Abstract: Screening methods for identifying substances that provide therapeutic value for various diseases associated with protein misfolding are provided. Genetic and chemical screening methods are provided using a yeast system. The methods of the invention provide a rapid and cost-effective method to screen for compounds that prevent protein misfolding and/or protein fibril formation and/or protein aggregation which includes numerous neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease as well as non-neuronal diseases such as type 2 diabetes.

Abstract: Using the Sup35 prion proteins of two distantly related yeast species, it is established that prion replication is initiated by small elements of primary sequence, which can be identified using arrays of short peptides. Subtle differences in replication elements govern the formation of distinct aggregate conformations (prion strains) and also determine their species-specific seeding activities. A Sup35 chimera that promiscuously forms prions in more than one species does so by virtue of carrying the replication element of each species. Mutations or conditions that cause the chimera to assemble into distinct prion strains favor recognition of distinct replication elements. Therefore, subtle differences in small sequences that constitute prion replication elements encode important determinants of prion propagation and transmission.

Abstract: The present invention provides a yeast cell based system for determining factors that control the folding of amyloid proteins of diverse origins. Further the present invention provides methods of using such a system to screen for reagents that affect amyloid formation, a process that is integral to several devastating human disease including Creutzfeld-Jacob disease (CJD), fatal familial insomnia (FFI), Gertsmann-Straussler-Scheinker (GSS) syndrome, and kuru. The system of the present invention provides a rapid screening system to quickly and cheaply identify reagents that affect the folding and aggregation properties of the target protein.

Abstract: The present invention provides novel polypeptides comprising a prion-aggregation domain and a second domain; novel polynucleotides encoding such polypeptides; host cells transformed or transfected with such polynucleotides; novel fibrils with specific functionalities and unusually high chemical and thermal stability; and methods of making and using the foregoing in, for example, the production of nanoscale devices.

Abstract: The present invention provides novel polypeptides comprising a prion-aggregation domain and a second domain; novel polynucleotides encoding such polypeptides; host cells transformed or transfected with such polynucleotides; novel fibrils with specific functionalities and unusually high chemical and thermal stability; and methods of making and using the foregoing.

Abstract: The present invention provides novel polypeptides comprising a prion-aggregation domain and a second domain; novel polynucleotides encoding such polypeptides; host cells transformed or transfected with such polynucleotides; and methods of making and using the foregoing.

Abstract: Disclosed are methods for identifying compounds that modulate huntingtinmediated impairment of protein degradation pathways. Compounds identified by such screens can be used as candidate drugs for the treatment of prevention of polyglutamine diseases such as Huntington's Disease.

Abstract: Screening methods for identifying substances that provide therapeutic value for various diseases associated with protein misfolding are provided. Genetic and chemical screening methods are provided using a yeast system. The methods of the invention provide a rapid and cost-effective method to screen for compounds that prevent protein misfolding and/or protein fibril formation and/or protein aggregation which includes numerous neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease as well as non-neuronal diseases such as type 2 diabetes.

Abstract: The invention relates to compounds which inhibit aggregation of proteins or peptides, or disaggregate protein aggregates, and thereby antagonize the toxic effects of such aggregates. The invention also relates to methods for using such compounds and methods for discovering compounds that inhibit protein or peptide aggregation.

Abstract: Screening methods for identifying substances that provide therapeutic value for various diseases associated with protein misfolding are provided. Genetic and chemical screening methods are provided using a yeast system. The methods of the invention provide a rapid and cost-effective method to screen for compounds that prevent protein misfolding and/or protein fibril formation and/or protein aggregation which includes numerous neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease as well as non-neuronal diseases such as type 2 diabetes.

Abstract: The present invention provides novel polypeptides comprising a prion-aggregation domain and a second domain; novel polynucleotides encoding such polypeptides; host cells transformed or transfected with such polynucleotides; novel fibrils with specific functionalities and unusually high chemical and thermal stability; and methods of making and using the foregoing.

Abstract: Screening methods for identifying substances that provide therapeutic value for various diseases associated with protein misfolding are provided. Genetic and chemical screening methods are provided using a yeast system. The methods of the invention provide a rapid and cost-effective method to screen for compounds that prevent protein misfolding and/or protein fibril formation and/or protein aggregation which includes numerous neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease as well as non-neuronal diseases such as type 2 diabetes.

Abstract: The present invention provides novel polypeptides comprising a prion-aggregation domain and a second domain; novel polynucleotides encoding such polypeptides; host cells transformed or transfected with such polynucleotides; novel fibrils with specific functionalities and unusually high chemical and thermal stability; and methods of making and using the foregoing.

Abstract: Methods of screening candidate agents to identify lead compounds for the development of therapeutic agents for the treatment of a neurodegenerative disease, such as Huntington's Disease and Parkinson's Disease and methods for identifying a mutation in, or changes in expression of, a gene associated with neurodegenerative disease, such as Huntington's Disease and Parkinson's Disease, are provided.

Abstract: The present invention provides novel polypeptides comprising a prion-aggregation domain and a second domain; novel polynucleotides encoding such polypeptides; host cells transformed or transfected with such polynucleotides; and methods of making and using the foregoing.

Abstract: Disclosed are yeast ectopically expressing abnormally processed proteins and methods of screening to identify compounds that modulate the function of such abnormally processed proteins in yeast. Compounds identified by such screens can be used to treat or prevent diseases associated with abnormally processed proteins or protein misfolding. Such diseases include Parkinson's Disease, Parkinson's Disease with accompanying dementia, Lewy body dementia, Alzheimer's disease with Parkinsonism, and multiple system atrophy.

Abstract: Screening methods for identifying substances that provide therapeutic value for various diseases associated with protein misfolding are provided. Genetic and chemical screening methods are provided using a yeast system. The methods of the invention provide a rapid and cost-effective method to screen for compounds that prevent protein misfolding and/or protein fibril formation and/or protein aggregation which includes numerous neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease as well as non-neuronal diseases such as type 2 diabetes.

Abstract: The present invention regards a method of unmasking or revealing genetic variation in eukaryotic organisms, such as plants, to eukaryotic organisms, particularly plants, produced by the method, and eukaryotic organisms, particularly plants, that exhibit a phenotype (phenotype trait) masked by Hsp90 function (activity). Specifically, the present invention is directed to the detecting genetic variation in a plant by interfering with the Hsp90 buffer system. More specifically, endogenous Hsp90 activity is inhibited by drugs or genetic manipulation that results in the manifestation of pre-existing yet otherwise undetected genetic variations, such as polymorphisms.

Abstract: A transgenic plant having increased stress tolerance, such as thermotolerance, comprises a Hsp100 family nucleic acid sequence. The invention is also directed to methods of producing products from transgenic Hsp100 plants.

Abstract: This invention relates to the identification, isolation, purification and manipulation of genetic stress response systems, and more particularly, to genes and expression products of those genes that are components of those systems. These components may be used to protect against potentially toxic stress factors. Stress factors include heat, alcohol and heavy metal ions. A family of stress protector proteins with apparent molecular weights about 100 kd, the hsp100 proteins, are an aspect of this invention. Other stress protector proteins are also within the scope of this invention to enhance or inhibit biological stress response. Applications of this invention to recombinant DNA technology, to commercial methods of food preparation and processing, and to methods of enhancing the stress response of plants and animals, are presented.