Senior Physical/Biological Chemist

Paul Barlow pnb01 at
Wed Sep 13 07:44:58 EST 1995

Job description

Institution :    BBSRC  Institute for Animal Health, Compton Laboratory,
                                (Near Newbury), Berkshire RG20 7NN

Principal Investigator :    Dr J. Hope   (E-Mail : james.hope at

Title of project :  Physical structure, folding and stability of  PrP protein

Start date :   01 December 1995          End date :  30 November 1998

Grade of post :      Band 6

The conversion of the normal form of the prion protein (PrPC) to its
protease-resistant isoform
(PrPSc) is a key process in the development of scrapie and related prion
diseases. PrPSc is enriched in preparations of infectious particles and, either
by itself or in association with other molecules, is regarded by many as the
infectious agent.  Spectral changes monitored (by circular dichroism or
fluorescence) during the thermal or chemical  denaturation of PrP27-30 (an
active fragment of PrPSc) indicate a  complex "melt" of this fibrillar form of
the protein,  possibly involving a transition state with similar properties to
a "molten globule".  Circular dichroism (CD), Fourier-transform infra-red
spectroscopy (FT-IR) and fluoresecence measurements on PrPC  and PrPSc give
estimates of a high alpha-helix secondary structure in PrPC,  less in PrPSc,
and least in PrP27-30 . This spectrocopic data and computer simulations of the
secondary and tertiary structure of PrP have led to a four-helix bundle model
of PrPC and a mechanism involving the switch of one or more of these helices to
beta-sheet structure when this normal isoform changes to its protease-resistant
forms (PrPSc and PrP27-30). Knowledge of PrP structure and an understanding of
the mechanism of PrPSc formation and prion replication are needed for rationale
drug design, therapy, prevention of intra-and inter-species  transmission and
the development of more effective methods of disinfection of the agents of BSE,
scrapie and Creutzfeldt-Jakob disease.  To compliment  studies on the natural
forms of PrPC and PrPSc and our transgenic programme of research on the
biological aspects of PrP in the spongiform encephalopathies, we are
investigating the structure, stability and folding of the wild-type and mutant,
 recPrP proteins.

To support this programe of work, we are seeking to appoint a senior
Biological/Physical Chemist  (Grade 6)  at IAH Compton to direct the
characterisation of recPrP by a variety of biophysical techniques including
mass spectrometry, Fourier Transform-infra red spectroscopy, circular
dichroism, fluorescence, surface plasmon resonance, laser light scattering,
ultra-centrifugation and
ultrafiltration. The preferred candidate will have extensive experience in at
least two of these areas of protein analysis. He/she will also take
responsibility for the setting up  the different permutations of solutions,
protein concentrations, etc need to crystallise the PrP protein and the
preliminary screening by light and electron microscopy of these liquors for

If you require more details about this post, please call 0131-667-5204), fax
(0131-668-3892) or mail
(above) Jim Hope, or contact the Personnel Officer, Institute for Animal
Health, Compton,
Berkshire RG20 7NN (phone, 01635-578411; fax, 01635-577131; e-mail ;
hughesj at
The Institute for Animal Health is an Equal Opportunities Employer. 

More information about the Proteins mailing list