A5013689370- Evolution and Genetic Dynamics
- Fungal and yeast genetics research
- Bioinformatics and Genomic Networks
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Gene Regulatory Network Analysis
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- Microbial Metabolic Engineering and Bioproduction
- Protein Structure and Dynamics
- Bacteriophages and microbial interactions
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- Biotin and Related Studies
- Advanced Fluorescence Microscopy Techniques
- Microtubule and mitosis dynamics
- Viral Infectious Diseases and Gene Expression in Insects
- Computational Drug Discovery Methods
- Alzheimer's disease research and treatments
- Plant Virus Research Studies
- Evolutionary Game Theory and Cooperation
- Antifungal resistance and susceptibility
- Genetic diversity and population structure
- Cell Image Analysis Techniques
- Chromosomal and Genetic Variations
SLAC National Accelerator Laboratory
2018-2025
Stanford University
2013-2025
Stony Brook University
2014-2020
National Institute of Standards and Technology
2018-2019
National Institute of Standards
2018
New York University
2007-2012
University of California, Santa Barbara
2005-2008
A new experimental approach reveals a bet-hedging strategy in unstressed, clonal yeast cells, whereby they adopt range of growth states that correlate with expression trehalose-synthesis regulator and predict resistance to future stress.
Regulatory and developmental systems produce phenotypes that are robust to environmental genetic variation. A gene product normally contributes this robustness is termed a phenotypic capacitor. When capacitor fails, for example when challenged by harsh environment or mutation, the system becomes less thus produces greater functional provides mechanism which hidden polymorphism can accumulate, whereas its failure evolutionary change might be promoted. The primary date of Hsp90, molecular...
The catalog of RNAs present in dendrites represents the complete repertoire local translation that contributes to synaptic plasticity. Most views hold a pool dendritic mRNAs is selectively transported destination. This view requires some dendrite are locally enriched relative cell body; however, quantitative comparisons would support this assumption do not currently exist. These issues related somatodendritic distribution also apply microRNAs, ∼21 nucleotide noncoding transcripts bind target...
Barcode sequencing (bar-seq) is a high-throughput, and cost effective method to assay large numbers of cell lineages or genotypes in complex pools. Because its advantages, applications for bar-seq are quickly growing-from using neutral random barcodes study the evolution microbes cancer, pseudo-barcodes, such as shRNAs sgRNAs simultaneously screen perturbations. However, computational pipelines clustering not well developed. Available methods often yield high frequency under-clustering...
Copy number variants (CNVs) are a pervasive source of genetic variation and evolutionary potential, but the dynamics diversity CNVs within evolving populations remain unclear. Long-term evolution experiments in chemostats provide an ideal system for studying molecular processes underlying CNV formation temporal with which they generated, selected, maintained. Here, we developed fluorescent reporter to detect de novo gene amplifications deletions individual cells. We used Saccharomyces...
Article30 March 2021Open Access Source DataTransparent process The genotype-phenotype landscape of an allosteric protein Drew S Tack orcid.org/0000-0002-9380-4643 National Institute Standards and Technology, Gaithersburg, MD, USA Search for more papers by this author Peter D Tonner orcid.org/0000-0003-2840-0930 Abe Pressman Nathan Olson orcid.org/0000-0003-2585-3037 Sasha F Levy orcid.org/0000-0002-0923-1636 SLAC Accelerator Laboratory, Menlo Park, CA, Joint Initiative Metrology in Biology,...
In diploid species, genetic loci can show additive, dominance, and epistatic effects. To characterize the contributions of these different types effects to heritable traits, we use a double barcoding system generate phenotype panel ~200,000 yeast strains that be partitioned into hundreds interrelated families. This experiment enables detection thousands loci, many whose vary across Here, traits are largely specified by small number hub with major additive dominance effects, pervasive...
The microtubule-associated protein tau is implicated in the pathogenesis of many neurodegenerative diseases, including fronto-temporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), which both RNA splicing amino acid substitution mutations cause dominantly inherited early onset dementia. RNA-splicing FTDP-17 alter wild-type approximately 50:50 3-repeat (3R) 4-repeat (4R) isoform ratio, usually resulting an excess 4R tau. To examine further how might dysfunction by misregulation...
The low costs of array-synthesized oligonucleotide libraries are empowering rapid advances in quantitative and synthetic biology. However, high synthesis error rates, uneven representation, lack access to individual oligonucleotides limit the true potential these libraries. We have developed a cost-effective method called Recombinase Directed Indexing (REDI), which involves integration complex library into yeast, site-specific recombination index DNA, next-generation sequencing identify...
Protein-Protein Interactions (PPIs) are a key interface between virus and host, these interactions important to both viral reprogramming of the host restriction infection. In particular, viral-host PPI networks can be used further our understanding molecular mechanisms tissue specificity, range, virulence. At higher scales, screening could also screen for small-molecule antivirals that interfere with essential interactions, or explore how interacting genomes co-evolve. Current...
Biological systems produce phenotypes that appear to be robust perturbation by mutations and environmental variation. Prior studies identified genes that, when impaired, reveal previously cryptic genetic This result is typically interpreted as evidence the disrupted gene normally increases robustness mutations, such would allow variants accumulate. However, revelation of variation not necessarily a mutationally state has been made less robust. Demonstrating difference in requires comparing...
The acquisition of new genes, via horizontal transfer or gene duplication/diversification, has been the dominant mechanism thus far implicated in evolution microbial pathogenicity. In contrast, role many other modes evolution--such as changes expression regulation-remains unknown. A transition to a pathogenic lifestyle recently taken place some lineages budding yeast Saccharomyces cerevisiae. Here we identify module physically interacting proteins involved endocytosis that experienced...
Abstract Several large-scale efforts have systematically catalogued protein-protein interactions (PPIs) of a cell in single environment. However, little is known about how the protein interactome changes across environmental perturbations. Current technologies, which assay one PPI at time, are too low throughput to make it practical study dynamics. Here, we develop highly parallel interaction sequencing (PPiSeq) platform that uses novel double barcoding system conjunction with dihydrofolate...
Large-scale genetic interaction (GI) screens in yeast have been invaluable for our understanding of molecular systems biology and characterizing novel gene function. Owing part to the high costs long experiment times required, a preponderance GI data has generated single environmental condition. However, an unknown fraction GIs may be specific other conditions. Here, we developed pooled-growth CRISPRi-based sequencing assay GIs, CRISPRiSeq, which increases throughput such that can easily...
Abstract Interactions between genetic perturbations and segregating loci can cause to show different phenotypic effects across genetically distinct individuals. To study these interactions on a genome scale in many individuals, we used combinatorial DNA barcode sequencing measure the fitness of 8046 CRISPRi targeting 1721 genes 169 yeast cross progeny (or segregants). We identified 460 whose perturbation has segregants. Several factors caused variable effects, including baseline segregant...
Mutations affecting either the structure or regulation of microtubule-associated protein Tau cause neuronal cell death and dementia. However, molecular mechanisms mediating these deleterious effects remain unclear. Among most characterized activities is ability to regulate microtubule dynamics, known be essential for proper function viability. Here we have tested hypothesis that mutations causing neurodegeneration also alter dynamic instability behaviors microtubules. Using in vitro dynamics...
Systematic screens for genetic interactions are a cornerstone of both network and systems biology. However, most have been limited to characterizing interaction networks in single environment. Moving beyond this static view the cell requires major technological advance increase throughput ease replication these assays. Here, we introduce iSeq-a platform build large double barcode libraries rapidly assay across environments. We use iSeq yeast measure fitness three conditions nearly 400 clonal...