MRes/PhD Studentship: Investigating copper homeostasis in a human fungal pathogen
- Reference Code: CB068
Details:
Name of the supervisors
Professor C Dennison , Institute for Cell and Molecular Biosciences
Dr J Rutherford , Institute for Cell and Molecular Biosciences
Dr KJ Waldron , Institute for Cell and Molecular Biosciences
Sponsor
John William Luccock and Ernest Jeffcock Research Studentship
Duration of the award
Either 3 year PhD or 4 year integrated MRes plus PhD
Project description
Cryptococcus neoformans is an opportunist fungal pathogen that causes disease in the immuno-compromised, such as patients with AIDS, and is increasingly recognised as an emerging infection of immuno-competent individuals. C. neoformans has evolved numerous traits that allow it to survive within the human body, many of which rely on metals, and particularly copper. Due to its potential toxicity copper is trafficked via pathways to different cellular destinations in a eukaryote such as C. neoformans. The investigation of copper homeostasis in a pathogenic fungus will therefore not only enable the basic principles of copper homeostasis to be uncovered but will also provide insight into designing therapies that target copper as a way to treat cryptococcosis.
The copper proteome of C. neoformans will be studied using a combined in vitro/in vivo approach including metalloproteomic approaches (1). The influence of copper availability and the anti-cancer compound cisplatin, which is known to interfere with copper homeostasis, on copper distribution in C. neoformans will be determined. The copper affinities of target proteins and metallochaperones will be determined in vitro using competition titrations with chromophoric ligands (2). Along with the abundance of all copper proteins these data will demonstrate if thermodynamics dictate cellular copper trafficking. Insight will also be obtained into whether cross-talk between trafficking pathways occurs and the nature of the copper pools from which the different pathways acquire copper.
The student will obtain training in a range of areas including metalloprotein purification and characterisation, metal affinity determinations, yeast genetics and molecular biology techniques.
(1) S. Tottey, K. J. Waldron, S. J. Firbank, B. Reale, C. Bessant, K. Sato, T. R. Cheek, J. Gray, M. J. Banfield, C. Dennison and N. J. Robinson, Nature 2008, 455, 1138-1142.
(2) A. Badarau and C. Dennison, Proc. Natl. Acad. Sci. USA 2011, 108, 13007-13012.
Value of the Award and Eligibility
The award covers University fees at the Home/EU rate and a stipend matched to the minimum Research Council recommended stipend of £13,590 (2011/12).
Person Specification
Applicants should have, or be expecting to achieve, a first or very good upper second class degree in Biological Chemistry, Biochemistry or a related subject.
How to Apply
You must apply through the University's online postgraduate application form inserting the reference number CB068 and selecting 'Master of Research/Doctor of Philosophy (Medical Sciences) - Cell and Molecular Biosciences' as the programme of study. Only mandatory fields need to be completed (no personal statement required) and a covering letter, CV and (if English is not your first language) a copy of your English language qualifications must be attached. The covering letter must state the title of the studentship, quote the reference number CB068 and state how your interests and experience relate to the project.
You should also send your covering letter and CV to:-
Professor Chris Dennison
Institute for Cell and Molecular Biosciences
Cookson Building
Medical School
Newcastle University
Newcastle upon Tyne
NE2 4HH
Preferably by email to christopher.dennison@ncl.ac.uk
Closing date for applications
Prompt application is advised as this post is only available until a suitable candidate is appointed.
Further Information
For further details, please contact Professor Chris Dennison, christopher.dennison@ncl.ac.uk , +44 (0)191 222 7127