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  • 1
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    Prions are a common mechanism for phenotypic inheritance in wild yeasts (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-02-18
    Description: The self-templating conformations of yeast prion proteins act as epigenetic elements of inheritance. Yeast prions might provide a mechanism for generating heritable phenotypic diversity that promotes survival in fluctuating environments and the evolution of new traits. However, this hypothesis is highly controversial. Prions that create new traits have not been found in wild strains, leading to the perception that they are rare 'diseases' of laboratory cultivation. Here we biochemically test approximately 700 wild strains of Saccharomyces for [PSI(+)] or [MOT3(+)], and find these prions in many. They conferred diverse phenotypes that were frequently beneficial under selective conditions. Simple meiotic re-assortment of the variation harboured within a strain readily fixed one such trait, making it robust and prion-independent. Finally, we genetically screened for unknown prion elements. Fully one-third of wild strains harboured them. These, too, created diverse, often beneficial phenotypes. Thus, prions broadly govern heritable traits in nature, in a manner that could profoundly expand adaptive opportunities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319070/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319070/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Halfmann, Randal -- Jarosz, Daniel F -- Jones, Sandra K -- Chang, Amelia -- Lancaster, Alex K -- Lindquist, Susan -- K99 GM098600/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Feb 15;482(7385):363-8. doi: 10.1038/nature10875.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22337056" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Evolution ; Cell Wall/metabolism ; Cytoplasm/metabolism ; Epigenesis, Genetic ; Genetic Association Studies ; Genetic Variation/genetics ; Genotype ; Heat-Shock Proteins/genetics/metabolism ; Laboratories ; Meiosis ; Peptide Termination Factors/genetics/metabolism ; *Phenotype ; Prions/genetics/*metabolism ; Saccharomyces cerevisiae/*classification/cytology/*genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Transcription Factors/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Yeast reveal a "druggable" Rsp5/Nedd4 network that ameliorates alpha-synuclein toxicity in neurons (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-10-26
    Description: alpha-Synuclein (alpha-syn) is a small lipid-binding protein implicated in several neurodegenerative diseases, including Parkinson's disease, whose pathobiology is conserved from yeast to man. There are no therapies targeting these underlying cellular pathologies, or indeed those of any major neurodegenerative disease. Using unbiased phenotypic screens as an alternative to target-based approaches, we discovered an N-aryl benzimidazole (NAB) that strongly and selectively protected diverse cell types from alpha-syn toxicity. Three chemical genetic screens in wild-type yeast cells established that NAB promoted endosomal transport events dependent on the E3 ubiquitin ligase Rsp5/Nedd4. These same steps were perturbed by alpha-syn itself. Thus, NAB identifies a druggable node in the biology of alpha-syn that can correct multiple aspects of its underlying pathology, including dysfunctional endosomal and endoplasmic reticulum-to-Golgi vesicle trafficking.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993916/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993916/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tardiff, Daniel F -- Jui, Nathan T -- Khurana, Vikram -- Tambe, Mitali A -- Thompson, Michelle L -- Chung, Chee Yeun -- Kamadurai, Hari B -- Kim, Hyoung Tae -- Lancaster, Alex K -- Caldwell, Kim A -- Caldwell, Guy A -- Rochet, Jean-Christophe -- Buchwald, Stephen L -- Lindquist, Susan -- 5R01GM069530/GM/NIGMS NIH HHS/ -- F32GM099817/GM/NIGMS NIH HHS/ -- F32NS061419/NS/NINDS NIH HHS/ -- GM58160/GM/NIGMS NIH HHS/ -- K01 AG038546/AG/NIA NIH HHS/ -- R01 GM058160/GM/NIGMS NIH HHS/ -- R15 NS075684/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Nov 22;342(6161):979-83. doi: 10.1126/science.1245321. Epub 2013 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research (WIBR), Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24158909" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Benzimidazoles/chemistry/*pharmacology ; Caenorhabditis elegans ; Cells, Cultured ; *Cytoprotection ; Drug Evaluation, Preclinical ; Endosomal Sorting Complexes Required for Transport/*genetics ; Gene Regulatory Networks/*drug effects ; Neurodegenerative Diseases/*metabolism ; Neurons/*drug effects/metabolism ; Neuroprotective Agents/*pharmacology ; Parkinson Disease/metabolism ; Rats ; Saccharomyces cerevisiae/drug effects ; Saccharomyces cerevisiae Proteins/*genetics ; Small Molecule Libraries/chemistry/pharmacology ; Ubiquitin-Protein Ligase Complexes/*genetics ; Ubiquitin-Protein Ligases/*genetics ; alpha-Synuclein/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    COSMOS: Python library for massively parallel workflows (2014)
    Oxford University Press
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    Publication Date: 2014-10-04
    Description: : Efficient workflows to shepherd clinically generated genomic data through the multiple stages of a next-generation sequencing pipeline are of critical importance in translational biomedical science. Here we present COSMOS, a Python library for workflow management that allows formal description of pipelines and partitioning of jobs. In addition, it includes a user interface for tracking the progress of jobs, abstraction of the queuing system and fine-grained control over the workflow. Workflows can be created on traditional computing clusters as well as cloud-based services. Availability and implementation: Source code is available for academic non-commercial research purposes. Links to code and documentation are provided at http://lpm.hms.harvard.edu and http://wall-lab.stanford.edu . Contact: dpwall@stanford.edu or peter_tonellato@hms.harvard.edu . Supplementary information : Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 4
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    PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition (2014)
    Oxford University Press
    Details
    Publication Date: 2014-08-27
    Description: : Prions are self-templating protein aggregates that stably perpetuate distinct biological states and are of keen interest to researchers in both evolutionary and biomedical science. The best understood prions are from yeast and have a prion-forming domain with strongly biased amino acid composition, most notably enriched for Q or N. PLAAC is a web application that scans protein sequences for domains with p rion- l ike a mino a cid c omposition. Users can upload sequence files, or paste sequences directly into a textbox. PLAAC ranks the input sequences by several summary scores and allows scores along sequences to be visualized. Text output files can be downloaded for further analyses, and visualizations saved in PDF and PNG formats. Availability and implementation: http://plaac.wi.mit.edu/ . The Ruby-based web framework and the command-line software (implemented in Java, with visualization routines in R) are available at http://github.com/whitehead/plaac under the MIT license. All software can be run under OS X, Windows and Unix. Contact: oliver.king@umassmed.edu or lindquist_admin@wi.mit.edu
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 5
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    PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition (2014)
    Oxford University Press
    Details
    Publication Date: 2014-05-13
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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