Title of project: Development of low cost, therapeutic antibody treatment for flavivirus
encephalitis
Director of Studies: Dr S Galbraith
Second Supervisor: Dr V Postis
Overview of project
For the last twenty years, RNA viruses are the biggest emerging pathogen threat. It is environmental
change coupled with tropical urbanisation and globalization that makes flaviviruses a worldwide
danger to public health. Japanese encephalitis is the most important emerging encephalitis
furthermore, the WHO report that half of the world is at risk from Dengue infection. Currently no
treatments exist for any flavivirus disease. Extraction of protective antibodies from Asian blood donors
makes intravenous immunoglobulin (antibody) treatments expensive and difficult to produce.
The flavivirus envelope (E) protein is responsible for virus attachment to the cell and triggering cellular
infection. Human vaccination against flavivirus encephalitis has shown that flaviviruses share
common protective epitopes in their E proteins (Mansfield et al., 2011). The screening of artificial
antibody and antibody mimetic libraries will allow isolation of molecules that will prevent flavivirus
infection. Additionally solving the atomic structure of the E protein will help to understand virus particle
assembly and therefore permit informed drug design.
Link to Faculty Research Themes
School of Rehabilitation and Health Sciences and University of Leeds.
3A (Allied Health Professions, Dentistry, Nursing and Pharmacy) and 5A (Biological Sciences).
Outline of project including proposed timescales
This project will use a model flavivirus that is not associated with human disease: the langat virus
(LGT). The E protein will be crystalised after generation of recombinant protein. Academic and
commercial libraries will be screening for molecules that blocks binding of the viral particles to cells.
Potential antibodies will be tested for their ability to neutralize virus using the plaque reduction
neutralization test.
Identification of a protective neutralizing antibody will allow inexpensive, high throughput production of
intravenous immunoglobulin therapy for flavivirus infection, which will be published in Journal of
Virology (impact factor 4.6) and Journal of Biological Chemistry (impact factor 4.6). Work from this
proposal will be submitted as a program grant to the Medical Research Council Infection and
Immunity board for development of a new therapeutic antibody treatment for flavivirus encephalitis.
The student involved in this work will gain experience in key virology, biochemistry and immunology
techniques providing them with valuable skills for employment in academia and the pharmaceutical
industry.
Further information
To apply you must be eligible for NHS Continuing Professional Development (CPD) funding and have
the support of your line manager in writing. General enquiries should be directed by email to the
Faculty Research Director r.hogston@leedsbeckett.ac.uk to discuss the project further please contact
the Director of Studies S.E.Galbraith@leedsbeckett.ac.uk
Applications should be made on line here
http://www.leedsbeckett.ac.uk/research/research-degrees/research-studentships-andfees-only-bursaries/