A5038876031- Fungal and yeast genetics research
- Genomics and Chromatin Dynamics
- Microbial Metabolic Engineering and Bioproduction
- DNA Repair Mechanisms
- Gene Regulatory Network Analysis
- Genetics, Aging, and Longevity in Model Organisms
- Bioinformatics and Genomic Networks
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Metabolomics and Mass Spectrometry Studies
- RNA modifications and cancer
- Bacterial biofilms and quorum sensing
- Bacterial Genetics and Biotechnology
- Advanced Proteomics Techniques and Applications
- Antifungal resistance and susceptibility
- Molecular Biology Techniques and Applications
- SARS-CoV-2 detection and testing
- Biofuel production and bioconversion
- Gut microbiota and health
- Gene expression and cancer classification
- Evolution and Genetic Dynamics
- Genetics, Bioinformatics, and Biomedical Research
- RNA and protein synthesis mechanisms
- Evolutionary Game Theory and Cooperation
- Cancer Cells and Metastasis
Stony Brook University
2005-2020
University of Toronto
2012-2020
Stony Brook University Hospital
2020
Stony Brook Medicine
2019
Donnelly College
2019
Cold Spring Harbor Laboratory
2010-2016
Cellular Research (United States)
2016
Occupational Cancer Research Centre
2016
Stony Brook School
2016
Howard Hughes Medical Institute
2013
We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and 350,000 positive interactions. This comprehensive maps interactions essential gene pairs, highlighting genes as densely connected hubs. Genetic profiles enabled assembly of hierarchical model cell function, including modules corresponding to protein complexes pathways, biological processes, cellular compartments. Negative...
Highlights•Interspecies systems biology paradigm links genetics to metabolites•Vitamin B12 is produced by the Comamonas, but not E. coli, diet•Vitamin affects development, fertility, and propionic acid toxicity•Vitamin accelerates development via SAM metabolismSummaryDiet greatly influences gene expression physiology. In mammals, elucidating effects mechanisms of individual nutrients challenging due complexity both animal its diet. Here, we used an interspecies approach with Caenorhabditis...
Significance Knowledge of oncogenic alterations that drive lung adenocarcinoma formation has enabled the development genetically engineered mouse models are increasingly being used to study biology and therapeutic vulnerabilities this disease. Given importance genomic in these processes human cancer, information on mutational landscape tumors is valuable for design interpretation experiments. In study, we compared whole-exome sequencing data from adenocarcinomas induced by different...
Many genes are regulated as an innate part of the eukaryotic cell cycle, and a complex transcriptional network helps enable cyclic behavior dividing cells. This has been studied in Saccharomyces cerevisiae (budding yeast) elsewhere. To provide more perspective on these regulatory mechanisms, we have used microarrays to measure gene expression through cycle Schizosaccharomyces pombe (fission yeast). The 750 with most significant oscillations were identified analyzed. There two broad waves...
In budding yeast, asymmetric cell division yields a larger mother and smaller daughter cell, which transcribe different genes due to the daughter-specific transcription factors Ace2 Ash1. Cell size control at Start checkpoint has long been considered be main regulator of length G1 phase cycle, resulting in longer cells. Our recent data confirmed this concept using quantitative time-lapse microscopy. However, it proposed that daughter-specific, Ace2-dependent repression expression cyclin CLN3...
Loss-of-function analyses in yeast and flies identify molecular complexes that regulate ribosomal DNA transcription.
Significance Oncometabolites are small molecules that promote tumor formation and growth. L-2-hydroxyglutarate (L-2HG) is a putative oncometabolite associated with gliomas renal cell carcinomas, as well severe neurometabolic disorder known L-2-hydroxyglutaric aciduria. However, despite L-2HG commonly considered metabolic waste product, this compound was recently discovered to control immune fate, thereby demonstrating it has endogenous functions in healthy animal cells. Here, we find the...
The Candida albicans plasma membrane plays important roles in cell growth and as a target for antifungal drugs. Analysis of Ca-Sur7 showed that this four transmembrane domain protein localized to stable punctate patches, similar the subdomains known eisosomes or MCC were discovered S. cerevisiae. localization depended on sphingolipid synthesis. In contrast cerevisiae, C. sur7Delta mutant displayed defects endocytosis morphogenesis. Septins actin mislocalized, wall synthesis was very...
Origins of DNA replication are generally inefficient, with most firing in fewer than half cell cycles. However, neither the mechanism nor importance regulation origin efficiency is clear. In fission yeast, stochastic, leading us to hypothesize that inefficiency and stochasticity result a diffusible, rate-limiting activator. We show Hsk1-Dfp1 kinase (the yeast Cdc7-Dbf4 homologue) plays such role. Increasing or decreasing levels correspondingly increases decreases efficiency. Furthermore,...
Piwi proteins and their associated small RNAs are essential for fertility in animals. In part, this is due to roles guarding germ cell genomes against the activity of mobile genetic elements. piRNA populations direct silence transposon targets and, as such, form a molecular code that discriminates transposons from endogenous genes. Information ultimately carried by piRNAs encoded within genomic loci, termed clusters. These give rise long, single-stranded, primary transcripts processed into...
The genetic basis of heritable traits has been studied for decades. Although recent mapping efforts have elucidated determinants transcript levels, protein abundance lagged. Here, we analyze levels 4084 GFP-tagged yeast proteins in the progeny a cross between laboratory and wild strain using flow cytometry high-content microscopy. genotype trans variants contributed little to level variation individual cells but explained >50% variance population’s average half GFP fusions tested. To map...
DNA synthesis is one of the landmark events in cell cycle: G1 cells have copy genome, S phase are actively engaged synthesis, and G2 twice as much nuclear cells. Cellular content can be measured by staining with a fluorescent dye followed flow-cytometric readout. This method provides quantitative measurement cycle position on cell-by-cell basis at high speed. Using flow cytometry, tens thousands single-cell measurements generated few seconds. protocol details budding yeast Saccharomyces...
The DNA replication checkpoint transcriptionally upregulates genes that allow cells to adapt and survive stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, regulates entire G(1)/S transcriptional program by directly regulating MBF, transcription factor. Instead of initiating a checkpoint-specific program, targets MBF maintain normal during We propose mechanism for this regulation, based on vitro phosphorylation Cdc10 subunit Cds1 replication-checkpoint kinase....
The amino sugar N-acetylglucosamine (GlcNAc) is known to be an important structural component of cells from bacteria humans, but its roles in cell signaling are less well understood. GlcNAc induces two pathways the human fungal pathogen Candida albicans. One activates cyclic AMP (cAMP) signaling, which stimulates formation hyphal and expression virulence genes, other pathway genes needed catabolize GlcNAc. Microarray analysis gene was carried out under four different conditions order...
Significance DNA replication and histone gene transcription are tightly linked occur during the S phase of eukaryotic cell cycle. Histone production outside is highly toxic, underscoring importance regulatory pathways that control expression. Although various regulators have been discovered, molecular mechanisms responsible for spatial temporal expression remained elusive. Here, we describe discovery Spt21 as a long-elusive cycle oscillator restricting to We show here Spt21, together with...
In S. pombe, about 5% of genes are meiosis-specific and accumulate little or no mRNA during vegetative growth. Here we use Affymetrix tiling arrays to characterize transcripts in meiotic cells. cells, many genes, especially those induced mid-meiosis, have abundant antisense transcripts. Disruption the transcription three these mid-meiotic allowed sense transcription. These results suggest that represses Although mechanism(s) mediated repression need be further explored, our data indicates...
In budding yeast, as in other eukaryotes, the Cdc7 protein kinase is important for initiation of DNA synthesis vegetative cells. addition, has crucial meiotic functions: it facilitates premeiotic replication, and essential recombination. This work uses a chemical genetic approach to demonstrate that additional roles meiosis. First, allows expression NDT80, meiosis-specific transcriptional activator required induction genes involved exit from pachytene, progression, spore formation. Second,...
In budding yeast, the replication checkpoint slows progress through S phase by inhibiting origin firing. mammals, inhibits both firing and fork movement. To find out which strategy is employed in fission Schizosaccharomyces pombe, we used microarrays to investigate use of origins wild-type checkpoint-mutant strains presence hydroxyurea (HU), limits pool deoxyribonucleoside triphosphates (dNTPs) activates checkpoint. The cells carried deletions either rad3 (which encodes yeast homologue ATR)...
Heterochromatin represents a significant portion of eukaryotic genomes and has essential structural regulatory functions. Its molecular organization is largely unknown due to difficulties in sequencing through assembling repetitive sequences enriched the heterochromatin. Here we developed novel strategy using chromosomal rearrangements embryonic phenotypes position unmapped Drosophila melanogaster heterochromatic sequence specific regions. By excluding that can be mapped assembled...
The productivity of a biological community often correlates with its diversity. In the microbial world this phenomenon can sometimes be explained by positive, density-dependent interactions such as cross-feeding and syntrophy. These metabolic help account for astonishing variety life drive many biogeochemical cycles without which we know it could not exist. While is difficult to recapitulate experimentally how these evolved among multiple taxa, explore in laboratory they arise within one....
The cell cycle of budding yeast can be arrested at specific positions by different genetic and chemical methods. These arrests enable study phase-specific phenotypes that would missed during examination asynchronous cultures. Some methods for arrest are reversible, with kinetics release cells back into a synchronous cycling state. Benefits include scalability across large range culture sizes from few milliliters to many liters, ease execution, the absence equipment requirements,...
Prior to mass spectrometric analysis, cellular small molecules must be extracted and separated from interfering components such as salts culture medium. To ensure minimal perturbation of metabolism, yeast cells grown in liquid are rapidly harvested by filtration described here. Simultaneous quenching metabolism extraction is afforded immediate immersion low-temperature organic solvent. Samples prepared using this method suitable for a range downstream chromatography-mass spectrometry...