A5027866777- Fungal and yeast genetics research
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Microbial Natural Products and Biosynthesis
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Microbial Metabolic Engineering and Bioproduction
- Computational Drug Discovery Methods
- DNA Repair Mechanisms
- Molecular Biology Techniques and Applications
- Cancer therapeutics and mechanisms
- Evolution and Genetic Dynamics
- Gene Regulatory Network Analysis
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- Genetics, Aging, and Longevity in Model Organisms
- Viral Infectious Diseases and Gene Expression in Insects
- Biofuel production and bioconversion
- Mitochondrial Function and Pathology
- Plant-Microbe Interactions and Immunity
- DNA and Nucleic Acid Chemistry
- Antifungal resistance and susceptibility
- Genetic Mapping and Diversity in Plants and Animals
- Advanced biosensing and bioanalysis techniques
University of British Columbia
2015-2024
University of Toronto
2007-2016
Canada Research Chairs
2008-2012
University of New Brunswick
2008-2012
Stanford University
1999-2011
Lawrence Berkeley National Laboratory
2010
Palo Alto University
2010
Mount Sinai Hospital
2008
Lunenfeld-Tanenbaum Research Institute
2008
University of California, Berkeley
2005-2008
The functions of many open reading frames (ORFs) identified in genome-sequencing projects are unknown. New, whole-genome approaches required to systematically determine their function. A total 6925 Saccharomyces cerevisiae strains were constructed, by a high-throughput strategy, each with precise deletion one 2026 ORFs (more than one-third the genome). Of deleted ORFs, 17 percent essential for viability rich medium. phenotypes more 500 assayed parallel. strains, 40 showed quantitative growth...
A genome-scale genetic interaction map was constructed by examining 5.4 million gene-gene pairs for synthetic interactions, generating quantitative profiles approximately 75% of all genes in the budding yeast, Saccharomyces cerevisiae. network based on reveals a functional cell which similar biological processes cluster together coherent subsets, and highly correlated delineate specific pathways to define gene function. The global identifies cross-connections between bioprocesses, mapping...
Genetics aims to understand the relation between genotype and phenotype. However, because complete deletion of most yeast genes ( approximately 80%) has no obvious phenotypic consequence in rich medium, it is difficult study their functions. To uncover phenotypes for this nonessential fraction genome, we performed 1144 chemical genomic assays on whole-genome heterozygous homozygous collections quantified growth fitness each strain presence or environmental stress conditions. We found that...
Haploinsufficiency is defined as a dominant phenotype in diploid organisms that are heterozygous for loss-of-function allele. Despite its relevance to human disease, neither the extent of haploinsufficiency nor precise molecular mechanisms well understood. We used complete set Saccharomyces cerevisiae deletion strains survey genome via fitness profiling rich (YPD) and minimal media identify all genes confer haploinsufficient growth defect. This assay revealed approximately 3% 5900 tested...
We demonstrate the efficacy of a genome-wide protocol in yeast that allows identification those gene products functionally interact with small molecules and result inhibition cellular proliferation. Here we present results from screening 10 diverse compounds 80 experiments against complete collection heterozygous deletion strains. These include anticancer antifungal agents, statins, alverine citrate, dyclonine. In several cases, identified previously known interactions; furthermore, each...
Sometimes mutations in two genes produce a phenotype that is surprising light of each mutation's individual effects. This phenomenon, which defines genetic interaction, can reveal functional relationships between and pathways. For example, double mutants with surprisingly slow growth define synergistic interactions identify compensatory pathways or protein complexes. Recent studies have used four mathematically distinct definitions interaction (here termed Product, Additive, Log, Min)....
All organisms have elaborate mechanisms to control rates of protein production. However, production is also subject stochastic fluctuations, or "noise." Several recent studies in Saccharomyces cerevisiae and Escherichia coli investigated the relationship between transcription translation fluctuations levels, more generally, how such randomness a function intrinsic extrinsic factors. fundamental question whether stochasticity expression generally biologically relevant has not been addressed,...
We generated a high-resolution whole-genome sequence and individually deleted 5100 genes in Sigma1278b, Saccharomyces cerevisiae strain closely related to reference S288c. Similar the variation between human individuals, Sigma1278b S288c average 3.2 single-nucleotide polymorphisms per kilobase. A genome-wide comparison of deletion mutant phenotypes identified subset that were conditionally essential by strain, including 44 unique 13 Genetic analysis indicates conditional phenotype was most...
Next-generation DNA sequencing technologies have revolutionized diverse genomics applications, including de novo genome sequencing, SNP detection, chromatin immunoprecipitation, and transcriptome analysis. Here we apply deep to genome-scale fitness profiling evaluate yeast strain collections in parallel. This method, Barcode analysis by Sequencing, or "Bar-seq," outperforms the current benchmark barcode microarray assay terms of both dynamic range throughput. When applied a complex...
Yeasty HIPHOP In order to identify how chemical compounds target genes and affect the physiology of cell, tests perturbations that occur when treated with a range pharmacological chemicals are required. By examining haploinsufficiency profiling (HIP) homozygous (HOP) chemogenomic platforms, Lee et al. (p. 208 ) analyzed response yeast thousands different small molecules, genetic, proteomic, bioinformatic analyses. Over 300 were identified targeted 121 within 45 cellular signature networks....
Abstract Parasitic nematodes infect one quarter of the world’s population and impact all humans through widespread infection crops livestock. Resistance to current anthelmintics has prompted search for new drugs. Traditional screens that rely on parasitic worms are costly labour intensive target-based approaches have failed yield novel anthelmintics. Here, we present our screen 67,012 compounds identify those kill non-parasitic nematode Caenorhabditis elegans . We then rescreen hits in two...
The dimorphic switch from a single-cell budding yeast to filamentous form enables Saccharomyces cerevisiae forage for nutrients and the opportunistic pathogen Candida albicans invade human tissues evade immune system. We constructed genome-wide set of targeted deletion alleles introduced them into S. strain, Σ1278b. identified genes involved in morphologically distinct forms filamentation: haploid invasive growth, biofilm formation, diploid pseudohyphal growth. Unique appear underlie each...
The evolutionary rates of proteins vary over several orders magnitude. Recent work suggests that analysis large data sets in conjunction with the results from high-throughput functional genomic experiments can identify factors cause to evolve at such dramatically different rates. To this end, we estimated >3,000 four species yeast genus Saccharomyces and investigated their relationship levels expression protein dispensability. Each protein's dispensability was by growth rate mutants...