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University of Kent funded PhD in the School of Biosciences

The studentship will pay an annual stipend at the UK Research Council rate of £14,553 (rate for 2017/2018) and cover tuition fees at the rate for UK/ EU students. International applicants must make provision to meet the difference between Home and International fees. The studentship is offered as a Graduate Teaching Assistantship which requires the student to carry out a number of hours of teaching / teaching support duties in the School of Biosciences.

The School of Biosciences is pleased to announce funding for a 3 year PhD studentship to start in September 2017.

Project: Mapping the molecular mechanisms of chaperone-amyloid interaction.

Supervisor/s: Dr Wei-Feng Xue and Professor Mick Tuite, Kent Fungal Group, School of Biosciences

BACKGROUND:
How do molecular chaperones interact and fragment amyloid fibrils in cells? This is the central question that this PhD project will address. Amyloid is an aggregated state of proteins associated with a number of devastating human disorders, for example Alzheimer’s disease (AD), Parkinson's disease (PD), type 2 diabetes, and transmissible spongiform encephalopathies (TSEs). Amyloid diseases account for increasing medical and social importance, for example, more than half million people are suffering from AD in the UK alone, and PD affects about 1% of the population over the age of 60.
Until recently, only the TSEs were believed to be infectious diseases via transmissible amyloid particles known as prions and typified by Creutzfeldt Jakob Disease in humans. New data are emerging, which suggest that the amyloid aggregates previously thought to be non-infectious (for example Abeta amyloid associated with AD), can propagate the disease state in the infected individual. How this propagation proceeds in vivo in disease is not known. It is this question we seek to answer in this project.

PROJECT OUTLINE:
The supervisors, Wei-Feng Xue and Mick Tuite are both core members of the Kent Fungal Group (KFG), running well-funded and well-equipped labs in the School of Biosciences at the University of Kent. They have long standing research interest in the formation of amyloid and the propagation of prions. Previous work by WFX and MFT has independently highlighted a fibril fragmentation mechanism of how transmission of amyloid might occur. WFX has developed a quantitative model of fibril fragmentation that explains the formation of small propagation competent seeds from large amyloid fibrils, and has developed AFM imaging methods to study these events and seeds. MFT has long standing expertise in the yeast prion protein Sup35, and how the amyloid form of Sup35 can propagate in vivo in yeast to confer the heritable [PSI+] phenotype through the enzymatic fragmentation action of the chaperone machinery involving Hsp104, 70 and 40.
The project will be centred on the following objectives.

  1. To develop methods to express and purify chaperones with known amyloid fragmentation activities.
  2. To develop imaging methods to quantify individual fibril particles during fibril fragmentation in the absence and presence of the purified chaperone proteins.
  3. To delineate the molecular mechanism of enzymatic Sup35NM amyloid fibril fragmentation. Sup35NM is a well-established yeast prion amyloid model system in our research programmes.

The candidate will have the access to a range of protein biochemistry, microscopy, molecular and cell biology, computational modelling, and biophysical methods, including the state-of-the-art high-resolution atomic force and super resolution microscopy imaging equipment in the Biosciences imaging facility. This project will provide the candidate with a broad multidisciplinary scientific training.  
The successful candidate will be based in Wei-Feng Xue’s and Mick Tuite’s research groups in the Kent Fungal Group (KFG) in School of Biosciences at the University of Kent (Canterbury campus).

Criteria

The successful candidate is expected to be a highly motivated student with an interest in multidisciplinary research. He/she will be expected to have a degree at 2(i) or higher in Biochemistry, Biophysics, Biotechnology, Bioengineering, Biology, Biomedical Science, Chemistry or Chemical Engineering.

How to apply

Please submit an on-line application for the PhD Biochemistry via the University application page. Please]enter the project title as the proposed research topic and Dr Wei-Feng Xue as the supervisor. For the research proposal please enter "as advertised". Please include a cv and a covering letter.

Informal enquiries can be addressed to Wei-Feng Xue (W.F.Xue@kent.ac.uk) or Mick Tuite (M.F.Tuite@kent.ac.uk).


Deadline

The deadline for applications for this scholarship has passed.


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