A5013973117- Bioinformatics and Genomic Networks
- Cell Image Analysis Techniques
- Computational Drug Discovery Methods
- DNA Repair Mechanisms
- Scientific Computing and Data Management
- Data Analysis with R
- Research Data Management Practices
- Microbial Natural Products and Biosynthesis
- Gene expression and cancer classification
- Pluripotent Stem Cells Research
- Fungal and yeast genetics research
- AI in cancer detection
- Gene Regulatory Network Analysis
- Antibiotic Resistance in Bacteria
- Climate Change and Health Impacts
- Spectroscopy and Chemometric Analyses
- Cancer-related Molecular Pathways
- Estrogen and related hormone effects
- Bacterial biofilms and quorum sensing
- RNA regulation and disease
- Antimicrobial Peptides and Activities
- Neurogenesis and neuroplasticity mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Prostate Cancer Treatment and Research
- ATP Synthase and ATPases Research
University of Edinburgh
2008-2023
Syngenta (United Kingdom)
2020-2022
AstraZeneca (United Kingdom)
2019-2021
AstraZeneca (Brazil)
2018
Wellcome Centre for Cell Biology
2010-2016
Institute for Research in Immunology and Cancer
2012
University of Washington
2012
Université de Montréal
2012
University of Toronto
2007-2010
Mount Sinai Hospital
2007-2010
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...
Cells respond to DNA double-strand breaks by recruiting factors such as the DNA-damage mediator protein MDC1, p53-binding 1 (53BP1), and breast cancer susceptibility BRCA1 sites of damaged DNA. Here, we reveal that ubiquitin ligase RNF8 mediates conjugation 53BP1 focal accumulation at lesions. Moreover, establish MDC1 recruits through phosphodependent interactions between forkhead-associated domain motifs in are phosphorylated activated kinase ataxia telangiectasia mutated (ATM). We also...
Article21 June 2011Open Access Cross-species discovery of syncretic drug combinations that potentiate the antifungal fluconazole Michaela Spitzer Wellcome Trust Centre for Cell Biology, School Biological Sciences, University Edinburgh, UK Search more papers by this author Emma Griffiths Michael G. DeGroote Institute Infectious Disease Research and Department Biochemistry Biomedical McMaster University, Hamilton, Ontario, Canada Smith Laboratories, British Columbia, Vancouver, Kim M Blakely...
To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series chemogenomic screens using the budding yeast Saccharomyces cerevisiae as model system. Because known human targets these drugs do not exist in yeast, could employ gene deletion collections and parallel fitness profiling to explore potential genome-wide manner. Among 214 tested, documented identified 81 compounds that inhibited wild-type growth were thus selected for profiling....
Background: Lower survival rates for many cancer types correlate with changes in nuclear size/scaling a tumor-type/tissue-specific manner. Hypothesizing that such might confer an advantage to tumor cells, we aimed at the identification of commercially available compounds guide further mechanistic studies. We therefore screened Food and Drug Administration (FDA)/European Medicines Agency (EMA)-approved reverse direction characteristic size PC3, HCT116, H1299 cell lines reflecting,...
SUMMARY Hypopigmentation is a feature of copper deficiency in humans, as caused by mutation the (Cu2+) transporter ATP7A Menkes disease, or an inability to absorb after gastric surgery. However, many causes are unknown, and genetic polymorphisms might underlie sensitivity suboptimal environmental conditions. Here, we combined phenotypic screens zebrafish for compounds that affect metabolism with yeast chemical-genetic profiles identify pathways sensitive depletion. Yeast interactions...
Vaccinia virus (VACV) is a large, cytoplasmic, double-stranded DNA that requires complex interactions with host proteins in order to replicate. To explore these functional high throughput small interfering RNA (siRNA) screen targeting 6719 druggable cellular genes was undertaken identify factors (HF) influencing the replication and spread of an eGFP-tagged VACV. The experimental design incorporated low multiplicity infection, thereby enhancing detection involved cell-to-cell revealed 153...
Yeast sulfur metabolism is transcriptionally regulated by the activator Met4. Met4 lacks DNA-binding ability and relies on interactions with Met31 Met32, paralogous proteins that bind same cis-regulatory element, to activate its targets. Although Met32 are redundant for growth in absence of methionine, studies indicate has a prominent role over when Met30, negative regulator inactive. To characterize different roles coordinating Met4-activated transcription, we examined transcription strains...
Abstract Summary: The Biological General Repository for Interaction Datasets (BioGRID) representational state transfer (REST) service allows full URL-based access to curated protein and genetic interaction data at the BioGRID database. Appending URL parameters filtering of by various attributes including gene names identifiers, PubMed ID evidence type. We also describe two visualization tools that interface with REST service, BiogridPlugin2 Cytoscape WebGraph. Availability implementation:...
In many areas of biological research, hypotheses are tested in a sequential manner, without having access to future P-values or even the number be tested. A key setting where this online hypothesis testing occurs is context publicly available data repositories, family continually growing as new accumulated over time. Recently, Javanmard and Montanari proposed first procedures that control FDR for testing. We present an R package, onlineFDR, which implements these provides wrapper functions...
Multiple signalling pathways maintain human embryonic stem cells (hESC) in an undifferentiated state. Here we sought to define the significance of G protein signal transduction preservation this state distinct from other cellular processes. Continuous treatment with drugs targeting G(αs)-, G(α-i/o)- and G(α-q/11)-subunit mediators were assessed independent hESC lines after 7days discern effects on normalised alkaline phosphatase positive colony frequency vs total cell content. This...
The network structure of biological systems suggests that effective therapeutic intervention may require combinations agents act synergistically. However, a dearth systematic chemical combination datasets have limited the development predictive algorithms for synergism. Here, we report two large linked chemical-genetic and chemical-chemical interactions in budding yeast Saccharomyces cerevisiae. We screened 5,518 unique compounds against 242 diverse gene deletion strains to generate an...
Identifying nuclei is a standard first step when analysing cells in microscopy images. The traditional approach relies on signal from DNA stain, or fluorescent transgene expression localised to the nucleus. However, imaging techniques that do not use fluorescence can also carry useful information. Here, we used brightfield and images of fixed with fluorescently labelled DNA, confirmed three convolutional neural network architectures be adapted segment channel, relying extract ground truth...
The manipulation of organisms using combinations gene knockout, RNAi and drug interaction experiments can be used to reveal regulatory interactions between genes. Several algorithms have been proposed that try reconstruct the underlying networks from expression data sets arising such experiments. Often these approaches assume each has approximately same number within network, methods rely on prior knowledge, or investigator's best guess, average network connectivity. Recent evidence points...
Abstract Summary: The MolClass toolkit and data portal generate computational models from user-defined small molecule datasets based on structural features identified in hit non-hit molecules different screens. Each new model is applied to all the database classify compound specificity. thus defines a likelihood value for each entry creates an activity fingerprint across diverse sets of uses variety machine-learning methods find molecular patterns can therefore also assign priori predictions...
Identifying nuclei is a standard first step to analysing cells in microscopy images. The traditional approach relies on signal from DNA stain, or fluorescent transgene expression localised the nucleus. However, imaging techniques that do not use fluorescence can also carry useful information. Here, we demonstrate it possible accurately segment directly brightfield images using deep learning. We confirmed three convolutional neural network architectures be adapted for this task, with U-Net...