Development of the new yeast-based assays for prion properties

dc.contributor.advisor Chernoff, Yury O.
dc.contributor.author Sun, Meng en_US
dc.contributor.committeeMember Cairney, John
dc.contributor.committeeMember Lobachev, Kirill
dc.contributor.committeeMember Storici, Francesca
dc.contributor.committeeMember Wartell, Roger
dc.contributor.department Biology en_US
dc.date.accessioned 2013-01-17T21:46:35Z
dc.date.available 2013-01-17T21:46:35Z
dc.date.issued 2011-08-29 en_US
dc.description.abstract Prion is an infectious isoform of a normal cellular protein which is capable of converting the non-prion form of the same protein into the alternative prion form. Mammalian prion protein PrP is responsible for prion formation in mammals, causing a series of fatal and incurable prion diseases. (1) We constructed, for the first time, a two-component system to phenotypically monitor the conformational status of PrP in the yeast cells. In this system, the prion domain of Sup35 (Sup35N) was fused to PrP90-230, and the initial formation of the PrPSc-like conformation stimulated prion formation of Sup35N, which in turn converted soluble Sup35 into the prion isoform, leading to a detectable phenotype. Prion-like properties of PrP were studied in this novel yeast model system. Additionally, we employed this system to study amyloidogenic protein Aβ42 aggregation in the yeast model. It has been suggested that the ability to form transmissible amyloids (prions) is widespread among yeast proteins and is likely intrinsic to proteins from other organisms. However, the distribution of yeast prions in natural conditions is not yet clear, which prevents us from understanding the relationship between prions and their adaptive roles in various environmental conditions. (2) We modified and developed sequence and phenotype-independent approaches for prion detection and monitoring. We employed these approaches for prion-profiling among yeast strains of various origins. (3) Lastly, we found a prion-like state [MCS+] causing nonsense suppression in the absence of the Sup35 prion domain. Our results suggested that [MCS+] is determined by both a prion factor and a nuclear factor. The prion-related properties of [MCS+] were studied by genetic and biochemical approaches. en_US
dc.description.degree PhD en_US
dc.identifier.uri http://hdl.handle.net/1853/45831
dc.publisher Georgia Institute of Technology en_US
dc.subject Amyloid beta en_US
dc.subject [PSI+] en_US
dc.subject Prion detection en_US
dc.subject Prion induction en_US
dc.subject Mammalian prion protein en_US
dc.subject.lcsh Prions
dc.subject.lcsh Proteins
dc.subject.lcsh Prion diseases
dc.title Development of the new yeast-based assays for prion properties en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Chernoff, Yury O.
local.contributor.corporatename College of Sciences
local.contributor.corporatename School of Biological Sciences
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relation.isOrgUnitOfPublication c8b3bd08-9989-40d3-afe3-e0ad8d5c72b5
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