The Bloomsbury Colleges | PhD Studentships | Studentships 2011 | Structural and Functional Studies of the Hsp90-dependent Phosphatase PP5 in Plasmodium falciparum
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Structural And Functional Studies Of The Hsp90-Dependent Phosphatase PP5 In The Malaria Parasite Plasmodium Falciparum

Lead Supervisor: Cara Vaughan (Bbk)

Co-Supervisor: Johannes Dessens (LSHTM)

Malaria, transmitted by Plasmodia parasites, infects more than 300 million people worldwide, and is responsible for over 1 million deaths annually. However therapeutic intervention is currently limited by an increasing number of strains developing resistance to existing drugs, driving the search for new compounds with anti-malarial activity.

Heat shock proteins are molecular chaperones conserved throughout eukaryotes that promote proper folding and activation of proteins. They are abundant in Plasmodium falciparum (Pf), the most virulent parasite in humans, and are essential for the organism’s ability to adapt to the different environments the parasite encounters during its life cycle. As such they have become a recent target for anti-malarial chemotherapeutic development. At the forefront of these new targets is Hsp90, an ATPase that acts in cooperation with a plethora of accessory proteins (cochaperones) to allow activation of substrate proteins.

This project will involve gaining structural and functional insight into one such cochaperone, the protein phosphatase PP5. Sequence analysis of PfPP5 reveals significant differences in its Hsp90-interaction domain compared with human PP5. The aim of this project is to dissect the molecular details of these differences, through determining the atomic structure of the phosphatase by X-ray protein crystallography, biophysical analysis of the interaction between PfPP5 and PfHsp90 and in vivo studies using a mouse model of malaria. We hope to understand if these differences can be exploited to provide a new platform for drug discovery initiatives to inhibit infection by P. falciparum.

Requirements
Suitable candidates will have a 2:1 or above in biochemistry or another biological science. Candidates should also have previous research experience and an enthusiasm for laboratory research. The candidate will have the opportunity to train in structural and biochemical techniques, as well as the genetic manipulation and cellular biology of parasites.

Key References:

  1. Pallavi, R. et al., 2010 J. Biol. Chem., 285, 37964-75.
  2. Vaughan, C. K. et al., 2008, Mol. Cell, 31, 886-895.
  3. Yang, J. et al., EMBO J., 2005, 24, 1-10.
  4. Dobson, S. et al., BMC Microbiol., 2001, 1, 31-39.

Further details about the project may be obtained from:

Lead Supervisor: Cara Vaughan; c.vaughan@mail.cryst.bbk.ac.uk, http://people.cryst.bbk.ac.uk/~ubcg72a/Home.html

Co-Supervisor: Johannes Dessens; Johannes.Dessens@lshtm.ac.uk, http://www.lshtm.ac.uk/people/dessens.johannes

Further information about PhDs at Birkbeck College is available from:

http://www.bbk.ac.uk/biology/prospective-students/studentships

Application forms and details about how to apply are available from:

http://www.bbk.ac.uk/biology/prospective-students/studentships/bloomsbury/

Registry
Birkbeck, University of London
Malet Street
Bloomsbury
London WC1E 7HX
UK

Contact Tel: +44 (0) 20 7380 3020 

Departmental/School PhD Administrator:
Tim Hoe
Email: t.hoe@mail.cryst.bbk.ac.uk
Contact Tel: +44 (0) 20 7079 0745

With their application, candidates are required to include:

A single file (.doc, .rtf or .pdf) containing a one-page statement supporting your application for this project, and your current CV. Please also include your student reference number (from the online application form) in this file.

When applying, please indicate where you found out about this studentship (please state the publication title/ web address).

Closing date for applications: This studentship is now closed