Nature of TSE infection and Routes of Transmission
Lead Research Organisation:
University of Edinburgh
Department Name: The Roslin Institute
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
We aim to study the biochemical and biophysical nature of different strains of agent and their modes of transfer from animal to animal for the development of specific disease control in combination with efficient health and environmental protection measures. The refinement of diagnostic methods and genetic programmes will be used to eradicate novel TSE agents and provide models for risk reduction in other diseases. We will follow the agent in its route into the host and study the cellular, molecular and genetic mechanisms that enhance or prevent efficient transmission. The objectives of this theme are: To define TSE strains. Understand the TSE infectious agent and diagnosing disease. Define routes of transmission between animals. Understand genetic control of susceptibility/resistance. To define the role of PrP gene regulation in TSE disease. Investigate therapeutic intervention.
Planned Impact
unavailable
Organisations
- University of Edinburgh (Lead Research Organisation)
- U.S. Department of Agriculture USDA (Collaboration)
- French Agency for Food Safety (AFSSA) (Collaboration)
- National Institute of Allergy and Infectious Diseases (NIAID) (Collaboration)
- Colorado State University (Collaboration)
- Experimental Zooprophylactic Institute of Piedmont (Collaboration)
- Veterinary Laboratories Agency (Collaboration)
People |
ORCID iD |
| Jean Manson (Principal Investigator) |
Publications
Barr J
(2010)
Differential protein expression profiling in BSE disease
in Archives of Physiology and Biochemistry
Barr JB
(2009)
Differential protein profiling as a potential multi-marker approach for TSE diagnosis.
in BMC infectious diseases
Bibby DF
(2008)
Application of a novel in vitro selection technique to isolate and characterise high affinity DNA aptamers binding mammalian prion proteins.
in Journal of virological methods
Burgess ST
(2009)
Identification of adjacent binding sites for the YY1 and E4BP4 transcription factors in the ovine PrP (Prion) gene promoter.
in The Journal of biological chemistry
Campbell L
(2013)
The PrPC C1 fragment derived from the ovine A136R154R171 PRNP allele is highly abundant in sheep brain and inhibits fibrillisation of full-length PrPC protein in vitro
in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Cancellotti E
(2010)
Glycosylation of PrPC determines timing of neuroinvasion and targeting in the brain following transmissible spongiform encephalopathy infection by a peripheral route.
in Journal of virology
Chong A
(2015)
Archival search for historical atypical scrapie in sheep reveals evidence for mixed infections.
in The Journal of general virology
Chong A
(2015)
Archival search for historical atypical scrapie in sheep reveals evidence for mixed infections.
in The Journal of general virology
Foster J
(2008)
Atypical scrapie in a sheep in a closed UK flock with endemic classical natural scrapie.
in The Veterinary record
| Description | We have identified novel DNA-derived aptamers that bind mammalian prion proteins and that could form part of future diagnostic tests for TSE disease. We have also developed a novel method to allow high-resolution strain differentiation using mass spectrometric analysis of N-terminal peptides. Previous studies by us and others had shown a significant species barrier to infection of humans with cattle BSE. However following transmission of BSE through sheep, increased susceptibility to infection was observed in transgenic mice homozygous for human 129M PrP. This is despite the observation that both cattle and sheep BSE can equally convert human 129M PrP in vitro. These data suggest that other genetic factors in addition to PrP sequence can influence zoonotic transmission. We have developed new methods of identifying TSE strains in sheep, particularly useful when studying mixed infections. Genetic control of susceptibility/resistance may also function through control of PRNP gene expression. We have identified new control sites at the PRNP gene locus which may be important in disease control. Understanding how natural scrapie spreads between individuals and between flocks is important in the development of control measures. In comparison of classical and atypical scrapie we have accumulated information on two populations now being used in detailed genomic sequencing projects to provide further information on genetic control of atypical scrapie. We have revealed a new association of ovine PRNP codon 141 with BSE susceptibility and confirmed association of PRNP with goat scrapie in the UK. Our studies of European and American deer have highlighted the variability of the PRNP gene and its association with susceptibility in cervids which are at risk of developing chronic wasting disease (CWD). We have also shown that most carnivorous scavengers exposed to CWD appear to be susceptible based on their PRNP genotypes. Our studies have revealed novel regulation mechanisms of the ovine PRNP gene, which may be associated with scrapie susceptibility. |
| Exploitation Route | These findings have advanced the basic knowledge of prion research and been published in peer review journals. |
| Sectors | Agriculture Food and Drink |
| Description | EU policy on safety of embryos with regard to scrapie in sheep |
| Geographic Reach | Europe |
| Policy Influence Type | Membership of a guideline committee |
| Impact | Affects use of sheep embryo transfer in international trade. To prevent scrapie transmission, the advice is to use genetically resistant animals. |
| Description | Member of the CJD Sample Oversight Committee Group |
| Geographic Reach | National |
| Policy Influence Type | Membership of a guideline committee |
| Impact | The committee aims to facilitate the development of diagnostics for vCJD through working with developers and providing access to rare samples |
| Description | A study of scrapie affected goat herds |
| Amount | £165,073 (GBP) |
| Funding ID | SE1956 |
| Organisation | Department For Environment, Food And Rural Affairs (DEFRA) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2008 |
| End | 05/2011 |
| Description | Defra R&D |
| Amount | £1,206,000 (GBP) |
| Funding ID | SE1436 |
| Organisation | Department For Environment, Food And Rural Affairs (DEFRA) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2003 |
| End | 12/2012 |
| Description | Defra R&D |
| Amount | £2,348,412 (GBP) |
| Funding ID | SE1852/1853 |
| Organisation | Department For Environment, Food And Rural Affairs (DEFRA) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2003 |
| End | 12/2014 |
| Description | Defra R&D contract |
| Amount | £430,414 (GBP) |
| Funding ID | SE1447 |
| Organisation | Department For Environment, Food And Rural Affairs (DEFRA) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2013 |
| End | 09/2016 |
| Description | Proposal for improvement of goat BSE discriminative diagnosis. |
| Amount | £143,949 (GBP) |
| Funding ID | EU79-0558(93-3740) |
| Organisation | European Commission |
| Sector | Public |
| Country | Belgium |
| Start | 04/2008 |
| End | 11/2012 |
| Description | Proposal for improvement of goat BSE discriminative diagnosis.(II) |
| Amount | £435,414 (GBP) |
| Organisation | Department For Environment, Food And Rural Affairs (DEFRA) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2008 |
| End | 11/2012 |
| Description | Genetic association with scrapie and BSE in sheep and goats |
| Organisation | Veterinary Laboratories Agency |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Genetic analysis of sheep and goat samples. Study design and interpretation of data. Manuscript preparation |
| Collaborator Contribution | Sample provision, pathology expertise and manuscript preparation. |
| Impact | González, L., Martin, S., Hawkins, S.A.C. , Goldmann, W., Jeffrey, M., Sisó, S. (2010) Pathogenesis of natural goat scrapie: modulation by host PRNP genotype and effect of co-existent conditions. Vet Res. 41:48 Konold, T., Bone, G.E., Phelan, L.J., Simmons, M.M., González, L., Sisó, S., Goldmann, W., Cawthraw, S., Hawkins, S. A.C. (2010) Monitoring of clinical signs in goats with transmissible spongiform encephalopathies. BMC Vet Res 6:13 González, L., Martin, S., Sisó, S., Konold, T., Ortiz-Peláez, A., Phelan, L., Goldmann, W., Stewart, P., Saunders, G., Windl, O., Jeffrey, M., Hawkins, S.A.C., Dawson, M. and Hope, J. (2009) High prevalence of scrapie in a dairy goat herd:tissue distribution of disease-associated PrP and effect of PRNP genotype and age. Vet Res. 40:65 |
| Start Year | 2008 |
| Description | QuIC analysis of low PrPSc mouse models |
| Organisation | National Institute of Allergy and Infectious Diseases (NIAID) |
| Department | Rocky Mountain Laboratories |
| Country | United States |
| Sector | Public |
| PI Contribution | Provision of brain tissue from an unique mouse model of TSE disease |
| Collaborator Contribution | Performed QuIC analysis of material from our mouse model |
| Impact | Vascellari S, Orrù CD, Hughson AG, King D, Barron RM, Wilham JM, Baron GS, Race B, Pani A and Caughey B (2012). Prion seeding activities of mouse scrapie strains with divergent PrPSc protease sensitivities and amyloid plaque content using RT-QuIC and eQuIC. PLoS One 7:e48969 |
| Description | Seeding protein aggregation in mice |
| Organisation | Colorado State University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Analysis of amyloid plaque seeding in mouse brain |
| Collaborator Contribution | Provision of mice and tissue from animals overexpressing 101L PrP |
| Impact | Piccardo P, King D, Telling G, Manson JC and Barron RM (2013). Dissociation of prion protein amyloid seeding from transmission of a spongiform encephalopathy. J Virol. 87:12349-12356 doi: 10.1128/JVI.00673-13 |
| Description | Zoonotic transmission of prions |
| Organisation | Experimental Zooprophylactic Institute of Piedmont |
| Country | Italy |
| Sector | Charity/Non Profit |
| PI Contribution | Performed prion transmission studies into human PrP and bovine PrP transgenic mice using bovine brain infected with BASE |
| Collaborator Contribution | Provided the BASE brain tissue |
| Impact | Wilson R, Hart P, Piccardo P, Hunter N, Casalone C, Baron T, and Barron RM (2012). Bovine PrP expression levels in transgenic mice influence transmission characteristics of atypical BSE. Journal of General Virology 93:1132-1140 Wilson R, Plinston C, Hunter N, Casalone C, Corona C, Tagliavini F, Suardi S, Ruggerone M, Moda F, Graziano S, Sbriccoli M, Cardone F, Pocchiari M, Ingrosso L, Baron T, Richt J, Andreoletti O, Simmons M, Lockey R, Manson JC, and Barron RM (2012). Chronic wasting disease and atypical forms of BSE and scrapie are not transmissible to mice expressing wild-type levels of human PrP. Journal of General Virology 93:1624-1629 |
| Start Year | 2007 |
| Description | Zoonotic trasnmission of prions |
| Organisation | French Agency for Food Safety (AFSSA) |
| Country | France |
| Sector | Public |
| PI Contribution | Performed transmission experiments to human PrP and bovine PrP transgenic mice using H-BSE infected brain tissue |
| Collaborator Contribution | Provided the H-BSE infected brain tissue |
| Impact | Wilson R, Hart P, Piccardo P, Hunter N, Casalone C, Baron T, and Barron RM (2012). Bovine PrP expression levels in transgenic mice influence transmission characteristics of atypical BSE. Journal of General Virology 93:1132-1140 Wilson R, Plinston C, Hunter N, Casalone C, Corona C, Tagliavini F, Suardi S, Ruggerone M, Moda F, Graziano S, Sbriccoli M, Cardone F, Pocchiari M, Ingrosso L, Baron T, Richt J, Andreoletti O, Simmons M, Lockey R, Manson JC, and Barron RM (2012). Chronic wasting disease and atypical forms of BSE and scrapie are not transmissible to mice expressing wild-type levels of human PrP. Journal of General Virology 93:1624-1629 |
| Start Year | 2007 |
| Description | Zoonotic trasnmission of prions |
| Organisation | U.S. Department of Agriculture USDA |
| Department | National Animal Disease Center |
| Country | United States |
| Sector | Public |
| PI Contribution | Performed transmission studies in human PrP and bovine PrP transgenic mice using Chronic Wasting Disease infected brain tissue |
| Collaborator Contribution | Provided the Chronic Wasting Disease infected brain tissue |
| Impact | Wilson R, Plinston C, Hunter N, Casalone C, Corona C, Tagliavini F, Suardi S, Ruggerone M, Moda F, Graziano S, Sbriccoli M, Cardone F, Pocchiari M, Ingrosso L, Baron T, Richt J, Andreoletti O, Simmons M, Lockey R, Manson JC, and Barron RM (2012). Chronic wasting disease and atypical forms of BSE and scrapie are not transmissible to mice expressing wild-type levels of human PrP. Journal of General Virology 93:1624-1629 |
| Start Year | 2007 |
| Description | BNA Streetfair |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | British Neuroscience Association Streetfair, held at the Barbican Centre in London alongside the annual BNA symposium. Activity to communicate work we do on TSE disease, protein misfolding and neurodegeneration to the public |
| Year(s) Of Engagement Activity | 2013 |
| Description | Big Bang, Schools science competition |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | I was a judge moderator for Big Bang, a schools competition for science projects. |
| Year(s) Of Engagement Activity | 2012,2013 |
| Description | EFSA Goat TSE committee |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Expert committee member to advise on the use of selective breeding for TSE resistance in Cyprus |
| Year(s) Of Engagement Activity | 2009 |
| Description | Highland Show, Ingliston. Scotland's biggest agricultural show |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Presenting posters of research and games to interest youngsters. Answering resulting questions. |
| Year(s) Of Engagement Activity | 2013 |
| Description | Informa Biopharmaceutical Raw Materials Conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Talk about risks of TSE infection in biological produces and processes |
| Year(s) Of Engagement Activity | 2012 |
| Description | Presentation to SEAC on risks of sheep BSE to humans |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Presentation to the Spongiform Encephalopathy Advisory Committee regarding recent research results on transmission of ovine BSE. |
| Year(s) Of Engagement Activity | 2009 |
| Description | Press Interview on Americal BASE case for Science News (online article) |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Press interview with Science News on recent identification of a case of atypical BSE in the USA |
| Year(s) Of Engagement Activity | 2012 |
| Description | Prion 2016 chair and invited speaker |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | invited talk to international meeting |
| Year(s) Of Engagement Activity | 2016 |
| Description | Roslin Institute Open Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Each year we run an activity designed to engage the public and introduce them to the work we do on TSE diseases, protein misfolding and neurodegeneration |
| Year(s) Of Engagement Activity | 2012,2013,2014,2015,2016 |
| Description | Roslin Institute public open day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Science games for children. Questions from well informed children and more questions from their parents. |
| Year(s) Of Engagement Activity | 2014,2015 |
| Description | University of Glasgow Dental School Evening Symposium; vCJD- frequently asked questions for dental practitioners. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | Public Lecture to Dental Practitioners on the risks of prion disease |
| Year(s) Of Engagement Activity | 2010 |
| Description | oral presentation at Prion Conference 2011 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Discussion of my research with international colleagues. New collaborations |
| Year(s) Of Engagement Activity | 2011 |