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- Introduction
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1. Prions and amyloids: introduction
- Prof. Reed Wickner
- Mammalian Prions
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2. Transgenic mouse models of prion diseases
- Prof. Glenn Telling
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3. Mechanism of prion generation in vitro
- Dr. Surachai Supattapone
- Non-Prion Amyloids
- Yeast Prions
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6. Chaperones and prions
- Prof. Yury Chernoff
- Beneficial Amyloids
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7. The dark side of amyloid: PMEL, a natural amyloid in melanosome biogenesis
- Prof. Michael Marks
- Archived Lectures *These may not cover the latest advances in the field
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8. Predicting TSE transmission
- Prof. Jean Manson
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10. Yeast and fungal prions: a help or a hindrance?
- Prof. Reed Wickner
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11. [PIN+]: prions beget prions
- Prof. Susan Liebman
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12. Yeast prions and protein chaperones
- Dr. Daniel Masison
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13. Mechanisms of yeast prion propagation
- Prof. Mick Tuite
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14. Propagation and variability of the yeast [PSI+] prion
- Prof. Michael Ter-Avanesyan
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15. The genetics and biology of the [Het-s] prion of Podospora
- Prof. Sven Saupe
Printable Handouts
Navigable Slide Index
- Introduction
- Hundreds of thousands of cattle infected with BSE
- The vCJD epidemic
- New challenges
- Identify source of infection
- Defining the TSE strain: in vivo
- Defining the TSE strain: in vitro
- Understand host susceptibility
- The prion hypothesis
- Strategy
- Targeting the PrP gene - step 1 in vitro
- Targeting the PrP gene - step 2 in vivo
- Targeting the murine PrP gene
- PrP is required for TSE disease
- PrnP gene dosage influences the incubation time
- Human mutations and polymorphisms
- Modelling susceptibility between species
- Other factors controlling incubation time
- Modelling human susceptibility to TSEs
- vCJD transmission to transgenic mice
- Transgenic mice infected with vCJD
- Predicting the risk of transmission of vCJD
- An amino acid alteration and host susceptibility (1)
- An amino acid alteration and host susceptibility (2)
- The 101L mutation decreases incubation time
- Scrapie is an infectious disease, not a genetic one
- PrP glycosylation and host susceptibility
- PrP glycosylation deficient mice
- Results in the absence of PrP glycosylation
- Effect on incubation time in the absence of G2
- G1 Absence provides resistance to ME7
- Host PrP glycosylation deficient mice
- Define routes of transmission to animals
- Possible routes of transmission of vCJD
- Modelling vCJD by blood transfusion in sheep
- Advantages of using sheep
- Initial experiments
- Results
- Transmission of vCJD by blood transfusion
- Questions
- Define transmission within animal
- Transmission of TSE agent within a host
- FDC depletion blocks oral scrapie transmission
- The role of PrP expression
- Inducible expression of PrP
- Predicting host range of a TSE strain
- Carriers of infection
- vCJD risk of transmission in gene targetted mice
- Prevalence of PrP in UK tissue samples
- Diagnosis and co-located PrPSc and infectivity
- Infectious brains with no abnormal forms of PrP
- Abnormal PrP can accumulate without disease
- Mouse inoculated with a human TSE disease
- What is the role of PrP amyloid?
- What is the role of PrPSc in disease?
- Protein misfolding and infectivity
- Key areas still to be addressed
- Acknowledgements
Topics Covered
- The TSEs continue to pose a problem to animal and human health
- The vCJD epidemic appears to be in decline but new risks of human to human transmission are now apparent
- Chronic wasting disease is a major problem currently in the US although its presence has not yet been detected in Europe
- Predicting and preventing transmission of disease requires an understanding of the routes of transmission within and between animals and the host factors which determine susceptibility
- We have studied natural disease and both in vivo and in vitro model systems to unravel the basic mechanisms of disease
- PrP protein has a central role in the outcome disease and mutations and polymorphisms in host PrP can profoundly alter the host's susceptibility to a TSE agent
- Precisely how host PrP influences the outcome of disease has not been established
- Both mutations and glycosylation can profoundly influence transmission both within and between species
Links
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Talk Citation
Manson, J. (2008, October 22). Predicting TSE transmission [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 5, 2024, from https://doi.org/10.69645/CGVX2807.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Jean Manson has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.