A5072639276- Bioinformatics and Genomic Networks
- Microbial Metabolic Engineering and Bioproduction
- Fungal and yeast genetics research
- Computational Drug Discovery Methods
- Gene Regulatory Network Analysis
- Evolution and Genetic Dynamics
- Plant and Fungal Interactions Research
- Genetics, Aging, and Longevity in Model Organisms
- Amino Acid Enzymes and Metabolism
- RNA Research and Splicing
- Advanced Proteomics Techniques and Applications
- Cancer-related molecular mechanisms research
- Biomedical Text Mining and Ontologies
- Cell Image Analysis Techniques
- Gene expression and cancer classification
- Molecular Biology Techniques and Applications
- Machine Learning in Bioinformatics
- Listeria monocytogenes in Food Safety
- Fermentation and Sensory Analysis
- Biofuel production and bioconversion
- Ubiquitin and proteasome pathways
- Folate and B Vitamins Research
- Sulfur Compounds in Biology
- Chemical Reactions and Isotopes
- Pancreatitis Pathology and Treatment
The Francis Crick Institute
2017-2024
MRC Toxicology Unit
2024
University of Cambridge
2022-2024
University College London
2017-2023
Charité - Universitätsmedizin Berlin
2021-2023
Medical Research Council
2022-2023
Institute of Structural and Molecular Biology
2023
ORCID
2022
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2021
Functional genomic strategies have become fundamental for annotating gene function and regulatory networks. Here, we combined functional genomics with proteomics by quantifying protein abundances in a genome-scale knockout library Saccharomyces cerevisiae, using data-independent acquisition mass spectrometry. We find that global expression is driven complex interplay of (1) general biological properties, including translation rate, turnover, the formation complexes, growth genome...
A challenge in solving the genotype-to-phenotype relationship is to predict a cell's metabolome, believed correlate poorly with gene expression. Using comparative quantitative proteomics, we found that differential protein expression 97 Saccharomyces cerevisiae kinase deletion strains non-redundant and dominated by abundance changes metabolic enzymes. Associating enzyme landscapes corresponding metabolomes using network models provided reasoning for poor proteome-metabolome correlations;...
Metabolism is deeply intertwined with aging. Effects of metabolic interventions on aging have been explained intracellular metabolism, growth control, and signaling. Studying chronological in yeast, we reveal a so far overlooked property that influences via the exchange metabolites. We observed metabolites exported by young cells are re-imported chronologically cells, resulting cross-generational interactions. Then, used self-establishing metabolically cooperating communities (SeMeCo) as...
Abstract Genetically identical cells are known to differ in many physiological parameters such as growth rate and drug tolerance. Metabolic specialization is believed be a cause of phenotypic heterogeneity, but detection metabolically divergent subpopulations remains technically challenging. We developed proteomics-based technology, termed differential isotope labelling by amino acids (DILAC), that can detect producer consumer particular acid within an isogenic cell population monitoring...
Microbial fitness screens are a key technique in functional genomics. We present an all-in-one solution, pyphe, for automating and improving data analysis pipelines associated with large-scale screens, including image acquisition quantification, normalisation, statistical analysis. Pyphe is versatile processes from colony sizes, viability scores phloxine B staining or growth curves, all obtained inexpensive transilluminating flatbed scanners. apply pyphe to show that the information...
Abstract Cross‐feeding is fundamental to the diversity and function of microbial communities. However, identification cross‐fed metabolites often challenging due universality metabolic biosynthetic intermediates. Here, we use 13 C isotope tracing in peptides elucidate co‐cultures Saccharomyces cerevisiae Lactococcus lactis . The community was grown on lactose as main carbon source with either glucose or galactose fraction molecule labelled C. Data analysis allowing for possible mass‐shifts...
The gut microbiota is implicated in adverse effects associated with low-calorie sweeteners. Yet, the direct impact of sweeteners on bacteria remains largely uncharacterized. Here we report interactions between 25 phylogenetically diverse bacterial strains and 39 commercially used We tested these individually combination four commonly co-consumed compounds, viz., advantame, caffeine, vanillin, duloxetine. Three quarters impacted growth at least one strain. Further, over 100 were found...
Report7 September 2020Open Access Transparent process Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast Michal Malecki Corresponding Author [email protected] orcid.org/0000-0002-1525-5036 Institute Genetics and Biotechnology, Faculty Biology, University Warsaw, Poland Healthy Ageing Research Department Genetics, Evolution & Environment, College London, UK Search for more papers by this author Stephan Kamrad...
Cells balance glycolysis with respiration to support their metabolic needs in different environmental or physiological contexts. With abundant glucose, many cells prefer grow by aerobic fermentation. Using 161 natural isolates of fission yeast, we investigated the genetic basis and phenotypic effects fermentation-respiration balance. The laboratory a few other strains depended more on respiration. This trait was associated single nucleotide polymorphism conserved region Pyk1, sole pyruvate...
Ageing-related processes are largely conserved, with simple organisms remaining the main platform to discover and dissect new ageing-associated genes. Yeasts provide potent model systems study cellular ageing owing their amenability systematic functional assays under controlled conditions. Even yeast cells, however, can be laborious resource-intensive. Here we present improved experimental computational methods chronological lifespan in Schizosaccharomyces pombe. We decoded barcodes for 3206...
Many proteins remain poorly characterized even in well-studied organisms, presenting a bottleneck for research. We applied phenomics and machine-learning approaches with Schizosaccharomyces pombe broad cues on protein functions. assayed colony-growth phenotypes to measure the fitness of deletion mutants 3509 non-essential genes 131 conditions different nutrients, drugs, stresses. These analyses exposed 3492 mutants, including 124 'priority unstudied' conserved humans, providing varied...
Many proteins remain poorly characterized even in well-studied organisms, presenting a bottleneck for research. We applied phenomics and machine-learning approaches with Schizosaccharomyces pombe broad cues on protein functions. assayed colony-growth phenotypes to measure the fitness of deletion mutants 3509 non-essential genes 131 conditions different nutrients, drugs, stresses. These analyses exposed 3492 mutants, including 124 ‘priority unstudied’ conserved humans, providing varied...
Summary Metal ions play crucial roles in cells, yet the broader impact of metal availability on biological networks remains underexplored. We generated genome-wide resources, systematically quantifying yeast cell growth, metallomic, proteomic, and genetic responses upon varying each its essential (Ca, Cu, Fe, K, Mg, Mn, Mo, Na, Zn), over several orders magnitude. find that deeply cellular networks, with 57.6% proteome, including most signalling pathways, responding. While response to is...
Eukaryotic genomes express numerous long intergenic non-coding RNAs (lincRNAs) that do not overlap any coding genes. Some lincRNAs function in various aspects of gene regulation, but it is clear general to what extent contribute the information flow from genotype phenotype. To explore this question, we systematically analysed cellular roles Schizosaccharomyces pombe . Using seamless CRISPR/Cas9-based genome editing, deleted 141 lincRNA genes broadly phenotype these mutants, together with 238...
Summary Functional genomic strategies help to address the genotype phenotype problem by annotating gene function and regulatory networks. Here, we demonstrate that combining functional genomics with proteomics uncovers general principles of protein expression, provides new avenues annotate function. We recorded precise proteomes for all non-essential knock-outs in Saccharomyces cerevisiae. find abundance is driven a complex interplay i) biological properties, including translation rate,...
Cancers feature substantial intratumoral heterogeneity of genetic and phenotypically distinct lineages. Although interactions between coexisting lineages are emerging as a potential contributor to tumor evolution, the extent nature these remain largely unknown. We postulated that tumors develop ecological sustain diversity facilitate metastasis. Using combination fluorescent barcoding, mathematical modeling, metabolic analysis, in vivo models, we show Allee effect, i.e., growth dependency on...
Abstract Contamination by industrial and agricultural chemicals like pesticides are a cause of great concern due to the risk human environmental health. While these often considered have restricted activity labelled as such, there concerns over broader toxicity range. Here we report impact 1076 pollutants spanning diverse chemistries indicated applications on 22 prevalent commensal gut bacteria. Our systematic investigation uncovered 588 interactions involving 168 chemicals, majority which...
Per- and polyfluoroalkyl Substances (PFAS) - the so-called 'forever chemicals' are a major cause of environmental health concern due to their toxicity long-term persistence[1,2]. Yet, no efficient mechanisms for removal have been identified. Here we report bioaccumulation PFAS by several gut bacterial species over wide range concentrations from nanomolar up 500 μM. For bioaccumulating Bacteroides uniformis , highly prevalent species, estimate intracellular concentration in mM above that most...
Abstract When glucose is available, many organisms repress mitochondrial respiration in favour of aerobic glycolysis, or fermentation yeast, that suffices for ATP production. Fission yeast cells, however, rely partially on rapid proliferation under fermentative conditions. Here we determined the limiting factors require respiratory function during fermentation. electron transport chain was inhibited, supplementation with arginine necessary and sufficient to restore cell proliferation....
ABSTRACT Ageing-related processes are largely conserved, with simple organisms remaining the main platform to discover and dissect new ageing-associated genes. Yeasts provide potent model systems study cellular ageing owing their amenability systematic functional assays under controlled conditions. Even yeast cells, however, can be laborious resource-intensive. Here we present improved experimental computational methods chronological lifespan in Schizosaccharomyces pombe . We decoded...