APC Microbiome Ireland - Journal Articles

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    Development of a ribosome profiling protocol to study translation in Kluyveromyces marxianus
    (Oxford University Press, 2022) Fenton, Darren; Kiniry, Stephen J.; Yordanova, Martina M.; Baranov, Pavel V.; Morrissey, John P.; Horizon 2020 Framework Programme; Science Foundation Ireland; Health Research Board; Wellcome Trust
    Kluyveromyces marxianus is an interesting and important yeast because of particular traits such as thermotolerance and rapid growth, and for applications in food and industrial biotechnology. For both understanding its biology and developing bioprocesses, it is important to understand how K. marxianus responds and adapts to changing environments. For this, a full suite of omics tools to measure and compare global patterns of gene expression and protein synthesis is needed. We report here the development of a ribosome profiling method for K. marxianus, which allows codon resolution of translation on a genome-wide scale by deep sequencing of ribosome locations on mRNAs. To aid in the analysis and sharing of ribosome profiling data, we added the K. marxianus genome as well as transcriptome and ribosome profiling data to the publicly accessible GWIPS-viz and Trips-Viz browsers. Users are able to upload custom ribosome profiling and RNA-Seq data to both browsers, therefore allowing easy analysis and sharing of data. We also provide a set of step-by-step protocols for the experimental and bioinformatic methods that we developed.
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    Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0
    (Springer Nature, 2022) Domenzain, Ivan; Sánchez, Benjamín; Anton, Mihail; Kerkhoven, Eduard J.; Millan-Oropeza, Aaron; Henry, Celine; Siewers, Verena; Morrissey, John P.; Sonnenschein, Nikolaus; Nielsen, Jens; Horizon 2020 Framework Programme; Knut och Alice Wallenbergs Stiftelse; Novo Nordisk Fonden
    Genome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration of enzyme constraints and proteomics data into such models was first enabled by the GECKO toolbox, allowing the study of phenotypes constrained by protein limitations. Here, we upgrade the toolbox in order to enhance models with enzyme and proteomics constraints for any organism with a compatible GEM reconstruction. With this, enzyme-constrained models for the budding yeasts Saccharomyces cerevisiae, Yarrowia lipolytica and Kluyveromyces marxianus are generated to study their long-term adaptation to several stress factors by incorporation of proteomics data. Predictions reveal that upregulation and high saturation of enzymes in amino acid metabolism are common across organisms and conditions, suggesting the relevance of metabolic robustness in contrast to optimal protein utilization as a cellular objective for microbial growth under stress and nutrient-limited conditions. The functionality of GECKO is expanded with an automated framework for continuous and version-controlled update of enzyme-constrained GEMs, also producing such models for Escherichia coli and Homo sapiens. In this work, we facilitate the utilization of enzyme-constrained GEMs in basic science, metabolic engineering and synthetic biology purposes.
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    Gut microbiota and eating behaviour in circadian syndrome
    (Elsevier Ltd., 2024-08-01) Soliz-Rueda, Jorge R.; Cuesta-Marti, Cristina; O’Mahony, Siobhain M.; Clarke, Gerard; Schellekens, Harriët; Muguerza, Begoña; Science Foundation Ireland; Ministerio de Ciencia e Innovación; Irish Research Council; Ministerio de Universidades; Biostime Institute for Nutrition and Care – Geneva; Food for Health Ireland
    Eating behaviour and circadian rhythms are closely related. The type, timing, and quantity of food consumed, and host circadian rhythms, directly influence the intestinal microbiota, which in turn impacts host circadian rhythms and regulates food intake beyond homeostatic eating. This Opinion discusses the impact of food intake and circadian disruptions induced by an obesogenic environment on gut–brain axis signalling. We also explore potential mechanisms underlying the effects of altered gut microbiota on food intake behaviour and circadian rhythmicity. Understanding the crosstalk between gut microbiota, circadian rhythms, and unhealthy eating behaviour is crucial to addressing the obesity epidemic, which remains one of the biggest societal challenges of our time.
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    Genetic epidemiology of eating disorders
    (Wolters Kluwer Health, Inc., 2016-11) Bulik, Cynthia M.; Kleiman, Susan C.; Yilmaz, Zeynep; Vetenskapsrådet; Klarman Family Foundation; National Institutes of Health
    Purpose of review: We capture recent findings in the field of genetic epidemiology of eating disorders. As analytic techniques evolve for twin, population, and molecular genetic studies, new findings emerge at an accelerated pace. We present the current status of knowledge regarding the role of genetic and environmental factors that influence risk for eating disorders. Recent findings: We focus on novel findings from twin studies, population studies using genetically informative designs, and molecular genetic studies. Over the past 2 years, research in this area has yielded insights into: comorbidity with other psychiatric and medical disorders and with metabolic traits; developmental factors associated with the emergence of eating disorders; and the molecular genetics of anorexia nervosa. Summary: Insights from genetic epidemiology provide an important explanatory model for patients with eating disorders, family members, and clinicians. Understanding core biological determinants that explain the severity and persistence of the illnesses, their frequent co-occurrence with other conditions, and their familial patterns raises awareness and increases compassion for individuals living with these disorders. Large-scale genomic studies are currently underway. Ultimately, this domain of research may pave the way to greater understanding of the underlying neurobiology and inform the development of novel and effective interventions.
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    Bacteriocin diversity, function, discovery and application as antimicrobials
    (Springer Nature, 2024-05-10) Sugrue, Ivan; Ross, R. Paul; Hill, Colin
    Bacteriocins are potent antimicrobial peptides that are produced by bacteria. Since their discovery almost a century ago, diverse peptides have been discovered and described, and some are currently used as commercial food preservatives. Many bacteriocins exhibit extensively post-translationally modified structures encoded on complex gene clusters, whereas others have simple linear structures. The molecular structures, mechanisms of action and resistance have been determined for a number of bacteriocins, but most remain incompletely characterized. These gene-encoded peptides are amenable to bioengineering strategies and heterologous expression, enabling metagenomic mining and modification of novel antimicrobials. The ongoing global antimicrobial resistance crisis demands that novel therapeutics be developed to combat infectious pathogens. New compounds that are target-specific and compatible with the resident microbiota would be valuable alternatives to current antimicrobials. As bacteriocins can be broad or narrow spectrum in nature, they are promising tools for this purpose. However, few bacteriocins have gone beyond preclinical trials and none is currently used therapeutically in humans. In this Review, we explore the broad diversity in bacteriocin structure and function, describe identification and optimization methods and discuss the reasons behind the lack of translation beyond the laboratory of these potentially valuable antimicrobials.