A5006599475- Fungal and yeast genetics research
- Genetic Mapping and Diversity in Plants and Animals
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- Biofuel production and bioconversion
- Genetic and phenotypic traits in livestock
- Bacterial Genetics and Biotechnology
- Evolution and Genetic Dynamics
- Bioinformatics and Genomic Networks
- DNA and Nucleic Acid Chemistry
- Microbial Metabolic Engineering and Bioproduction
- Bacteriophages and microbial interactions
- Gene expression and cancer classification
- Glycosylation and Glycoproteins Research
- DNA Repair Mechanisms
- Escherichia coli research studies
- Animal Genetics and Reproduction
- Fermentation and Sensory Analysis
- Microbial Natural Products and Biosynthesis
- Single-cell and spatial transcriptomics
- Genetic Associations and Epidemiology
- Nanopore and Nanochannel Transport Studies
- Genetics and Plant Breeding
University of Wisconsin–Madison
2009-2025
Great Lakes Bioenergy Research Center
2017-2025
University of Wisconsin Carbone Cancer Center
2015
The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly such into high-quality, finished sequences remains challenging. Many tools are available, but they differ greatly in terms their performance (speed, scalability, hardware requirements, acceptance newer read technologies) final output (composition assembled sequence). More importantly, it largely unclear how best assess the quality sequences. Assemblathon competitions...
A finished clone-based assembly of the mouse genome reveals extensive recent sequence duplication during evolution and rodent-specific expansion certain gene families. Newly assembled duplications contain protein-coding genes that are mostly involved in reproductive function.
Abstract Targeted, genome-scale gene perturbation screens using Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) and activation (CRISPRa) have revolutionized eukaryotic genetics, advancing medical, industrial, basic research. Although CRISPRi knockdowns been broadly applied in bacteria, options for overexpression face key limitations. Here, we develop a facile approach bacteria call, “CRISPRtOE” (CRISPR transposition OverExpression). We create platform...
Rice feeds much of the world, and possesses simplest genome analyzed to date within grass family, making it an economically relevant model system for other cereal crops. Although rice is sequenced, validation gap closing efforts require purely independent means accurate finishing sequence build data.To facilitate ongoing sequencing efforts, we have constructed a whole-genome SwaI optical restriction map genome. The physical consists 14 contigs, covering 12 chromosomes, with total size 382.17...
Variation in gene copy number can alter expression and influence downstream phenotypes; thus copy-number variation provides a route for rapid evolution if the benefits outweigh cost. We recently showed that genetic background significantly influences how yeast cells respond to overexpression, revealing fitness costs of vary substantially with common-garden environment. But interplay between tolerance environment remains unexplored on genomic scale. Here, we measured overexpression four...
Significance In the last several years, we have seen significant progress toward personalized cancer genomics and therapy. Although routinely discern understand genomic variation at single base pair chromosomal levels, comprehensive analysis of genome variation, particularly structural remains a challenge. We present an integrated approach using optical mapping—a single-molecule, whole-genome system—and DNA sequencing to comprehensively identify in sequential samples from multiple myeloma...
Cellulosic plant biomass is a promising sustainable resource for generating alternative biofuels and biochemicals with microbial factories. But remaining bottleneck engineering microbes that are tolerant of toxins generated during processing, because mechanisms toxin defense only beginning to emerge. Here, we exploited natural diversity in 165 Saccharomyces cerevisiae strains isolated from diverse geographical ecological niches, identify hydrolysate-toxin tolerance. We performed genome-wide...
To cope with sudden changes in the external environment, budding yeast Saccharomyces cerevisiae orchestrates a multifaceted response that spans many levels of physiology. Several studies have interrogated transcriptome to endoplasmic reticulum (ER) stress and role regulators such as Ire1 kinase Hac1 transcription factors. However, less is known about responses ER at other Here, we used quantitative phosphoproteomics computational network inference uncover phosphoproteome reducing agent...
Bottlenecks in the efficient conversion of xylose into cost-effective biofuels have limited widespread use plant lignocellulose as a renewable feedstock. The yeast Saccharomyces cerevisiae ferments glucose ethanol with such high metabolic flux that it concentrations aerobically, trait called Crabtree/Warburg Effect. In contrast to glucose, most engineered S. strains do not ferment at economically viable rates and yields, they require respiration achieve sufficient energy return for growth...
The collection of classical inbred mouse strains displays heritable variation in a large number complex traits. Many generations historical recombination have contributed to the panel strain genomes, raising possibility that quantitative trait loci could be located with high resolution by correlating genotypes and phenotypes. Although this association mapping framework has been successful several empirical applications, its expected performance remains unclear. We used computer simulations...
Copy number variation through gene or chromosome amplification provides a route for rapid phenotypic and supports the long-term evolution of functions. Although evolutionary importance copy-number is known, little understood about how genetic background influences its tolerance. Here, we measured fitness costs over 4000 overexpressed genes in 15 Saccharomyces cerevisiae strains representing different lineages, to explore natural tolerating overexpression (OE). Strain-specific effects...
Abstract G-quadruplex (G4) structures can form in guanine-rich DNA or RNA and have been found to modulate cellular processes, including replication, transcription, translation. Many studies on the roles of G4s focused eukaryotic systems, with far fewer probing bacterial G4s. Using a chemical-genetic approach, we identified genes Escherichia coli that are important for growth G4-stabilizing conditions. Reducing levels translation elongation factor Tu slowing initiation kasugamycin,...
ABSTRACT Modern comparative genomics has been established, in part, by the sequencing and annotation of a broad range microbial species. To gain further insights, new efforts are now dealing with variety strains or isolates that gives species definition range; however, this number vastly outstrips our ability to sequence them. Given availability large species, whole genome approaches must be developed fully leverage information at level strain diversity maximize discovery. Here, we describe...
Although implicated as deleterious in many organisms, aneuploidy can underlie rapid phenotypic evolution. However, will only be maintained if the benefit outweighs cost, which remains incompletely understood. To quantify this cost and molecular determinants behind it, we generated a panel of chromosome duplications
Premature aging is a hallmark of Down syndrome, caused by trisomy human chromosome 21, but the reason unclear and difficult to study in humans. We used an aneuploid model wild yeast show that amplification disrupts nutrient-induced cell-cycle arrest, quiescence entry, healthy aging, across genetic backgrounds amplified chromosomes. discovered these defects are due part aneuploidy-induced dysfunction Ribosome Quality Control (RQC). Compared euploids, aneuploids entering display aberrant...
Significance Repeated sequences make up approximately two-thirds of the human genome, which become fully accountable when very large DNA molecules are analyzed. Long, single problematic using common experimental techniques and fluidic devices because mechanical considerations that include breakage, dealing with massive size these coils, or huge length stretched DNAs. Accordingly, we harness analyte “issues” as exploitable advantages by invention characterization “molecular gate,” controls...
Cells respond to stressful conditions by coordinating a complex, multi-faceted response that spans many levels of physiology. Much the is coordinated changes in protein phosphorylation. Although regulators transcriptome during stress are well characterized Saccharomyces cerevisiae, upstream regulatory network controlling phosphorylation less dissected. Here, we developed computational approach infer signaling regulates salt stress. We an link predicted groups likely co-regulated...
The cattle (Bos taurus) genome was originally selected for sequencing due to its economic importance and unique biology as a model organism understanding other ruminants, or mammals. Currently, there are two sequence assemblies (UMD3.1 Btau4.6) from groups using dissimilar assembly algorithms, which were complemented by genetic physical map resources. However, past comparisons between these revealed substantial differences. Consequently, such discordances have engendered ambiguities when...
Abstract CRISPR/Cas9 is a powerful tool for editing genomes, but design decisions are generally made with respect to single reference genome. With population genomic data becoming available an increasing number of model organisms, researchers interested in manipulating multiple strains and lines. CRISpy-pop web application that generates filters guide RNA sequences genome diverse yeast bacterial strains. The current implementation designs predicts the activity RNAs against more than 1000...
Identification of the genes that underlie reproductive isolation provides important insights into process speciation. According to Dobzhansky-Muller model, these suffer disrupted interactions in hybrids due independent divergence separate populations. In hybrid populations, natural selection acts remove deleterious heterospecific combinations cause functional disruptions. When is strong, this can maintain multilocus associations, primarily between conspecific alleles, providing a signature...
DNA damage and subsequent repair processes are mutagenic in nature an important driver of evolution prokaryotes, including antibiotic resistance development. Genetic screening approaches, such as transposon sequencing (Tn-seq), have provided new insights into gene function genetic relationships. Here, we employed Tn-seq to gain insight the
Although implicated as deleterious in many organisms, aneuploidy can underlie rapid phenotypic evolution. However, will only be maintained if the benefit outweighs cost, which remains incompletely understood. To quantify this cost and molecular determinants behind it, we generated a panel of chromosome duplications Saccharomyces cerevisiae applied comparative modeling validation to understand toxicity. We show that 74-94% variance aneuploid strains' growth rates is explained by additive...