Liming Li
Northwestern University At Chicago
Project start date: 2008-02-01
Project end date: 2013-01-31
Sponsored Links Excellgen http://Excellgen.com
ELUCIDATING THE RELATIONS OF HEAT SHOCK FACTORS, MOLECULAR CHAPERONES AND PRIONS
Liming Li, Assistant Professor
Northwestern University, 750 N. Lake Shore Drive, 7th, Chicago, Il 60611
Grant 5R01NS056086-03 from National Institute Of Neurological Disorders And Stroke
Keywords: Anabolism; Analysis, Data; Animal Model; Animal Models and Related Studies; Animal Welfare; Anxiety; Bibliography; Bovine Spongiform Encephalopathy; CJD; CJDs (Creutzfeldt-Jakob Disease); Cells; Chaperone; Chronic Wasting Disease; Complex; Country; Creutzfeldt-Jacob Disease; Creutzfeldt-Jakob Disease; Creutzfeldt-Jakob Syndrome; Data Analyses; Ecological impact; Encephalitis, Bovine Spongiform; Encephalopathy, Bovine Spongiform; Endomycetales; Environment; Environmental Impact; Epidemic; Equipment; Ethics Committees, Research; Evaluation; Goals; HSP; Heat Shock; Heat shock proteins; Heat-Shock Reaction; Heat-Shock Response; IACUC; IRBs; Impact, Environmental; Institutional Animal Care and Use Committee; Institutional Review Boards; International; Jakob-Creutzfeldt Disease; Limes; Link; Mad Cow Disease; Maintenance; Maintenances; Methods; Molecular Chaperones; Molecular Configuration; Molecular Conformation; Molecular Stereochemistry; Outcome; PSI; Play; PrP Proteins; Principal Investigator; Prion Proteins; Prions; Production; Programs (PT); Programs [Publication Type]; Protein Structure Initiative; Proteins; Research; Research Ethics Committees; Research Resources; Resources; Role; S cerevisiae; Saccharomyces cerevisiae; Saccharomycetales; Spongiform Encephalopathy, Subacute; Stress; Stress Proteins; Suggestion; Testing; Variant; Variation; Vertebrate Animals; Vertebrates; Wasting Disease, Chronic; Yeast, Baker`s; Yeast, Brewer`s; Yeast, Budding; ing; base; biosynthesis; cell type; conformation; conformational state; experiment; experimental research; experimental study; expiration; gene product; human subject; interest; model organism; novel; programs; protein folding; research study; response; social role; vertebrata; yeast prion
Project start date: 2008-02-01
Project end date: 2013-01-31
Budget start date: 1-FEB-2010
Budget end date: 31-JAN-2011
PFA/PA: PA-07-070
5R01NS056086-03 (2010): $324492
Grants awarded to Liming Li
ELUCIDATING THE RELATIONS OF HEAT SHOCK FACTORS, MOLECULAR CHAPERONES AND PRIONS
Liming Li, Assistant Professor
Northwestern University, 750 N. Lake Shore Drive, 7th, Chicago, Il 60611
Grant 3R01NS056086-02S1 from National Institute Of Neurological Disorders And Stroke
Abstract: Despite decades of scientific research and heightening public and governmental anxiety over the potential dangers of infectious proteins and their role in epidemics such as new variant Creutzfeldt-Jacob disease, Mad Cow disease, and chronic Wasting disease, the mechanisms responsible for the conversion of a normal cellular protein into an infectious prion protein continue to defy understanding. The cellular factors instrumental to the protein conformational changes that result in prion formation, as well as those factors necessary for the subsequent stabilization of the altered prion conformation, remain a mystery. Considering that prion formation and inheritance are tightly related to the protein folding machinery, we propose to investigate the link between prion formation and heat shock transcriptional factors (HSFs). HSFs are evolutionally conserved transcriptional factors responsible for the biosynthesis of the majority of molecular chaperones, which are essential for protecting cells from extreme harsh conditions by refolding or dis-aggregating denatured proteins produced during the stress. Several molecular chaperones are also shown to play essential roles in prion propagation. Using the budding yeast Saccharomyces cerevisiae as the model organism, we propose to elucidate the relationship between HSFs and prion formation/propagation. Our long-term goal of the proposed research is to identify protein factors whose functions are regulated by HSFs and are essential for prion formation/propagation. The specific aims are 1) to examine the regulatory role of heat shock protein 90kDa (Hsp90) complex in de novo formation and "strain" maintenance of [PSI+]; 2) to test if HSF and Hsp90 complex regulate other yeast prions. We will investigate if the effects of HSF and Hsp90/cochaperones are [PSI+] specific 3) to identify additional novel factors that are HSF targets and responsible for prion formation and propagation. Prion diseases are a group of infectious neurodegenerative diseases also known as transmissible spongiform encephalopathies. The molecular mechanisms govern the etiology of prion diseases are poorly understood. We propose to identify cellular factors that are required for prion conformational conversion and are important for subsequent stabilization of the acquired prion conformation. The success of proposed study will likely provide target genes for future drug discovery and new therapeutics for the devastating prion diseases
Keywords: Affect; Alleles; Allelomorphs; Anabolism; Animal Model; Animal Models and Related Studies; Anxiety; Biology; Bovine Spongiform Encephalopathy; CJD; CJDs (Creutzfeldt-Jakob Disease); Causality; Cells; Chaperone; Chronic Wasting Disease; Complex; Creutzfeldt-Jacob Disease; Creutzfeldt-Jakob Disease; Creutzfeldt-Jakob Syndrome; Data; Degenerative Diseases, Nervous System; Degenerative Neurologic Disorders; Development; Encephalitis, Bovine Spongiform; Encephalopathy, Bovine Spongiform; Endomycetales; Epidemic; Equilibrium; Etiology; Future; Gene Targeting; Genes; Genetic Alteration; Genetic Change; Genetic Screening; Genetic analyses; Genetic defect; Goals; HSP; Heat Shock; Heat shock proteins; Heat-Shock Reaction; Heat-Shock Response; Jakob-Creutzfeldt Disease; Light; Link; Mad Cow Disease; Maintenance; Maintenances; Microarray Analysis; Microarray-Based Analysis; Molecular; Molecular Chaperones; Molecular Configuration; Molecular Conformation; Molecular Stereochemistry; Mutation; Neurodegenerative Diseases; Neurodegenerative Disorders; Neurologic Degenerative Conditions; Neurologic Diseases, Degenerative; PSI; Phenotype; Photoradiation; Play; PrP Proteins; Prion Disease Pathway; Prion Diseases; Prion Protein Diseases; Prion Proteins; Prion-Induced Disorder; Prions; Process; Protein Structure Initiative; Protein-Folding Disease; Proteins; Publishing; Regulation; Reporting; Research; Role; S cerevisiae; Saccharomyces cerevisiae; Saccharomycetales; Spongiform Encephalopathies, Transmissible; Spongiform Encephalopathy, Subacute; Stress; Stress Proteins; Targetings, Gene; Testing; Transmissible Dementias; Variant; Variation; Wasting Disease, Chronic; Yeast, Baker`s; Yeast, Brewer`s; Yeast, Budding; Yeasts; balance; balance function; biosynthesis; conformation; conformational conversion; conformational state; conformational transition; disease causation; disease etiology; disease/disorder etiology; disorder etiology; drug discovery; gene product; genetic analysis; genome mutation; heat shock transcription factor; microarray technology; model organism; mutant; neurodegenerative illness; new therapeutics; next generation therapeutics; novel; novel therapeutics; polypeptide; prion hypothesis; protein folding; protein-only hypothesis; public health relevance; social role; spongiform degeneration; spongiform encephalopathy; success; sup35; yeast prion
Project start date: 2008-02-01
Project end date: 2011-09-29
Budget start date: 30-SEP-2009
Budget end date: 29-SEP-2011
PFA/PA: PA-07-070
3R01NS056086-02S1 (2009): $174688