SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Warringer Jonas 1973) "

Sökning: WFRF:(Warringer Jonas 1973)

  • Resultat 1-50 av 92
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Molin, Mikael, 1973, et al. (författare)
  • Protein kinase A controls yeast growth in visible light
  • 2020
  • Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A wide variety of photosynthetic and non-photosynthetic species sense and respond to light, having developed protective mechanisms to adapt to damaging effects on DNA and proteins. While the biology of UV light-induced damage has been well studied, cellular responses to stress from visible light (400–700 nm) remain poorly understood despite being a regular part of the life cycle of many organisms. Here, we developed a high-throughput method for measuring growth under visible light stress and used it to screen for light sensitivity in the yeast gene deletion collection. Results: We found genes involved in HOG pathway signaling, RNA polymerase II transcription, translation, diphthamide modifications of the translational elongation factor eEF2, and the oxidative stress response to be required for light resistance. Reduced nuclear localization of the transcription factor Msn2 and lower glycogen accumulation indicated higher protein kinase A (cAMP-dependent protein kinase, PKA) activity in many light-sensitive gene deletion strains. We therefore used an ectopic fluorescent PKA reporter and mutants with constitutively altered PKA activity to show that repression of PKA is essential for resistance to visible light. Conclusion: We conclude that yeast photobiology is multifaceted and that protein kinase A plays a key role in the ability of cells to grow upon visible light exposure. We propose that visible light impacts on the biology and evolution of many non-photosynthetic organisms and have practical implications for how organisms are studied in the laboratory, with or without illumination.
  •  
2.
  • Ahmadpour, Doryaneh, 1973, et al. (författare)
  • Robustness analysis of HOG pathway genes in Saccharomyces cerevisiae
  • 2006
  • Ingår i: YSBN Meeting Nov. 14-16, 2006- Vienna- Austria.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Robustness analysis of HOG pathway genes in Saccharomyces cerevisiae Doryaneh Ahmadpour1, Lars-Göran Ottosson1, Markus Krantz2, Jonas Warringer1, Anders Blomberg1 and Stefan Hohmann1* 1Department of Cell and Molecular Biology/Microbiology, Göteborg University, S-405 30 Göteborg, Sweden 2 The Systems Biology Institute (SBI), Shibuya, Tokyo, Japan E-mail: doryaneh.ahmadpour@gmm.gu.se Robustness is a fundamental property of biological systems and crucial for their effective function under internal or external perturbations. For instance, it has been proposed that internal parameters such as gene expression have been optimized during evolution such that a given system has the observed robustness. The permissible ranges of internal parameters in the cells are not comprehensively understood since there has not been a technique to measure such parameters. “Genetic tug-of-war” (gTOW) [1] is a genetic screening method that allows the investigation of the upper limit copy number of genes, and thereby the upper permissible range of gene expression level. This method is based on a 2-micron plasmid vector containing the leu2d allele with a very weak complementation activity and the gene of interest inserted as target gene. When the leu2ura3 deletion yeast cells transformed with pTOW plasmid are cultured under leucine-limiting conditions, there will be a bias toward increasing the plasmid copy number to compensate for the lack of leucine. On the other hand there will be an opposing bias toward decreasing the plasmid copy number if the target gene inhibits growth or has a toxic effect when a certain copy number is exceeded (it reaches to its upper limit). Eventually as a result of the “tug-of-war” between these two selection biases cells with optimized plasmid copy number will be concentrated. In this study we have applied the gTOW method on 29 HOG pathway related genes in Saccharomyces cerevisiae. The high osmolarity glycerol (HOG) MAPK pathway is essential for yeast survival in high osmolarity condition and consists of two branches that activate a MAPK (Hog1) via a MAPKK (Pbs2) to orchestrate part of the transcriptional response. The HOG pathway is the best understood osmoresponsive system in eukaryotes and the quantitative data provided by the gTOW method collating with the existing computational models could be used to analyze the robustness and fragility of the pathway. 1. Hisao Moriya, Yuki Shimizu-Yoshida and Hiroaki Kitano, 2006, PLoS Genetics, 2:7
  •  
3.
  • Ahmadpour, Doryaneh, 1973, et al. (författare)
  • Robustness analysis of HOG pathway related genes in Saccharomyces cerevisiae
  • 2007
  • Ingår i: FEBS-SysBio March 10-16, 2007- Gosau, Austria.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Robustness analysis of HOG pathway related genes in Saccharomyces cerevisiae Doryaneh Ahmadpour1, Lars-Göran Ottosson1, Markus Krantz2, Jonas Warringer1, Anders Blomberg1 and Stefan Hohmann1* 1Department of Cell and Molecular Biology/Microbiology, Göteborg University, S-405 30 Göteborg, Sweden 2 The Systems Biology Institute (SBI), Shibuya, Tokyo, Japan E-mail: doryaneh.ahmadpour@gmm.gu.se Robustness is a fundamental property of biological systems and crucial for their effective function under internal or external perturbations. For instance, it has been proposed that internal parameters such as gene expression have been optimized during evolution such that a given system has the observed robustness. The permissible ranges of internal parameters in the cells are not comprehensively understood since there has not been a technique to measure such parameters. “Genetic tug-of-war” (gTOW) [1] is a genetic screening approach that allows the determination of the upper limit copy number of genes, and thereby the upper permissible range of the level of gene expression. This method is based on a 2-micron plasmid vector containing the LEU2d allele with a very weak complementation activity and the gene of interest inserted as target gene. When the leu2 ura3 mutant yeast transformed with pTOW plasmids is cultured under leucine-limiting conditions, there will be a bias toward increasing the plasmid copy number to satisfy the requirement for leucine. On the other hand there will be an opposing bias toward decreasing the plasmid copy number if the target gene inhibits growth when a certain copy number is exceeded (i.e. it reaches its upper limit). Eventually as a result of the “tug-of-war” between these two selection biases cells with optimized plasmid copy number will accumulate. In this study we have applied the gTOW method on 29 HOG pathway genes in S. cerevisiae. The high osmolarity glycerol (HOG) MAPK pathway is essential for yeast survival in high osmolarity condition [2]. It consists of two branches that activate a MAPK (Hog1) to orchestrate part of the transcriptional response. The HOG pathway is the best understood osmoresponsive system in eukaryotes. The quantitative data provided by the gTOW method collating with the existing computational models [3] could be used to analyze the robustness and fragility of the pathway. 1. Moriya H, et al., (2006), PLoS Genet 2(7): e111 2. Hohmann S (2002), Microbiol Mol Biol Rev 66:300 3. Klipp E, et al., (2005), Nat Biotechnol 23:975
  •  
4.
  • Alalam, Hanna, et al. (författare)
  • A High-Throughput Method for Screening for Genes Controlling Bacterial Conjugation of Antibiotic Resistance.
  • 2020
  • Ingår i: mSystems. - 2379-5077. ; 5:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The rapid horizontal transmission of antibiotic resistance genes on conjugative plasmids between bacterial host cells is a major cause of the accelerating antibiotic resistance crisis. There are currently no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation, which prevents understanding and targeting conjugation. We introduce a novel experimental framework to screen for conjugation-based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. Plasmid-carrying donor strains are constructed in high-throughput. We then mix the resistance plasmid-carrying donors with recipients in a design where only transconjugants can reproduce, measure growth in dense intervals, and extract transmission times as the growth lag. As proof-of-principle, we exhaustively explore chromosomal genes controlling F-plasmid donation within Escherichia coli populations, by screening the Keio deletion collection in high replication. We recover all seven known chromosomal gene mutants affecting conjugation as donors and identify many novel mutants, all of which diminish antibiotic resistance transmission. We validate nine of the novel genes' effects in liquid mating assays and complement one of the novel genes' effect on conjugation (rseA). The new framework holds great potential for exhaustive disclosing of candidate targets for helper drugs that delay resistance development in patients and societies and improve the longevity of current and future antibiotics. Further, the platform can easily be adapted to explore interspecies conjugation, plasmid-borne factors, and experimental evolution and be used for rapid construction of strains.IMPORTANCE The rapid transmission of antibiotic resistance genes on conjugative plasmids between bacterial host cells is a major cause of the accelerating antibiotic resistance crisis. There are currently no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation, which prevents understanding and targeting conjugation. We introduce a novel experimental framework to screen for conjugation-based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. As proof-of-principle, we exhaustively explore chromosomal genes controlling F-plasmid donation within E. coli populations. We recover all previously known and many novel chromosomal gene mutants that affect conjugation efficiency. The new framework holds great potential for rapid screening of compounds that decrease transmission. Further, the platform can easily be adapted to explore interspecies conjugation, plasmid-borne factors, and experimental evolution and be used for rapid construction of strains.
  •  
5.
  • Barré, Benjamin P., et al. (författare)
  • Intragenic repeat expansion in the cell wall protein gene HPF1 controls yeast chronological aging
  • 2020
  • Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 30:5, s. 697-710
  • Tidskriftsartikel (refereegranskat)abstract
    • Aging varies among individuals due to both genetics and environment, but the underlying molecular mechanisms remain largely unknown. Using a highly recombined Saccharomyces cerevisiae population, we found 30 distinct quantitative trait loci (QTLs) that control chronological life span (CLS) in calorie-rich and calorie-restricted environments and under rapamycin exposure. Calorie restriction and rapamycin extended life span in virtually all genotypes but through different genetic variants. We tracked the two major QTLs to the cell wall glycoprotein genes FLO11 and HPF1. We found that massive expansion of intragenic tandem repeats within the N-terminal domain of HPF1 was sufficient to cause pronounced life span shortening. Life span impairment by HPF1 was buffered by rapamycin but not by calorie restriction. The HPF1 repeat expansion shifted yeast cells from a sedentary to a buoyant state, thereby increasing their exposure to surrounding oxygen. The higher oxygenation altered methionine, lipid, and purine metabolism, and inhibited quiescence, which explains the life span shortening. We conclude that fast-evolving intragenic repeat expansions can fundamentally change the relationship between cells and their environment with profound effects on cellular lifestyle and longevity.
  •  
6.
  • Caesar, Robert, 1973, et al. (författare)
  • Physiological importance and identification of novel targets for the N-terminal acetyltransferase NatB
  • 2006
  • Ingår i: Eukaryotic Cell. - 1535-9778. ; 5:2, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • The N-terminal acetyltransferase NatB in Saccharomyces cerevisiae consists of the catalytic subunit Nat3p and the associated subunit Mdm20p. We here extend our present knowledge about the physiological role of NatB by a combined proteomics and phenomics approach. We found that strains deleted for either NAT3 or MDM20 displayed different growth rates and morphologies in specific stress conditions, demonstrating that the two NatB subunits have partly individual functions. Earlier reported phenotypes of the nat3{Delta} strain have been associated with altered functionality of actin cables. However, we found that point mutants of tropomyosin that suppress the actin cable defect observed in nat3{Delta} only partially restores wild-type growth and morphology, indicating the existence of functionally important acetylations unrelated to actin cable function. Predicted NatB substrates were dramatically overrepresented in a distinct set of biological processes, mainly related to DNA processing and cell cycle progression. Three of these proteins, Cac2p, Pac10p, and Swc7p, were identified as true NatB substrates. To identify N-terminal acetylations potentially important for protein function, we performed a large-scale comparative phenotypic analysis including nat3{Delta} and strains deleted for the putative NatB substrates involved in cell cycle regulation and DNA processing. By this procedure we predicted functional importance of the N-terminal acetylation for 31 proteins.
  •  
7.
  • Ericson, Elke, 1973, et al. (författare)
  • Genetic pleiotropy in Saccharomyces cerevisiae quantified by high-resolution phenotypic profiling
  • 2006
  • Ingår i: Molecular Genetics and Genomics. - : Springer Science and Business Media LLC. - 1617-4615 .- 1617-4623. ; 275:6, s. 605-614
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic pleiotropy, the ability of a mutation in a single gene to give rise to multiple phenotypic outcomes, constitutes an important but incompletely understood biological phenomenon. We used a highresolution and high-precision phenotypic profiling approach to quantify the fitness contribution of genes on the five smallest yeast chromosomes during different forms of environmental stress, selected to probe a wide diversity of physiological features. We found that the extent of pleiotropy is much higher than previously claimed; 17% of the yeast genes were pleiotropic whereof one-fifth were hyper-pleiotropic. Pleiotropic genes preferentially participate in functions related to determination of protein fate, cell growth and morphogenesis, signal transduction and transcription. Contrary to what has earlier been proposed we did not find experimental evidence for slower evolutionary rate of pleiotropic genes/proteins. We also refute the existence of phenotypic islands along chromosomes but report on a remarkable loss both of pleiotropy and of phenotypic penetrance towards chromosomal ends. Thus, the here reported features of pleiotropy both have implications on our understanding of evolutionary processes as well as the mechanisms underlying disease.
  •  
8.
  • Fernandez-Ricaud, Luciano, 1975, et al. (författare)
  • PROPHECY - a database for high-resolution phenomics
  • 2005
  • Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 33
  • Tidskriftsartikel (refereegranskat)abstract
    • The rapid recent evolution of the field phenomics—the genome-wide study of gene dispensability by quantitative analysis of phenotypes—has resulted in an increasing demand for new data analysis and visualization tools. Following the introduction of a novel approach for precise, genome-wide quantification of gene dispensability in Saccharomyces cerevisiae we here announce a public resource for mining, filtering and visualizing phenotypic data—the PROPHECY database. PROPHECY is designed to allow easy and flexible access to physiologically relevant quantitative data for the growth behaviour of mutant strains in the yeast deletion collection during conditions of environmental challenges. PROPHECY is publicly accessible at http://prophecy.lundberg.gu.se.
  •  
9.
  • Fernandez-Ricaud, Luciano, 1975, et al. (författare)
  • PROPHECY—a yeast phenome database, update 2006
  • 2007
  • Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 35
  • Tidskriftsartikel (refereegranskat)abstract
    • Connecting genotype to phenotype is fundamental in biomedical research and in our understanding of disease. Phenomics—the large-scale quantitative phenotypic analysis of genotypes on a genome-wide scale—connects automated data generation with the development of novel tools for phenotype data integration, mining and visualization. Our yeast phenomics database PROPHECY is available at http://prophecy.lundberg.gu.se. Via phenotyping of 984 heterozygous diploids for all essential genes the genotypes analysed and presented in PROPHECY have been extended and now include all genes in the yeast genome. Further, phenotypic data from gene overexpression of 574 membrane spanning proteins has recently been included. To facilitate the interpretation of quantitative phenotypic data we have developed a new phenotype display option, the Comparative Growth Curve Display, where growth curve differences for a large number of mutants compared with the wild type are easily revealed. In addition, PROPHECY now offers a more informative and intuitive first-sight display of its phenotypic data via its new summary page. We have also extended the arsenal of data analysis tools to include dynamic visualization of phenotypes along individual chromosomes. PROPHECY is an initiative to enhance the growing field of phenome bioinformatics
  •  
10.
  • Forsmark, Annabelle, 1973, et al. (författare)
  • Quantitative Proteomics of Yeast Post-Golgi Vesicles Reveals a Discriminating Role for Sro7p in Protein Secretion
  • 2011
  • Ingår i: Traffic. - : John Wiley & Sons. - 1398-9219 .- 1600-0854. ; 12:6, s. 740-753
  • Tidskriftsartikel (refereegranskat)abstract
    • We here report the first comparative proteomics of purified yeast post-Golgi vesicles (PGVs). Vesicle samples isolated from PGV-accumulating sec6-4 mutants were treated with isobaric tags (iTRAQ) for subsequent quantitative tandem mass spectrometric analysis of protein content. After background subtraction, a total of 66 vesicle-associated proteins were identified, including known or assumed vesicle residents as well as a fraction not previously known to be PGV associated. Vesicles isolated from cells lacking the polarity protein Sro7p contained essentially the same catalogue of proteins but showed a reduced content of a subset of cargo proteins, in agreement with a previously shown selective role for Sro7p in cargo sorting.
  •  
11.
  • Gombault, Aurélie, et al. (författare)
  • A phenotypic study of TFS1 mutants differentially altered in the inhibition of Ira2p or CPY.
  • 2009
  • Ingår i: FEMS yeast research. - : Oxford University Press (OUP). - 1567-1364 .- 1567-1356. ; 9:6, s. 867-74
  • Tidskriftsartikel (refereegranskat)abstract
    • The Saccharomyces cerevisiae protein Tfs1p is known as a dual protein. On the one hand, it inhibits the carboxypeptidase Y protease, and on the other, it inhibits Ira2p, a GTPase-activating protein of Ras. We managed to dissect precise areas of Tfs1p specifically involved in only one of those functions. Based on these data, specific Tfs1p point mutants affected in only one of these two functions were constructed. In order to obtain insights on the physiological role of these functions, systematic phenotypic tests were performed on strains expressing these specific Tfs1p mutants. The results obtained demonstrate that the inhibition of Ira2p by Tfs1p is the predominant function under the conditions tested.
  •  
12.
  • Jansson, Kristina, 1969, et al. (författare)
  • A role for Myh1 in DNA repair after treatment with strand-breaking and crosslinking chemotherapeutic agents
  • 2013
  • Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 0893-6692 .- 1098-2280. ; 54:5, s. 327-337
  • Tidskriftsartikel (refereegranskat)abstract
    • The highly conserved DNA glycosylase MutY is implicated in repair of oxidative DNA damage, in particular in removing adenines misincorporated opposite 7,8-dihydro-8-oxoguanine (8-oxo-G). The MutY homologues (MutYH) physically associate with proteins implicated in replication, DNA repair, and checkpoint signaling, specifically with the DNA damage sensor complex 9-1-1 proteins. Here, we ask whether MutYH could have a broader function in sensing and repairing different types of DNA damage induced by conventional chemotherapeutics. Thus, we examined if deletion of the Schizosaccharomyces pombe MutY homologue, Myh1, alone or in combination with deletion of either component of the 9-1-1 sensor complex, influences survival after exposure to different classes of DNA damaging chemotherapeutics that do not act primarily by causing 8-oxoG lesions. We show that Myh1 contributes to survival on genotoxic stresses induced by the oxidizing, DNA double strand break-inducing, bleomycins, or the DNA crosslinking platinum compounds, particularly in a rad1 mutant background. Exposure of cells to cisplatin leads to a moderate overall accumulation of Myh1 protein. Interestingly, we found that DNA damage induced by phleomycin results in increased chromatin association of Myh1. Further, we demonstrate that Myh1 relocalizes to the nucleus after exposure to hydrogen peroxide or chemotherapeutics, most prominently seen after phleomycin treatment. These observations indicate a wider role of Myh1 in DNA repair and DNA damage-induced checkpoint activation than previously thought
  •  
13.
  • Kohler, A., et al. (författare)
  • High-throughput biochemical fingerprinting of Saccharomyces cerevisiae by Fourier transform infrared spectroscopy
  • 2015
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Single-channel optical density measurements of population growth are the dominant large scale phenotyping methodology for bridging the gene-function gap in yeast. However, a substantial amount of the genetic variation induced by single allele, single gene or double gene knock-out technologies fail to manifest in detectable growth phenotypes under conditions readily testable in the laboratory. Thus, new high-throughput phenotyping technologies capable of providing information about molecular level consequences of genetic variation are sorely needed. Here we report a protocol for high-throughput Fourier transform infrared spectroscopy (FTIR) measuring biochemical fingerprints of yeast strains. It includes high-throughput cultivation for FTIR spectroscopy, FTIR measurements and spectral pretreatment to increase measurement accuracy.We demonstrate its capacity to distinguish not only yeast genera, species and populations, but also strains that differ only by a single gene, its excellent signal-to-noise ratio and its relative robustness to measurement bias. Finally, we illustrated its applicability by determining the FTIR signatures of all viable Saccharomyces cerevisiae single gene knock-outs corresponding to lipid biosynthesis genes. Many of the examined knock-out strains showed distinct, highly reproducible FTIR phenotypes despite having no detectable growth phenotype. These phenotypes were confirmed by conventional lipid analysis and could be linked to specific changes in lipid composition. We conclude that the introduced protocol is robust to noise and bias, possible to apply on a very large scale, and capable of generating biologically meaningful biochemical fingerprints that are strain specific, even when strains lack detectable growth phenotypes. Thus, it has a substantial potential for application in the molecular functionalization of the yeast genome.
  •  
14.
  • Krantz, Marcus, 1975, et al. (författare)
  • Robustness and fragility in the high osmolarity glycerol (HOG) pathway in S. cerevisiae
  • 2009
  • Ingår i: 10th International Conference on Systems Biology (ICSB2009) proceedings, 10th International Conference on Systems Biology (ICSB2009), Aug 30 - Sep 4, Stanford, California, USA.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Cellular signalling networks integrate environmental stimuli with information on cellular status. These networks must be robust against stochastic fluctuations in external stimuli as well as in the amounts of signalling components. Here [1], we challenge the yeast HOG signal transduction pathway with systematic perturbations in components’ expression levels implemented by a “genetic tug-of-war” methodology under various external conditions in search of nodes of fragilities. We observe a substantially higher frequency of fragile nodes in this signal transduction pathway than has been observed for other cellular processes. These fragilities disperse without any clear pattern over biochemical functions or location in pathway topology, with the most sensitive nodes being the proteins PBS2 and SSK1. They are also largely independent of pathway activation by external stimuli. However, the strongest toxicities are caused by pathway hyperactivation. We studied the influence of seven regulatory motifs around these HOG pathway components in silico through ODE models. Based on the SLN1 and the MAPK modules of a mathematical model of osmoregulation in budding yeast by Klipp et al. [2] we included new motifs and fitted the affected parameters to time courses of dually phosphorylated Hog1p generated by the original model under stress and stress-free conditions. The regulations taken into account by our analysis include Pbs2p scaffolding, Ssk1p and Pbs2p autoactivation, and the formation of a stable dimer between Ssk2p and Ssk1p. A subsequent sensitivity analysis identified Pbs2's role as a scaffold protein and Ssk1p-Ssk2p dimerization as the important contributors to the observed robustness pattern in silico. Thus, in vivo robustness data can be used to discriminate and improve mathematical models.
  •  
15.
  • Krantz, Marcus, 1975, et al. (författare)
  • Robustness and fragility in the yeast high osmolarity glycerol (HOG) signal-transduction pathway.
  • 2009
  • Ingår i: Molecular systems biology. - : EMBO. - 1744-4292. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Cellular signalling networks integrate environmental stimuli with the information on cellular status. These networks must be robust against stochastic fluctuations in stimuli as well as in the amounts of signalling components. Here, we challenge the yeast HOG signal-transduction pathway with systematic perturbations in components' expression levels under various external conditions in search for nodes of fragility. We observe a substantially higher frequency of fragile nodes in this signal-transduction pathway than that has been observed for other cellular processes. These fragilities disperse without any clear pattern over biochemical functions or location in pathway topology and they are largely independent of pathway activation by external stimuli. However, the strongest toxicities are caused by pathway hyperactivation. In silico analysis highlights the impact of model structure on in silico robustness, and suggests complex formation and scaffolding as important contributors to the observed fragility patterns. Thus, in vivo robustness data can be used to discriminate and improve mathematical models.
  •  
16.
  • Krantz, Marcus, 1975, et al. (författare)
  • Robustness and fragility in the yeast High Osmolarity signal transduction pathway
  • 2008
  • Ingår i: 2008 Yeast Genetics and Molecular Biology Meeting Program and Abstract Book, 2008 Yeast Genetics and Molecular Biology Meeting, July 22-27, 2008.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The cellular signalling networks that integrate various environmental stimuli with information on cellular status must be robust to stimuli fluctuations as well as to stochastic differences in the amounts of signalling components. Here, we challenge the Hog signal transduction pathway with systematic disturbances in components’ expression levels implemented by a “genetic tug-of-war”, or gToW, methodology. The disturbances were performed under various external perturbations, including pathway activation by osmotic shock. Ideally, the obtained sensitivity profiles will allow us to impose parameter constraints. However, a more important aspect is the qualitative improvement of model structures, when local fragilities cannot be explained by the model structure. The resulting phenotypes in this particular study reflect a wide range of sensitivities, and disperse without any clear pattern over biochemical functions and pathway modules alike, with the most sensitive nodes being PBS2 and SSK1. Surprisingly, the “neighbouring” nodes HOG1 and SSK2 were affected to a much lesser extent, questioning our current understanding.
  •  
17.
  • Krantz, Marcus, 1975, et al. (författare)
  • Robustness and fragility in the yeast High Osmolarity signal transduction pathway
  • 2008
  • Ingår i: 9th International Conference on Systems Biology (ICSB2008) proceedings, 9th International Conference on Systems Biology (ICSB2008), August 22-28, Gothenburg.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Objective: The cellular signalling networks that integrate various environmental stimuli with information on cellular status must be robust to stimuli fluctuations as well as to stochastic differences in the amounts of signalling components. Here, we challenge the high osmolarity glycerol response (HOG) signal transduction pathway in the yeast Saccharomyces cerevisiae with systematic disturbances in components’ expression levels implemented by a “genetic tug-of-war”, or gTOW, methodology. Results: The disturbances were performed under various external perturbations, including pathway activation by osmotic shock. The resulting phenotypes in this particular study reflect a wide range of sensitivities, and disperse without any clear pattern over biochemical functions and pathway modules alike, with the most sensitive nodes being PBS2 and SSK1. Conclusions: Ideally, the obtained sensitivity profiles will allow us to impose parameter constraints. However, a more important aspect is the qualitative improvement of model structures, when local fragilities cannot be explained by the model structure. Surprisingly, the “neighboring” nodes HOG1 and SSK2 were affected to a much lesser extent, questioning our current understanding.
  •  
18.
  • Ottosson, Lars-Göran, et al. (författare)
  • Robustness analysis of HOG pathway related genes in budding yeast
  • 2007
  • Ingår i: ICSB 2007 Conference Proceedings, 8th International Conference on Systems Biology (ICSB2007), October 1-6, 2007.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • We applied a novel genetic screening method, named “genetic tug-of-war” (gTOW) to estimate the upper limit of gene copy numbers in Saccharomyces cerevisiae. The study involved 29 HOG pathway related genes which included kinases, phosphatases and transcription factors to cover different set of players in the signal transduction system. In addition a phenotypic profiling was conducted in four different growth conditions with three outputs: lag phase, growth phase and efficiency of growth. A number of interesting hits were identified, including PBS2 which had low numbers of gene copies. It will be of interest to expand the study to encompass the entire known signal transduction system in yeast to search for sensitive nodes.
  •  
19.
  • Ottosson, Lars-Göran, et al. (författare)
  • Robustness and fragility in the yeast High Osmolarity Glycerol (HOG) signal transduction pathway
  • 2009
  • Ingår i: Abstracts of the 24th International Conference on Yeast Genetics and Molecular Biology (Supplement to Yeast Volume 26 Issue S1), 25th International Conference on Yeast Genetics & Molecular Biology, July 19-24, Manchester, UK. ; 26:Issue S1
  • Konferensbidrag (refereegranskat)abstract
    • Cellular signalling networks integrate environmental stimuli with information on cellular status. These networks must be robust against stochastic fluctuations in stimuli as well as in the amounts of signalling components. Here, we challenge the yeast HOG signal transduction pathway with systematic perturbations in components’ expression levels implemented by a “genetic tug-of-war” methodology under various external conditions in search of nodes of fragilities. We observe a substantially higher frequency of fragile nodes in this signal transduction pathway than has been observed for other cellular processes. These fragilities disperse without any clear pattern over biochemical functions or location in pathway topology, with the most sensitive node being the scaffold protein PBS2. They are also largely independent of pathway activation by external stimuli. However, the strongest toxicities are caused by pathway hyperactivation. In silico analysis highlights the impact of model structure on in silico robustness, and suggests complex formation and scaffolding as important contributors to the observed fragility patterns. Thus, in vivo robustness data can be used to discriminate and improve mathematical models.
  •  
20.
  • Parts, Leopold, et al. (författare)
  • Revealing the genetic structure of a trait by sequencing a population under selection.
  • 2011
  • Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 21:7, s. 1131-8
  • Tidskriftsartikel (refereegranskat)abstract
    • One approach to understanding the genetic basis of traits is to study their pattern of inheritance among offspring of phenotypically different parents. Previously, such analysis has been limited by low mapping resolution, high labor costs, and large sample size requirements for detecting modest effects. Here, we present a novel approach to map trait loci using artificial selection. First, we generated populations of 10-100 million haploid and diploid segregants by crossing two budding yeast strains of different heat tolerance for up to 12 generations. We then subjected these large segregant pools to heat stress for up to 12 d, enriching for beneficial alleles. Finally, we sequenced total DNA from the pools before and during selection to measure the changes in parental allele frequency. We mapped 21 intervals with significant changes in genetic background in response to selection, which is several times more than found with traditional linkage methods. Nine of these regions contained two or fewer genes, yielding much higher resolution than previous genomic linkage studies. Multiple members of the RAS/cAMP signaling pathway were implicated, along with genes previously not annotated with heat stress response function. Surprisingly, at most selected loci, allele frequencies stopped changing before the end of the selection experiment, but alleles did not become fixed. Furthermore, we were able to detect the same set of trait loci in a population of diploid individuals with similar power and resolution, and observed primarily additive effects, similar to what is seen for complex trait genetics in other diploid organisms such as humans.
  •  
21.
  • Stenberg, Simon, et al. (författare)
  • Control of mitochondrial superoxide production includes programmed mtDNA deletion and restoration
  • 2020
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Deletion of mitochondrial DNA in eukaryotes is mainly attributed to rare accidental events associated with mitochondrial replication or repair of double-strand breaks. We report the discovery that yeast cells arrest harmful intramitochondrial superoxide production by shutting down respiration through genetically controlled deletion of mitochondrial oxidative phosphorylation genes. We show that the regulatory circuitry underlying this editing critically involves the antioxidant enzyme superoxide dismutase 2 and two-way mitochondrial-nuclear communication. While mitochondrial DNA homeostasis is rapidly restored after cessation of a short-term superoxide stress, long-term stress causes maladaptive persistence of the deletion process, leading to complete annihilation of the cellular pool of intact mitochondrial genomes and irrevocable loss of respiratory ability. Our results may therefore be of etiological as well as therapeutic importance with regard to age-related mitochondrial impairment and disease.One-Sentence SummaryGenetically controlled editing of mitochondrial DNA is an integral part of the yeast’s defenses against oxidative damage.
  •  
22.
  • Stenberg, Simon, et al. (författare)
  • Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation
  • 2022
  • Ingår i: eLife. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Deletion of mitochondrial DNA in eukaryotes is currently attributed to rare accidental events associated with mitochondrial replication or repair of double-strand breaks. We report the discovery that yeast cells arrest harmful intramitochondrial superoxide production by shutting down respiration through genetically controlled deletion of mitochondrial oxidative phosphorylation genes. We show that this process critically involves the antioxidant enzyme superoxide dismutase 2 and two-way mitochondrial-nuclear communication through Rtg2 and Rtg3. While mitochondrial DNA homeostasis is rapidly restored after cessation of a short-term superoxide stress, long-term stress causes maladaptive persistence of the deletion process, leading to complete annihilation of the cellular pool of intact mitochondrial genomes and irrevocable loss of respiratory ability. This shows that oxidative stress-induced mitochondrial impairment may be under strict regulatory control. If the results extend to human cells, the results may prove to be of etiological as well as therapeutic importance with regard to age-related mitochondrial impairment and disease.
  •  
23.
  • Warringer, Jonas, 1973, et al. (författare)
  • Trait variation in yeast is defined by population history.
  • 2011
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:6
  • Tidskriftsartikel (refereegranskat)abstract
    • A fundamental goal in biology is to achieve a mechanistic understanding of how and to what extent ecological variation imposes selection for distinct traits and favors the fixation of specific genetic variants. Key to such an understanding is the detailed mapping of the natural genomic and phenomic space and a bridging of the gap that separates these worlds. Here we chart a high-resolution map of natural trait variation in one of the most important genetic model organisms, the budding yeast Saccharomyces cerevisiae, and its closest wild relatives and trace the genetic basis and timing of major phenotype changing events in its recent history. We show that natural trait variation in S. cerevisiae exceeds that of its relatives, despite limited genetic variation, and follows the population history rather than the source environment. In particular, the West African population is phenotypically unique, with an extreme abundance of low-performance alleles, notably a premature translational termination signal in GAL3 that cause inability to utilize galactose. Our observations suggest that many S. cerevisiae traits may be the consequence of genetic drift rather than selection, in line with the assumption that natural yeast lineages are remnants of recent population bottlenecks. Disconcertingly, the universal type strain S288C was found to be highly atypical, highlighting the danger of extrapolating gene-trait connections obtained in mosaic, lab-domesticated lineages to the species as a whole. Overall, this study represents a step towards an in-depth understanding of the causal relationship between co-variation in ecology, selection pressure, natural traits, molecular mechanism, and alleles in a key model organism.
  •  
24.
  • Alalam, Hanna, et al. (författare)
  • Conjugation factors controlling F-plasmid antibiotic resistance transmission
  • 2018
  • Ingår i: BioRxiv. - : Cold Spring Harbor Laboratory.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The rapid horizontal transmission of many antibiotic resistance genes between bacterial host cells on conjugative plasmids is a major cause of the accelerating antibiotic resistance crisis. Preventing understanding and targeting conjugation, there currently are no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation. We introduce a novel experimental framework to screen for conjugation based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. Plasmid-carrying donor strains are constructed in high throughput. We then mix the resistance plasmid carrying donors with recipients in a design where only transconjugants can reproduce, measure growth in dense intervals and extract transmission times as the growth lag. As proof-of-principle, we exhaustively explored chromosomal genes controlling F plasmid donation within E. coli populations, by screening the Keio deletion collection at high replication. We recover all six known chromosomal gene mutants affecting conjugation and identify >50 novel factors, all of which diminish antibiotic resistance transmission. We verify 10 of the novel genes' effects in a liquid mating assay. The new framework holds great potential for exhaustive disclosing of candidate targets for helper drugs that delay resistance development in patients and societies and improves the longevity of current and future antibiotics.
  •  
25.
  • Babazadeh, Roja, et al. (författare)
  • The Ashbya gossypiiEF-1α promoter of the ubiquitously used MX cassettes is toxic to Saccharomyces cerevisiae.
  • 2011
  • Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793.
  • Tidskriftsartikel (refereegranskat)abstract
    • Protein overexpression based on introduction of multiple gene copies is well established. To improve purification or quantification, proteins are typically fused to peptide tags. In Saccharomyces cerevisiae, this has been hampered by multicopy toxicity of the TAP and GFP cassettes used in the global strain collections. Here, we show that this effect is due to the EF-1α promoter in the HIS3MX marker cassette rather than the tags per se. This promoter is frequently used in heterologous marker cassettes, including HIS3MX, KanMX, NatMX, PatMX and HphMX. Toxicity could be eliminated by promoter replacement or exclusion of the marker cassette. To our knowledge, this is the first report of toxicity caused by introduction of a heterologous promoter alone.
  •  
26.
  • Benkwitz-Bedford, Sam, et al. (författare)
  • Machine Learning Prediction of Resistance to Subinhibitory Antimicrobial Concentrations from Escherichia coli Genomes.
  • 2021
  • Ingår i: mSystems. - 2379-5077. ; 6:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Escherichia coli is an important cause of bacterial infections worldwide, with multidrug-resistant strains incurring substantial costs on human lives. Besides therapeutic concentrations of antimicrobials in health care settings, the presence of subinhibitory antimicrobial residues in the environment and in clinics selects for antimicrobial resistance (AMR), but the underlying genetic repertoire is less well understood. Here, we used machine learning to predict the population doubling time and cell growth yield of 1,407 genetically diverse E. coli strains expanding under exposure to three subinhibitory concentrations of six classes of antimicrobials from single-nucleotide genetic variants, accessory gene variation, and the presence of known AMR genes. We predicted cell growth yields in the held-out test data with an average correlation (Spearman's ρ) of 0.63 (0.36 to 0.81 across concentrations) and cell doubling times with an average correlation of 0.59 (0.32 to 0.92 across concentrations), with moderate increases in sample size unlikely to improve predictions further. This finding points to the remaining missing heritability of growth under antimicrobial exposure being explained by effects that are too rare or weak to be captured unless sample size is dramatically increased, or by effects other than those conferred by the presence of individual single-nucleotide polymorphisms (SNPs) and genes. Predictions based on whole-genome information were generally superior to those based only on known AMR genes and were accurate for AMR resistance at therapeutic concentrations. We pinpointed genes and SNPs determining the predicted growth and thereby recapitulated many known AMR determinants. Finally, we estimated the effect sizes of resistance genes across the entire collection of strains, disclosing the growth effects for known resistance genes in each individual strain. Our results underscore the potential of predictive modeling of growth patterns from genomic data under subinhibitory concentrations of antimicrobials, although the remaining missing heritability poses a challenge for achieving the accuracy and precision required for clinical use. IMPORTANCE Predicting bacterial growth from genome sequences is important for a rapid characterization of strains in clinical diagnostics and to disclose candidate novel targets for anti-infective drugs. Previous studies have dissected the relationship between bacterial growth and genotype in mutant libraries for laboratory strains, yet no study so far has examined the predictive power of genome sequence in natural strains. In this study, we used a high-throughput phenotypic assay to measure the growth of a systematic collection of natural Escherichia coli strains and then employed machine learning models to predict bacterial growth from genomic data under nontherapeutic subinhibitory concentrations of antimicrobials that are common in nonclinical settings. We found a moderate to strong correlation between predicted and actual values for the different collected data sets. Moreover, we observed that the known resistance genes are still effective at sublethal concentrations, pointing to clinical implications of these concentrations.
  •  
27.
  • Bergström, Anders, et al. (författare)
  • A high-definition view of functional genetic variation from natural yeast genomes.
  • 2014
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 31:4, s. 872-88
  • Tidskriftsartikel (refereegranskat)abstract
    • The question of how genetic variation in a population influences phenotypic variation and evolution is of major importance in modern biology. Yet much is still unknown about the relative functional importance of different forms of genome variation and how they are shaped by evolutionary processes. Here we address these questions by population level sequencing of 42 strains from the budding yeast Saccharomyces cerevisiae and its closest relative S. paradoxus. We find that genome content variation, in the form of presence or absence as well as copy number of genetic material, is higher within S. cerevisiae than within S. paradoxus, despite genetic distances as measured in single-nucleotide polymorphisms being vastly smaller within the former species. This genome content variation, as well as loss-of-function variation in the form of premature stop codons and frameshifting indels, is heavily enriched in the subtelomeres, strongly reinforcing the relevance of these regions to functional evolution. Genes affected by these likely functional forms of variation are enriched for functions mediating interaction with the external environment (sugar transport and metabolism, flocculation, metal transport, and metabolism). Our results and analyses provide a comprehensive view of genomic diversity in budding yeast and expose surprising and pronounced differences between the variation within S. cerevisiae and that within S. paradoxus. We also believe that the sequence data and de novo assemblies will constitute a useful resource for further evolutionary and population genomics studies.
  •  
28.
  • Brown, William R A, et al. (författare)
  • A Geographically Diverse Collection of Schizosaccharomyces pombe Isolates Shows Limited Phenotypic Variation but Extensive Karyotypic Diversity.
  • 2011
  • Ingår i: G3 (Bethesda, Md.). - : Oxford University Press (OUP). - 2160-1836. ; 1:7, s. 615-26
  • Tidskriftsartikel (refereegranskat)abstract
    • The fission yeast Schizosaccharomyces pombe has been widely used to study eukaryotic cell biology, but almost all of this work has used derivatives of a single strain. We have studied 81 independent natural isolates and 3 designated laboratory strains of Schizosaccharomyces pombe. Schizosaccharomyces pombe varies significantly in size but shows only limited variation in proliferation in different environments compared with Saccharomyces cerevisiae. Nucleotide diversity, π, at a near neutral site, the central core of the centromere of chromosome II is approximately 0.7%. Approximately 20% of the isolates showed karyotypic rearrangements as detected by pulsed field gel electrophoresis and filter hybridization analysis. One translocation, found in 6 different isolates, including the type strain, has a geographically widespread distribution and a unique haplotype and may be a marker of an incipient speciation event. All of the other translocations are unique. Exploitation of this karyotypic diversity may cast new light on both the biology of telomeres and centromeres and on isolating mechanisms in single-celled eukaryotes.
  •  
29.
  • Brown, William R A, et al. (författare)
  • Kinetochore assembly and heterochromatin formation occur autonomously in Schizosaccharomyces pombe.
  • 2014
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 111:5, s. 1903-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Kinetochores in multicellular eukaryotes are usually associated with heterochromatin. Whether this heterochromatin simply promotes the cohesion necessary for accurate chromosome segregation at cell division or whether it also has a role in kinetochore assembly is unclear. Schizosaccharomyces pombe is an important experimental system for investigating centromere function, but all of the previous work with this species has exploited a single strain or its derivatives. The laboratory strain and most other S. pombe strains contain three chromosomes, but one recently discovered strain, CBS 2777, contains four. We show that the genome of CBS 2777 is related to that of the laboratory strain by a complex chromosome rearrangement. As a result, two of the kinetochores in CBS 2777 contain the central core sequences present in the laboratory strain centromeres, but lack adjacent heterochromatin. The closest block of heterochromatin to these rearranged kinetochores is ∼100 kb away at new telomeres. Despite lacking large amounts of adjacent heterochromatin, the rearranged kinetochores bind CENP-A(Cnp1) and CENP-C(Cnp3) in similar quantities and with similar specificities as those of the laboratory strain. The simplest interpretation of this result is that constitutive kinetochore assembly and heterochromatin formation occur autonomously.
  •  
30.
  • Cubillos, Francisco A, et al. (författare)
  • Assessing the complex architecture of polygenic traits in diverged yeast populations.
  • 2011
  • Ingår i: Molecular ecology. - 1365-294X. ; 20:7, s. 1401-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Phenotypic variation arising from populations adapting to different niches has a complex underlying genetic architecture. A major challenge in modern biology is to identify the causative variants driving phenotypic variation. Recently, the baker's yeast, Saccharomyces cerevisiae has emerged as a powerful model for dissecting complex traits. However, past studies using a laboratory strain were unable to reveal the complete architecture of polygenic traits. Here, we present a linkage study using 576 recombinant strains obtained from crosses of isolates representative of the major lineages. The meiotic recombinational landscape appears largely conserved between populations; however, strain-specific hotspots were also detected. Quantitative measurements of growth in 23 distinct ecologically relevant environments show that our recombinant population recapitulates most of the standing phenotypic variation described in the species. Linkage analysis detected an average of 6.3 distinct QTLs for each condition tested in all crosses, explaining on average 39% of the phenotypic variation. The QTLs detected are not constrained to a small number of loci, and the majority are specific to a single cross-combination and to a specific environment. Moreover, crosses between strains of similar phenotypes generate greater variation in the offspring, suggesting the presence of many antagonistic alleles and epistatic interactions. We found that subtelomeric regions play a key role in defining individual quantitative variation, emphasizing the importance of the adaptive nature of these regions in natural populations. This set of recombinant strains is a powerful tool for investigating the complex architecture of polygenic traits.
  •  
31.
  • Cubillos, Francisco A, et al. (författare)
  • High-resolution mapping of complex traits with a four-parent advanced intercross yeast population.
  • 2013
  • Ingår i: Genetics. - : Oxford University Press (OUP). - 1943-2631. ; 195:3, s. 1141-55
  • Tidskriftsartikel (refereegranskat)abstract
    • A large fraction of human complex trait heritability is due to a high number of variants with small marginal effects and their interactions with genotype and environment. Such alleles are more easily studied in model organisms, where environment, genetic makeup, and allele frequencies can be controlled. Here, we examine the effect of natural genetic variation on heritable traits in a very large pool of baker's yeast from a multiparent 12th generation intercross. We selected four representative founder strains to produce the Saccharomyces Genome Resequencing Project (SGRP)-4X mapping population and sequenced 192 segregants to generate an accurate genetic map. Using these individuals, we mapped 25 loci linked to growth traits under heat stress, arsenite, and paraquat, the majority of which were best explained by a diverging phenotype caused by a single allele in one condition. By sequencing pooled DNA from millions of segregants grown under heat stress, we further identified 34 and 39 regions selected in haploid and diploid pools, respectively, with most of the selection against a single allele. While the most parsimonious model for the majority of loci mapped using either approach was the effect of an allele private to one founder, we could validate examples of pleiotropic effects and complex allelic series at a locus. SGRP-4X is a deeply characterized resource that provides a framework for powerful and high-resolution genetic analysis of yeast phenotypes and serves as a test bed for testing avenues to attack human complex traits.
  •  
32.
  • D'Angiolo, M., et al. (författare)
  • A yeast living ancestor reveals the origin of genomic introgressions
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587, s. 420-425
  • Tidskriftsartikel (refereegranskat)abstract
    • A yeast clonal descendant of an ancient hybridization event is identified and sheds light on the early evolution of the Saccharomyces cerevisiae Alpechin lineage and its abundant Saccharomyces paradoxus introgressions. Genome introgressions drive evolution across the animal(1), plant(2) and fungal(3) kingdoms. Introgressions initiate from archaic admixtures followed by repeated backcrossing to one parental species. However, how introgressions arise in reproductively isolated species, such as yeast(4), has remained unclear. Here we identify a clonal descendant of the ancestral yeast hybrid that founded the extant Saccharomyces cerevisiae Alpechin lineage(5), which carries abundant Saccharomyces paradoxus introgressions. We show that this clonal descendant, hereafter defined as a 'living ancestor', retained the ancestral genome structure of the first-generation hybrid with contiguous S. cerevisiae and S. paradoxus subgenomes. The ancestral first-generation hybrid underwent catastrophic genomic instability through more than a hundred mitotic recombination events, mainly manifesting as homozygous genome blocks generated by loss of heterozygosity. These homozygous sequence blocks rescue hybrid fertility by restoring meiotic recombination and are the direct origins of the introgressions present in the Alpechin lineage. We suggest a plausible route for introgression evolution through the reconstruction of extinct stages and propose that genome instability allows hybrids to overcome reproductive isolation and enables introgressions to emerge.
  •  
33.
  • De Chiara, Matteo, et al. (författare)
  • Domestication reprogrammed the budding yeast life cycle
  • 2022
  • Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X .- 2397-334X. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Domestication of plants and animals is the foundation for feeding the world human population but can profoundly alter the biology of the domesticated species. Here we investigated the effect of domestication on one of our prime model organisms, the yeast Saccharomyces cerevisiae, at a species-wide level. We tracked the capacity for sexual and asexual reproduction and the chronological life span across a global collection of 1,011 genome-sequenced yeast isolates and found a remarkable dichotomy between domesticated and wild strains. Domestication had systematically enhanced fermentative and reduced respiratory asexual growth, altered the tolerance to many stresses and abolished or impaired the sexual life cycle. The chronological life span remained largely unaffected by domestication and was instead dictated by clade-specific evolution. We traced the genetic origins of the yeast domestication syndrome using genome-wide association analysis and genetic engineering and disclosed causative effects of aneuploidy, gene presence/absence variations, copy number variations and single-nucleotide polymorphisms. Overall, we propose domestication to be the most dramatic event in budding yeast evolution, raising questions about how much domestication has distorted our understanding of the natural biology of this key model species.
  •  
34.
  • Esguerra, Jonathan, 1976, et al. (författare)
  • Functional importance of individual rRNA 2'-O-ribose methylations revealed by high-resolution phenotyping
  • 2008
  • Ingår i: RNA. - 1469-9001. ; 14:4, s. 649-56
  • Tidskriftsartikel (refereegranskat)abstract
    • Ribosomal RNAs contain numerous modifications at specific nucleotides. Despite their evolutionary conservation, the functional role of individual 2'-O-ribose methylations in rRNA is not known. A distinct family of small nucleolar RNAs, box C/D snoRNAs, guides the methylating complex to specific rRNA sites. Using a high-resolution phenotyping approach, we characterized 20 box C/D snoRNA gene deletions for altered growth dynamics under a wide array of environmental perturbations, encompassing intraribosomal antibiotics, inhibitors of specific cellular features, as well as general stressors. Ribosome-specific antibiotics generated phenotypes indicating different and long-ranging structural effects of rRNA methylations on the ribosome. For all studied box C/D snoRNA mutants we uncovered phenotypes to extraribosomal growth inhibitors, most frequently reflected in alteration in growth lag (adaptation time). A number of strains were highly pleiotropic and displayed a great number of sensitive phenotypes, e.g., deletion mutants of snR70 and snR71, which both have clear human homologues, and deletion mutants of snR65 and snR68. Our data indicate that individual rRNA ribose methylations can play either distinct or general roles in the workings of the ribosome.
  •  
35.
  • Fernandez-Ricaud, Luciano, 1975, et al. (författare)
  • PRECOG: a tool for automated extraction and visualization of fitness components in microbial growth phenomics
  • 2016
  • Ingår i: Bmc Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Phenomics is a field in functional genomics that records variation in organismal phenotypes in the genetic, epigenetic or environmental context at a massive scale. For microbes, the key phenotype is the growth in population size because it contains information that is directly linked to fitness. Due to technical innovations and extensive automation our capacity to record complex and dynamic microbial growth data is rapidly outpacing our capacity to dissect and visualize this data and extract the fitness components it contains, hampering progress in all fields of microbiology. Results: To automate visualization, analysis and exploration of complex and highly resolved microbial growth data as well as standardized extraction of the fitness components it contains, we developed the software PRECOG (PREsentation and Characterization Of Growth-data). PRECOG allows the user to quality control, interact with and evaluate microbial growth data with ease, speed and accuracy, also in cases of non-standard growth dynamics. Quality indices filter high-from low-quality growth experiments, reducing false positives. The pre-processing filters in PRECOG are computationally inexpensive and yet functionally comparable to more complex neural network procedures. We provide examples where data calibration, project design and feature extraction methodologies have a clear impact on the estimated growth traits, emphasising the need for proper standardization in data analysis. Conclusions: PRECOG is a tool that streamlines growth data pre-processing, phenotypic trait extraction, visualization, distribution and the creation of vast and informative phenomics databases.
  •  
36.
  • Gamfeldt, Lars, 1975, et al. (författare)
  • Scaling-up the biodiversity-ecosystem functioning relationship: the effect of environmental heterogeneity on transgressive overyielding
  • 2023
  • Ingår i: Oikos. - : Wiley. - 0030-1299 .- 1600-0706. ; 2023:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Knowledge of how biodiversity sustains ecosystem function comes predominantly from studies focused on small spatial scales. Thus, we know relatively little about the role of biodiversity at larger scales of space and time where habitats become increasingly heterogeneous. Efforts to upscale the relationship between biodiversity and function have yielded inconclusive results. Given that increasing habitat heterogeneity is a ubiquitous consequence of increasing spatial scale, we asked: as habitat heterogeneity increases, can single species continue to maintain ecosystem function? Or, does transgressive overyielding (functioning of species mixture divided by the functioning of the highest functioning single species) change with habitat heterogeneity? We addressed this using a combination of computer simulations, an experiment and a meta-analysis. The three parts followed the same rationale: habitat heterogeneity was increased by aggregating local habitats with different conditions into larger and more heterogeneous landscapes. The computer simulations showed that, on average, transgressive overyielding increased with habitat heterogeneity because monoculture functioning decreased with habitat heterogeneity. We tested this expectation experimentally by varying the strain richness from one to five species across 10800 bacterial communities in five different habitats defined by sub-inhibitory concentrations of antibiotics. On average, the experimental results concurred with the simulations. We tested the generality of this result using a meta-analysis of 26 published experiments that manipulated habitat conditions and species richness. This confirmed that transgressive overyielding tended to increase with habitat heterogeneity but only when species were specialised to different habitats and were not inhibited in mixtures by negative species interactions. This was not the case in several experiments used in our meta-analysis where one species maximised functioning across all habitats, contrary to the assumptions of many ecological models. Our results illustrate the importance of biodiversity at larger spatial scales with more heterogeneity but also highlights contingencies that this pattern depends on.
  •  
37.
  • García-Martínez, José, et al. (författare)
  • The cellular growth rate controls overall mRNA turnover, and modulates either transcription or degradation rates of particular gene regulons.
  • 2016
  • Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 44:8, s. 3643-3658
  • Tidskriftsartikel (refereegranskat)abstract
    • We analyzed 80 different genomic experiments, and found a positive correlation between both RNA polymerase II transcription and mRNA degradation with growth rates in yeast. Thus, in spite of the marked variation in mRNA turnover, the total mRNA concentration remained approximately constant. Some genes, however, regulated their mRNA concentration by uncoupling mRNA stability from the transcription rate. Ribosome-related genes modulated their transcription rates to increase mRNA levels under fast growth. In contrast, mitochondria-related and stress-induced genes lowered mRNA levels by reducing mRNA stability or the transcription rate, respectively. We also detected these regulations within the heterogeneity of a wild-type cell population growing in optimal conditions. The transcriptomic analysis of sorted microcolonies confirmed that the growth rate dictates alternative expression programs by modulating transcription and mRNA decay.The regulation of overall mRNA turnover keeps a constant ratio between mRNA decay and the dilution of [mRNA] caused by cellular growth. This regulation minimizes the indiscriminate transmission of mRNAs from mother to daughter cells, and favors the response capacity of the latter to physiological signals and environmental changes. We also conclude that, by uncoupling mRNA synthesis from decay, cells control the mRNA abundance of those gene regulons that characterize fast and slow growth.
  •  
38.
  • Gjuvsland, Arne B, et al. (författare)
  • Disentangling genetic and epigenetic determinants of ultrafast adaptation.
  • 2016
  • Ingår i: Molecular systems biology. - : EMBO. - 1744-4292. ; 12:12
  • Tidskriftsartikel (refereegranskat)abstract
    • A major rationale for the advocacy of epigenetically mediated adaptive responses is that they facilitate faster adaptation to environmental challenges. This motivated us to develop a theoretical-experimental framework for disclosing the presence of such adaptation-speeding mechanisms in an experimental evolution setting circumventing the need for pursuing costly mutation-accumulation experiments. To this end, we exposed clonal populations of budding yeast to a whole range of stressors. By growth phenotyping, we found that almost complete adaptation to arsenic emerged after a few mitotic cell divisions without involving any phenotypic plasticity. Causative mutations were identified by deep sequencing of the arsenic-adapted populations and reconstructed for validation. Mutation effects on growth phenotypes, and the associated mutational target sizes were quantified and embedded in data-driven individual-based evolutionary population models. We found that the experimentally observed homogeneity of adaptation speed and heterogeneity of molecular solutions could only be accounted for if the mutation rate had been near estimates of the basal mutation rate. The ultrafast adaptation could be fully explained by extensive positive pleiotropy such that all beneficial mutations dramatically enhanced multiple fitness components in concert. As our approach can be exploited across a range of model organisms exposed to a variety of environmental challenges, it may be used for determining the importance of epigenetic adaptation-speeding mechanisms in general.
  •  
39.
  •  
40.
  •  
41.
  • Graf, Fabrice, et al. (författare)
  • Inhibiting conjugation as a tool in the fight against antibiotic resistance
  • 2019
  • Ingår i: Drug Development Research. - : Wiley. - 0272-4391 .- 1098-2299. ; 80:1, s. 19-23
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2018 Wiley Periodicals, Inc. (Table presented.). Antibiotic resistance, especially in gram-negative bacteria, is spreading globally and rapidly. Development of new antibiotics lags behind; therefore, novel approaches to the problem of antibiotic resistance are sorely needed and this commentary highlights one relatively unexplored target for drug development: conjugation. Conjugation is a common mechanism of horizontal gene transfer in bacteria that is instrumental in the spread of antibiotic resistance among bacteria. Most resistance genes are found on mobile genetic elements and primarily spread by conjugation. Furthermore, conjugative elements can act as a reservoir to maintain antibiotic resistance in the bacterial population even in the absence of antibiotic selection. Thus, conjugation can spread antibiotic resistance quickly between bacteria of the microbiome and pathogens when selective pressure (antibiotics) is introduced. Potential drug targets include the plasmid-encoded conjugation system and the host-encoded proteins important for conjugation. Ideally, a conjugation inhibitor will be used alongside antibiotics to prevent the spread of resistance to or within pathogens while not acting as a growth inhibitor itself. Inhibiting conjugation will be an important addition to our arsenal of strategies to combat the antibiotic resistance crisis, allowing us to extend the usefulness of antibiotics.
  •  
42.
  • Gutierrez, A., et al. (författare)
  • Genetic Basis of Variations in Nitrogen Source Utilization in Four Wine Commercial Yeast Strains
  • 2013
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The capacity of wine yeast to utilize the nitrogen available in grape must directly correlates with the fermentation and growth rates of all wine yeast fermentation stages and is, thus, of critical importance for wine production. Here we precisely quantified the ability of low complexity nitrogen compounds to support fast, efficient and rapidly initiated growth of four commercially important wine strains. Nitrogen substrate abundance in grape must failed to correlate with the rate or the efficiency of nitrogen source utilization, but well predicted lag phase length. Thus, human domestication of yeast for grape must growth has had, at the most, a marginal impact on wine yeast growth rates and efficiencies, but may have left a surprising imprint on the time required to adjust metabolism from non growth to growth. Wine yeast nitrogen source utilization deviated from that of the lab strain experimentation, but also varied between wine strains. Each wine yeast lineage harbored nitrogen source utilization defects that were private to that strain. By a massive hemizygote analysis, we traced the genetic basis of the most glaring of these defects, near inability of the PDM wine strain to utilize methionine, as consequence of mutations in its ARO8, ADE5,7 and VBA3 alleles. We also identified candidate causative mutations in these genes. The methionine defect of PDM is potentially very interesting as the strain can, in some circumstances, overproduce foul tasting H2S, a trait which likely stems from insufficient methionine catabolization. The poor adaptation of wine yeast to the grape must nitrogen environment, and the presence of defects in each lineage, open up wine strain optimization through biotechnological endeavors.
  •  
43.
  • Gutiérrez, Alicia, et al. (författare)
  • Replenishment and mobilization of intracellular nitrogen pools decouples wine yeast nitrogen uptake from growth.
  • 2016
  • Ingår i: Applied microbiology and biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 100:7, s. 3255-65
  • Tidskriftsartikel (refereegranskat)abstract
    • Wine yeast capacity to take up nitrogen from the environment and catabolize it to support population growth, fermentation, and aroma production is critical to wine production. Under nitrogen restriction, yeast nitrogen uptake is believed to be intimately coupled to reproduction with nitrogen catabolite repression (NCR) suggested mediating this link. We provide a time- and strain-resolved view of nitrogen uptake, population growth, and NCR activity in wine yeasts. Nitrogen uptake was found to be decoupled from growth due to early assimilated nitrogen being used to replenish intracellular nitrogen pools rather than being channeled directly into reproduction. Internally accumulated nitrogen was later mobilized to support substantial population expansion after external nitrogen was depleted. On good nitrogen sources, the decoupling between nitrogen uptake and growth correlated well with relaxation of NCR repression, raising the potential that the latter may be triggered by intracellular build-up of nitrogen. No link between NCR activity and nitrogen assimilation or growth on poor nitrogen sources was found. The decoupling between nitrogen uptake and growth and its influence on NCR activity is of relevance for both wine production and our general understanding of nitrogen use.
  •  
44.
  • Hallin, J., et al. (författare)
  • Powerful decomposition of complex traits in a diploid model
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Explaining trait differences between individuals is a core and challenging aim of life sciences. Here, we introduce a powerful framework for complete decomposition of trait variation into its underlying genetic causes in diploid model organisms. We sequence and systematically pair the recombinant gametes of two intercrossed natural genomes into an array of diploid hybrids with fully assembled and phased genomes, termed Phased Outbred Lines (POLs). We demonstrate the capacity of this approach by partitioning fitness traits of 6,642 Saccharomyces cerevisiae POLs across many environments, achieving near complete trait heritability and precisely estimating additive (73%), dominance (10%), second (7%) and third (1.7%) order epistasis components. We map quantitative trait loci (QTLs) and find nonadditive QTLs to outnumber (3:1) additive loci, dominant contributions to heterosis to outnumber overdominant, and extensive pleiotropy. The POL framework offers the most complete decomposition of diploid traits to date and can be adapted to most model organisms.
  •  
45.
  • Herzog, M., et al. (författare)
  • Mutagenic mechanisms of cancer-associated DNA polymerase epsilon alleles
  • 2021
  • Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 49:7, s. 3919-3931
  • Tidskriftsartikel (refereegranskat)abstract
    • A single amino acid residue change in the exonuclease domain of human DNA polymerase epsilon, P286R, is associated with the development of colorectal cancers, and has been shown to impart a mutator phenotype. The corresponding Pol epsilon allele in the yeast Saccharomyces cerevisiae (pol2-P301R), was found to drive greater mutagenesis than an entirely exonuclease-deficient Pol epsilon (pol2-4), an unexpected phenotype of ultra-mutagenesis. By studying the impact on mutation frequency, type, replication-strand bias, and sequence context, we show that ultra-mutagenesis is commonly observed in yeast cells carrying a range of cancer-associated Pol epsilon exonuclease domain alleles. Similarities between mutations generated by these alleles and those generated in pol2-4 cells indicate a shared mechanism of mutagenesis that yields a mutation pattern similar to cancer Signature 14. Comparison of POL2 ultra-mutator with pol2-M644G, amutant in the polymerase domain decreasing Pol epsilon fidelity, revealed unexpected analogies in the sequence context and strand bias of mutations. Analysis of mutational patterns unique to exonuclease domain mutant cells suggests that backtracking of the polymerase, when the mismatched primer end cannot be accommodated in the proofreading domain, results in the observed insertions and T>A mutations in specific sequence contexts.
  •  
46.
  • Hodgins-Davis, Andrea, et al. (författare)
  • Abundant Gene-by-Environment Interactions in Gene Expression Reaction Norms to Copper within Saccharomyces cerevisiae.
  • 2012
  • Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 4:11, s. 1061-79
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variation for plastic phenotypes potentially contributes phenotypic variation to populations that can be selected during adaptation to novel ecological contexts. However, the basis and extent of plastic variation that manifests in diverse environments remains elusive. Here, we characterize copper reaction norms for mRNA abundance among five Saccharomyces cerevisiae strains to 1) describe population variation across the full range of ecologically relevant copper concentrations, from starvation to toxicity, and 2) to test the hypothesis that plastic networks exhibit increased population variation for gene expression. We find that although the vast majority of the variation is small in magnitude (considerably <2-fold), not just some, but most genes demonstrate variable expression across environments, across genetic backgrounds, or both. Plastically expressed genes included both genes regulated directly by copper-binding transcription factors Mac1 and Ace1 and genes indirectly responding to the downstream metabolic consequences of the copper gradient, particularly genes involved in copper, iron, and sulfur homeostasis. Copper-regulated gene networks exhibited more similar behavior within the population in environments where those networks have a large impact on fitness. Nevertheless, expression variation in genes like Cup1, important to surviving copper stress, was linked with variation in mitotic fitness and in the breadth of differential expression across the genome. By revealing a broader and deeper range of population variation, our results provide further evidence for the interconnectedness of genome-wide mRNA levels, their dependence on environmental context and genetic background, and the abundance of variation in gene expression that can contribute to future evolution.
  •  
47.
  • Ibstedt, Sebastian, 1983, et al. (författare)
  • Concerted Evolution of Life Stage Performances Signals Recent Selection on Yeast Nitrogen Use.
  • 2015
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 32:1, s. 153-161
  • Tidskriftsartikel (refereegranskat)abstract
    • Exposing natural selection driving phenotypic and genotypic adaptive differentiation is an extraordinary challenge. Given that an organism's life stages are exposed to the same environmental variations, we reasoned that fitness components, such as the lag, rate, and efficiency of growth, directly reflecting performance in these life stages, should often be selected in concert. We therefore conjectured that correlations between fitness components over natural isolates, in a particular environmental context, would constitute a robust signal of recent selection. Critically, this test for selection requires fitness components to be determined by different genetic loci. To explore our conjecture, we exhaustively evaluated the lag, rate, and efficiency of asexual population growth of natural isolates of the model yeast Saccharomyces cerevisiae in a large variety of nitrogen-limited environments. Overall, fitness components were well correlated under nitrogen restriction. Yeast isolates were further crossed in all pairwise combinations and coinheritance of each fitness component and genetic markers were traced. Trait variations tended to map to quantitative trait loci (QTL) that were private to a single fitness component. We further traced QTLs down to single-nucleotide resolution and uncovered loss-of-function mutations in RIM15, PUT4, DAL1, and DAL4 as the genetic basis for nitrogen source use variations. Effects of SNPs were unique for a single fitness component, strongly arguing against pleiotropy between lag, rate, and efficiency of reproduction under nitrogen restriction. The strong correlations between life stage performances that cannot be explained by pleiotropy compellingly support adaptive differentiation of yeast nitrogen source use and suggest a generic approach for detecting selection.
  •  
48.
  • Ibstedt, Sebastian, 1983, et al. (författare)
  • Dissection of advanced intercross lines provides information on evolution of yeast in shifting metal abundances
  • 2012
  • Ingår i: Experimental Approaches to Evolution and Ecology using Yeast (EMBO, Heidelberg, October 2012). ; 2012
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Metals can be friends or foes, depending on their chemical reactivity, dose or mode of exposure. Unfortunately, a general perspective on the importance of different processes for maintaining evolutionary flexibility and physiological homeostasis with regard to metal exposure is lacking. In order to understand the processes that contribute to metal toxicity and resistance in natural populations of Saccharomyces cerevisiae, we have analyzed a twelfth generation intercross between geographically and ecologically distinct populations. Large-scale phenotyping of highly recombined segregants allows us to pinpoint causative alleles to narrow intervals and to make inferences about the evolutionary history of complex traits in natural populations with regard to pleiotropy and epistasis. We show that metal detoxification in Saccharomyces cerevisiae is highly dependent on specific stress, while epistasis depends on population-specific alleles. These results are consistent with an evolutionary history of bottle-necks, rapid dispersion into ecologically differing habitats followed by independent evolutionary paths.
  •  
49.
  • Jansson, Kristina, 1969, et al. (författare)
  • The tumor suppressor homolog in fission yeast, myh1+, displays a strong interaction with the checkpoint gene rad1
  • 2008
  • Ingår i: Mutation Research. - : Elsevier BV. ; 644, s. 48-55
  • Tidskriftsartikel (refereegranskat)abstract
    • The DNA glycosylase MutY is strongly conserved in evolution, and homologs are found in most eukaryotes and prokaryotes examined. This protein is implicated in repair of oxidative DNA damage, in particular adenine mispaired opposite 7,8-dihydro-8-oxoguanine. Previous investigations in Escherichia coli, fission yeast, and mammalian cells show an association of mutations in MutY homologs with a mutator phenotype and carcinogenesis. Eukaryotic MutY homologs physically associate with several proteins with a role in replication, DNA repair, and checkpoint signaling, specifically the trimeric 9-1-1 complex. In a genetic investigation of the fission yeast MutY homolog, myh1+, we show that the myh1 mutation confers a moderately increased UV sensitivity alone and in combination with mutations in several DNA repair genes. The myh1 rad1, and to a lesser degree myh1 rad9, double mutants display a synthetic interaction resulting in enhanced sensitivity to DNA damaging agents and hydroxyurea. UV irradiation of myh1 rad1 double mutants results in severe chromosome segregation defects and visible DNA fragmentation, and a failure to activate the checkpoint. Additionally, myh1 rad1 double mutants exhibit morphological defects in the absence of DNA damaging agents.We also found a moderate suppression of the slow growth and UV sensitivity of rhp51 mutants by the myh1 mutation. Our results implicate fission yeast Myh1 in repair of a wider range of DNA damage than previously thought, and functionally link it to the checkpoint pathway.
  •  
50.
  • Jouhten, P., et al. (författare)
  • Predictive evolution of metabolic phenotypes using model-designed environments
  • 2022
  • Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 18:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Adaptive evolution under controlled laboratory conditions has been highly effective in selecting organisms with beneficial phenotypes such as stress tolerance. The evolution route is particularly attractive when the organisms are either difficult to engineer or the genetic basis of the phenotype is complex. However, many desired traits, like metabolite secretion, have been inaccessible to adaptive selection due to their trade-off with cell growth. Here, we utilize genome-scale metabolic models to design nutrient environments for selecting lineages with enhanced metabolite secretion. To overcome the growth-secretion trade-off, we identify environments wherein growth becomes correlated with a secondary trait termed tacking trait. The latter is selected to be coupled with the desired trait in the application environment where the trait manifestation is required. Thus, adaptive evolution in the model-designed selection environment and subsequent return to the application environment is predicted to enhance the desired trait. We experimentally validate this strategy by evolving Saccharomyces cerevisiae for increased secretion of aroma compounds, and confirm the predicted flux-rerouting using genomic, transcriptomic, and proteomic analyses. Overall, model-designed selection environments open new opportunities for predictive evolution.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-50 av 92
Typ av publikation
tidskriftsartikel (79)
konferensbidrag (11)
bokkapitel (2)
Typ av innehåll
refereegranskat (79)
övrigt vetenskapligt/konstnärligt (13)
Författare/redaktör
Warringer, Jonas, 19 ... (91)
Blomberg, Anders, 19 ... (40)
Liti, Gianni (22)
Stenberg, Simon (13)
Farewell, Anne, 1961 (12)
Zackrisson, Martin (12)
visa fler...
Liti, G. (12)
Sunnerhagen, Per, 19 ... (11)
Persson, Karl, 1988 (11)
Ottosson, Lars-Göran (10)
Krantz, Marcus, 1975 (9)
Hohmann, Stefan, 195 ... (9)
Palm, Martin (9)
Parts, Leopold (9)
Louis, Edward J (9)
Ahmadpour, Doryaneh, ... (8)
Ghiaci, Payam (7)
Cubillos, Francisco ... (7)
Graf, Fabrice (6)
Molin, Mikael, 1973 (6)
Mustonen, Ville (6)
Durbin, Richard (6)
Yue, Jia Xing (6)
Salinas, Francisco (6)
Nerman, Olle, 1951 (5)
Hallin, Johan (5)
Zörgö, Enikö, 1968 (5)
Fernandez-Ricaud, Lu ... (5)
Li, Jing (4)
Bergström, Anders (4)
Alalam, Hanna (4)
Barré, Benjamin P. (4)
Zia, Amin (4)
Snipen, Lars (4)
Omholt, Stig (4)
Ibstedt, Sebastian, ... (4)
Yue, J. X. (4)
Li, J. (3)
Käll, Mikael, 1963 (3)
Tamás, Markus J., 19 ... (3)
Gilchrist, Ciaran (3)
Simpson, Jared T. (3)
Irizar, Agurtzane (3)
Moses, Alan M (3)
Logg, Katarina, 1979 (3)
Klipp, Edda (3)
De Chiara, M. (3)
De Chiara, Matteo (3)
Larsson Berglund, Li ... (3)
Ericson, Elke, 1973 (3)
visa färre...
Lärosäte
Göteborgs universitet (89)
Chalmers tekniska högskola (29)
Stockholms universitet (1)
Jönköping University (1)
Lunds universitet (1)
RISE (1)
visa fler...
Karolinska Institutet (1)
visa färre...
Språk
Engelska (92)
Forskningsämne (UKÄ/SCB)
Naturvetenskap (90)
Medicin och hälsovetenskap (17)
Teknik (1)
Lantbruksvetenskap (1)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy