NMR research

Funded PhD Projects

The following PhD projects come with funding (at the time of writing) to cover tutition fees and living expenses. Please note that they may not be available to students from outside the UK or the European Union. We strive to keep this page up to date, but please contact the supervisor of any PhD opportunity you wish to apply for. They will be able to provide current information on any funding restrictions. A more extensive list of projects, both with and without funding, is available.

Apply online

Oxidation-sensitive materials for targeting inflammation

Supervisor: Dr Seb Spain

PhD studentship in oxidation-sensitive materials for targeting inflammation

This project forms part of a larger programme that aims to develop a range of oxidation-sensitive materials for targeting the inflammatory environment that characterises certain chronic immune diseases such as rheumatoid arthritis and multiple sclerosis. The project will involve synthesis of a range of oxidation-sensitive polymerisation initiators, chain transfer agents and monomers, and the application of these to the synthesis of branched polymers with oxidation-sensitive localised in different places. Materials will be analysed with respect to their oxidation-sensitive behaviour via a range of techniques including electron microscopy and small angle X-ray scattering. Candidate materials will progress to biological screening for toxicity and cellular uptake.
This project will suit a candidate who wishes to develop an interdisciplinary skill set including organic chemistry, soft matter analysis, and in vitro biological techniques.

Further Details

The proposed start date for this studentship is September/October 2018. For further details or informal enquiries, please contact Dr Seb Spain via email s.g.spain@sheffield.ac.uk.

Funding

The funding includes a stipend at RCUK level and tuition fees for a UK student.

Person Specification

The candidate needs
• an undergraduate degree in Chemistry (minimum of 2:1 MChem or equivalent).
• research experience in either synthetic organic or polymer chemistry.
• excellent communication skills and the ability to work in a multidisciplinary team.

About the Spain Lab

The Spain Lab, based in the Department of Chemistry, University of Sheffield was started in 2014 and is led by Dr Seb Spain. The research team currently comprises 11 PhD students, 3 undergraduate students and 1 visiting postdoctoral researcher. Our research interests are broad and include advanced polymer synthesis including controlled radical polymerisations, self-assembled and responsive materials with applications in regenerative medicine, therapeutics and diagnostics. We are well equipped for both polymer synthesis and analysis including excellent chromatography and particle sizing instrumentation within the group as well as access to the Soft Matter Analytical Laboratory (SMALL) including our world-leading gallium source Small-Angle X-ray Scattering instrument in the Department of Chemistry.

Applying

You can apply for this studentship using our Postgraduate Online Application Form.

BBSRC DTP White Rose Studentship - Understanding how magnetotactic bacteria respond to magnetic fields

Supervisors: Dr S Staniland, Dr J Bergeron, Dr W Durham

Project Description

Some bacteria are magnetotactic, meaning that they have the unique capacity to sense and respond to a magnetic field. This means that we can manipulate the movement of these bacteria by simply exposing them to external magnetic fields. This capability is being exploited for biotechnological applications, such as turning bacteria into controllable drug delivery devices.

Magnetotactic bacteria sense the magnetic field through magnetite nanoparticles in their cells called magnetosomes, that acts like a compass needle across the length of the bacteria, causing them to align with external magnetic fields.

The molecular basis for motility in these bacteria is not well understood, and particularly how motility is affected by magnetic fields. We do know however that they move thanks to a flagellum, a corkscrew shaped appendage that generate thrust when it rotates. The aim of this project is to study the interplay between the magnetosome and the flagellum, using a range of approaches, covering biochemistry, structural biology, genetics, molecular biology, and microfluidics.

Funding Notes

4 year BBSRC studentship, under the BBSRC White Rose Mechanistic Biology DTP.

We welcome applications from students with first degrees in Biological, Chemical or Physical Sciences. For successful applicants, the studentships would provide funding for tuition fees and living stipend at the current Research Council UK rates (subject to eligibility) for 4 years. Please note that EU citizens must have lived in the UK for at least 3 years to be eligible for full support.

Applicants should have or expect to achieve an undergraduate honours degree at 2.1 or higher in a relevant field.

Applying

You can apply for this studentship using our Postgraduate Online Application Form.

The deadline for applications is Friday 5th January 2018.

BBSRC PhD Studentship: Analysis of neuronal kinesin-1 activation dynamics in response to cargo binding

Supervisors: Dr Alison Twelvetrees (Dept of Neuroscience, Sheffield), Dr Tim Craggs (Dept of Chemistry, Sheffield), Prof Michelle Peckham (Astbury Centre, Leeds)

We are recruiting a PhD student to work on an interdisciplinary project studying kinesin activation in the context of axonal transport and neurodegeneration. This project uses advanced single molecule imaging, biochemistry, and neuronal cell biology techniques to reveal fundamental insights into motor protein regulation and axonal transport, with translational outcomes for neurodegenerative diseases.

You will learn:

  • advanced microscopy & single molecule imaging
  • neuronal cell culture & live cell imaging
  • protein expression, labelling & purification

There is further potential to develop super-res (PALM/STORM; iSIM) and cryo-EM aspects to the project.

The successful applicant will be based in the Sheffield Institute for Translational Neuroscience, whilst working closely with all three labs involved. You will be supervised by Dr Alison Twelvetrees (Department of Neuroscience, Sheffield), Dr Tim Craggs (Department of Chemistry, Sheffield) and Prof Michelle Peckham (Astbury Centre, Leeds).

Creative individuals with an eye for detail are encouraged to apply. As an interdisciplinary project, applications from people from a diverse range of scientific backgrounds are welcomed, e.g. cell biology, biophysics, neuroscience, biochemistry, chemistry, structural biology, biomedical sciences.
Funding Notes

This is a BBSRC White Rose Doctoral Training Partnership PhD studentship fully funded for 4 years and covers:

  1. an annual tax-free stipend at the standard Research Council rate
  2. research costs
  3. tuition fees at the UK/EU rate.

Applying

Interested applicants should contact Dr Twelvetrees in the first instance to discuss the project: a.twelvetrees@sheffield.ac.uk.

Application Deadline

7th January 2018.

Further Information

twelvetreeslab.co.uk/join

craggs-lab.com

contractility.org

whiterose-mechanisticbiology-dtp.ac.uk

Mechanistic Biology of FAN1

Supervisors: Prof Jane Grasby, Dr David Williams, Dr Tim Craggs

Studentship Available for 17-18 with the White Rose Doctoral Training Programme in Mechanistic Biology

Applications are invited for a BBSRC funded White Rose Doctoral Training Programme Studentship to study the recently discovered 5’-nuclease FAN1. The FAN1 protein plays vital roles in the repair of cross-linked DNA, but how FAN1 functions is currently unclear. This project will study the mechanism for FAN1 using a combination of steady and pre-steady state enzyme kinetics, oligonucleotide chemistry and biophysical techniques such as fluorescence (FRET). The student will join a vibrant and world-leading research grouping within the Centre for Chemical Biology within the Krebs Institute for Mechanistic Biology. The four year BBSRC funded student will be able to access to a full range of career development and training opportunities via the White Rose Mechanistic Biology DTP.

Eligibility

Candidates will have at least a 2.1 degree or equivalent in Chemistry, Biochemistry or a related discipline and will receive a tax free stipend (currently £14, 553 pa) for four years, funds for research costs and tuition fees. There are language requirements for international students.

Further Details

Further Details can be obtained by contacting Prof Grasby (j.a.grasby@sheffield.ac.uk).

Applying

Applications to be received via the PGR portal with a deadline of 12th January 2018.

Selection Process

Shortlisting will take place as soon as possible after the closing date and successful applicants will be notified promptly. Shortlisted applicants will be invited for an interview to take place at the University of Sheffield, video interviews can be arranged for international applicants.

Screening of chemical libraries using iPS models for investigating the role of prion protein in Alzheimer’s disease

Background

AD has been identified as a protein misfolding disease (proteopathy). The disease is caused by accumulation of two major amyloids: a rounded “amyloid plaque” outside cells and “neurofibrillary tangles” inside cells. A number of theories have been developed to describe the cause and characteristics of AD although the exact cause is still not fully understood.1,2,3,4,5

Recently, it has been reported that cellular prion protein, PrPC, binds to Aβ1-42 oligomer and inhibits the long-term potentiation (LTP) in mice.6 Antibodies targeting the 94-104 region in PrPC blocks the inhibition of LTP triggered by soluble Aβ1-42 oligomer.7,8 PrPC has also been reported to affect the formation of the Aβ oligomers by modulating the function of β-secretase (BACE-1).9
Several lines of research has pointed to the nature of amyloid formation in AD having some synergies with prion formation in TSE (transmissible spongiform encaphlopathy, a family of fatal neurodegenerative diseases caused by conformational change of soluble prion protein, PrPC, into its insoluble counterpart, PrPSc, including scrapie in goats, mad cow disease in cattle and CJD in human). Although fundamental differences between these two diseases exist, the prion hypothesis10 articulates that the amyloidosis process of Aβ and Tau could well be prion-like. This is because it is suggested that the amyloid plaques such as Aβ and Tau, are formed via seeding of oligomers; and amyloidosis in one cell can trigger the nearby cells within tissue/organs to form plaques despite of the fact that AD is not transmissible from individual to individual.

Suggested role of prion protein in Alzheimer's disease

Fig. 1 Suggested role of prion protein, PrPc, in Alzheimer's disease. PrPc binds, regulates activity of BACE in cleavage of amyloid precursor protein (APP); PrPc acts as receptor for Aβ dimer. PrPc forms a complex with Fyn (probably with the help of Cav-1); and the complex regulates Tau hyperphosphoration, hence Tangle formation.

The close relationship amongst PrPC, Aβ and Tau was unveiled in recently studies. It was found that PrPC is enriched in postsynaptic densities, and the Aβ-PrPC interaction leads to activation of the Src tyrosine kinase Fyn and neuronal demise.11 Aβ engagement of PrPC-Fyn signalling yielded phosphorylation of the NR2B subunit of NMDARs. Fyn can mediate Aβ/Tau-induced toxicity.12 New evidence has showed that soluble Aβ and the Aβ1-42 dimer in particular can bind to PrPC at neuronal dendritic spines where it forms a quadruple complex with Fyn via Cav-1. This results in the activation of the Fyn kinase, which in turn triggers aberrant missorting and hyperphosphorylation of Tau, hence tangle formation.13,14 (Figure 1)

Henceforth, PrPC seems to be an important piece of the jigsaw in the AD landscape. Together with the amyloid and Tau theory, it could provide solutions to some unsolved questions in AD aetiology. Understanding the role PrPC in AD is extremely important and could shine lights on developing new diagnostics and drugs to combat AD.

Aims and Objectives

The aims of the project are:
• Develop and optimise iPS cellular model from epithelium cells from healthy and Alzheimer patient
• Study the interaction between PrPC and its interacting partners such as A, mGlu5, and NMDAR etc.
• Screen chemical libraries for compounds interfering the interactions
• Investigate the mode-of-action of initial hits

Project Plan

Year 1 - Develop and optimise iPS cellular model from epithelium cells from healthy and Alzheimer patient

Epithelium cells from healthy and Alzheimer patients will be reprogrammed and then differentiated into young neurons and cortical neurons and level of expression of PrPC and its interacting partners will be assessed using Western blotting and ICC and flow cytometry.

Year 2 - Study the interaction between PrPC and its interacting partners such as A, mGlu5, and NMDAR etc; screen chemical libraries for compounds interfering the interactions

Pairwise interaction studies between PrPC and its interacting partners will be carried out using doubly labelled fluorescence tags and the ability of small molecules in interfering such interactions will be assess. Hit compounds will be selected for further studies.

Year 3 - Investigate the mode-of-action of initial hits

The mode-of-action of selected hits will be thoroughly studied using a range of techniques such as RNAi screening and pull-down assays.

For more information

For more information, please contact Prof Beining Chen via email (b.chen@sheffield.ac.uk). To apply online for this studentship, click here.

References

1Braak, H ; Braak, E ; 1991. Acta Neuropathlogia, 82(4): 239-259;
2Bachmeier, C.; Paris, D.; Beaulieu-Abdelahad, D. et al. 2013, Neurodegen. Dis. 11(1): 13-21;
3Suh, Y.H.; Checler, F. 2002. Pharmcological Reviews. 3: 469-525;
4Hardy, J.; Allsop, D. 1991. Trends in Pharm. Sci. 12(10): 383-388;
5Um, J.W; Nygaard, H. B.; & Stephen M Strittmatter, S. M.; Nature NeuroSci. 2012, 15(9):1227-1235.;
6Larson, M.; Sherman, M. A.; Amar, F.; & Lesne, S.E. J. 2012. NeuroSci. 32(47): 16857-16871
7Benilova, I.; Karran, E.; & Bart De Strooper, B. D. Nature NeuroSci. 2012, 15(3): 349-357.;
8Sisodia, S.S.; St George-Hyslop, P.H. 2002. Nature Reviews Neuroscience. 3(4): 281-290.
9Esler, W.P; Wolfe, M.S. 2001. Science, 293(5534): 1449-1454;
10Griffiths, H. H and Hooper, N. M. et al. (2011) J. Biol.Chem. 286(38): 33489-33500.;
11Freir, D.B.; Nicoll, A.J.; Klyubin, I., Panico, S. & Collinge, J. 2011. Nat Commun 2:336.;
12Ittner, L.M.; Ke, Y.D; & Götz, J. et al. 2010. Cell 142:387–397.;
13Walsh, D.M.; Klyubin, I.; Selkoe, D.J. et al. 2002. Nature 416:535–539.;
14Williamson, R.; Scales, T.; & Anderton, B.H, 2002. J Neurosci 22:10–20.