Similar Publications

Gene-nutrient interaction markedly influences yeast chronological lifespan.

Exp Gerontol 2016 12 25;86:113-123. Epub 2016 Apr 25.

Nathan Shock Center of Excellence in the Basic Biology of Aging, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Comprehensive Center for Healthy Aging, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address:

Purpose: Research into the genetic mechanisms of aging has expanded rapidly over the past two decades. This has in part been the result of the use of model organisms (particularly yeast, worms and flies) and high-throughput technologies, combined with a growing interest in aging research. Despite this progress, widespread consensus regarding the pathways that are fundamental to the modulation of cellular aging and lifespan for all organisms has been limited due to discrepancies between different studies. Read More

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December 2016

Genome-wide forward genetic screens in mouse ES cells.

Methods Enzymol 2010 ;477:217-42

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.

Mouse embryonic stem (ES) cells are an attractive model system for investigating mammalian biology. Their relatively stable genome and high amenability to genome modification enables the generation of large-scale mutant libraries, which can be subsequently used for phenotype-driven genetic screens. While retroviral vectors have traditionally been used to generate insertional mutations in ES cells, their severe distribution-bias in the mammalian genome substantially limits genome-wide mutagenesis. Read More

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December 2010

Seed-effect modeling improves the consistency of genome-wide loss-of-function screens and identifies synthetic lethal vulnerabilities in cancer cells.

Genome Med 2017 06 1;9(1):51. Epub 2017 Jun 1.

Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

Background: Genome-wide loss-of-function profiling is widely used for systematic identification of genetic dependencies in cancer cells; however, the poor reproducibility of RNA interference (RNAi) screens has been a major concern due to frequent off-target effects. Currently, a detailed understanding of the key factors contributing to the sub-optimal consistency is still a lacking, especially on how to improve the reliability of future RNAi screens by controlling for factors that determine their off-target propensity.

Methods: We performed a systematic, quantitative analysis of the consistency between two genome-wide shRNA screens conducted on a compendium of cancer cell lines, and also compared several gene summarization methods for inferring gene essentiality from shRNA level data. Read More

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June 2017

Cellular and molecular modifier pathways in tauopathies: the big picture from screening invertebrate models.

J Neurochem 2016 Apr 11;137(1):12-25. Epub 2016 Feb 11.

Schaller Research Group at the University of Heidelberg and DKFZ, Proteostasis in Neurodegenerative Disease (B180), German Cancer Research Center, Heidelberg, Germany.

Abnormal tau accumulations were observed and documented in post-mortem brains of patients affected by Alzheimer's disease (AD) long before the identification of mutations in the Microtubule-associated protein tau (MAPT) gene, encoding the tau protein, in a different neurodegenerative disease called Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). The discovery of mutations in the MAPT gene associated with FTDP-17 highlighted that dysfunctions in tau alone are sufficient to cause neurodegeneration. Invertebrate models have been diligently utilized in investigating tauopathies, contributing to the understanding of cellular and molecular pathways involved in disease etiology. Read More

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April 2016