Professor Jean Manson

The Roslin Institute

Research Interests

The transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases affecting humans and animals. TSEs present with characteristic pathology which can include neuronal loss, reactive astrogliosis, deposition of disease-associated prion protein (PrP) which may form amyloid plaques, and vacuolation giving a characteristic spongiform appearance to brain tissue. The aim of our group is to examine the role of host PrP in the outcome of natural TSEs like scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakobs disease (CJD) as well as a large range of experimental TSE models available in the Neurobiology Division. Basic research into neurodegenerative processes has also led into study of other diseases such as Alzheimer's disease.

The group uses a variety of models from the molecular to whole animal level of study. In particular we have produced a battery of unique transgenic mouse models via gene-targeting including:

  • PrP knockout
  • PrP species gene replacement
  • Conditional (Cre/LoxP) PrP models
  • PrP N-glycosylation site deficient models

The gene targeting approach ensures that the altered PrP allele remains in the correct genomic location under control of the endogenous promoter thus avoiding PrP over-expression that may lead to altered phenotypes. These models allow the group to investigate the effects of PrP sequence and glycosylation and also expression in various cell-types or at specific time-points during disease.

The group also employs a sheep model for investigation into transfer of TSE infection via blood transfusion, particularly relevant to the current identification of secondary transmission of new variant CJD in humans by the same route.

Our research programme currently receives funding from a number of different sources including BBSRC, MRC, DEFRA, DoH and EU.

Selected Publications

  • Abigail B. Diack, Enrico Cancellotti, Sukhvir Mahal, Robert Somerville, Deborah Brown, Pedro Piccardo, Charles Weissmann, Jean C. Manson. 2013. Post-translational changes to PrP alter transmissible spongiform encephalopathy strain properties. Prion Vol: 7 Pages: 85-85. More»
  • Matthew T. Bishop, Robert G. Will, Jean C. Manson. 2010. Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties. Proceedings of the National Academy of Sciences Vol: 107 Pages: 12005-12010. More»
  • Barry M. Bradford, Nadia L. Tuzi, M. Laura Feltri, Caroline McCorquodale, Enrico Cancellotti, Jean C. Manson. 2009. Dramatic Reduction of PrPC Level and Glycosylation in Peripheral Nerves following PrP Knock-Out from Schwann Cells Does Not Prevent Transmissible Spongiform Encephalopathy Neuroinvasion. Journal of Neuroscience Vol: 29 Pages: 15445-15454. More»
  • N. L. Tuzi, E. Cancellotti, Herbert Baybutt, L. Blackford, Barry Bradford, Christopher Plinston, A. Coghill, Patricia Hart, Pedro Piccardo, R. M. Barron, J. C. Manson. 2008. Host PrP glycosylation: a major factor determining the outcome of prion infection. PLoS Biology Vol: 6 Pages: 872-882. More»
  • E. Cancellotti, Barry Bradford, N. L. Tuzi, R. D. Hickey, Deborah Brown, K. L. Brown, R. M. Barron, Dorothy Kisielewski, Pedro Piccardo, J. C. Manson. 2010. Glycosylation of PrPC determines timing of neuroinvasion and targeting in the brain following transmissible spongiform encephalopathy infection by a peripheral route. Journal of Virology Vol: 84 Pages: 3464-75. More»