13C2]Fumarate Enables Magnetic Resonance-Based Imaging of Myocardial Necrosis. JACC Cardiovasc Imaging. 2017 Dec 8. PMID: 29248653
Lau AZ, Miller JJ, Robson MD, Tyler DJ. Simultaneous Assessment of Cardiac Metabolism and Perfusion Using Co-Polarized [1-13C]Pyruvate and 13C-Urea. Magn Reson Med. 2016 Jan 7. PMID: 26743440
Miller JJ, Lau AZ, Teh I, Schneider JE, Kinchesh P, Smart S, Ball V, Sibson NR, Tyler DJ. Robust and High Resolution Hyperpolarized Metabolic Imaging of the Rat Heart at 7T with 3D Spectral-Spatial EPI. Magn Reson Med. 2015 May 20. PMID: 25991606
Lau AZ, Miller JJ, Robson MD, Tyler DJ. Cardiac Perfusion Imaging Using Hyperpolarized 13C Urea Using Flow-Sensitizing Gradients. Magn Reson Med. 2015 May 20. PMID: 25991580

Araç D., Sträter N., Seiradake E. (2016) Understanding the Structural Basis of Adhesion GPCR Functions. In: Langenhan T., Schöneberg T. (eds) Adhesion G Protein-coupled Receptors. Handbook of Experimental Pharmacology, vol 234. Springer, Cham

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