Imperial College London

DrJamesAbbott

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Honorary Research Officer
 
 
 
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Contact

 

+44 (0)20 7594 5149j.abbott Website

 
 
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Location

 

126Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

41 results found

Kalamara M, Abbott JC, MacPhee CE, Stanley-Wall NRet al., 2021, Biofilm hydrophobicity in environmental isolates of Bacillus subtilis., Microbiology (Reading), Vol: 167

Biofilms are communities of bacteria that are attached to a surface and surrounded by an extracellular matrix. The extracellular matrix protects the community from stressors in the environment, making biofilms robust. The Gram-positive soil bacterium Bacillus subtilis, particularly the isolate NCIB 3610, is widely used as a model for studying biofilm formation. B. subtilis NCIB 3610 forms colony biofilms that are architecturally complex and highly hydrophobic. The hydrophobicity is linked, in part, to the localisation of the protein BslA at the surface of the biofilm, which provides the community with increased resistance to biocides. As most of our knowledge about B. subtilis biofilm formation comes from one isolate, it is unclear if biofilm hydrophobicity is a widely distributed feature of the species. To address this knowledge gap, we collated a library of B. subtilis soil isolates and acquired their whole genome sequences. We used our novel isolates to examine biofilm hydrophobicity and found that, although BslA is encoded and produced by all isolates in our collection, hydrophobicity is not a universal feature of B. subtilis colony biofilms. To test whether the matrix exopolymer poly γ-glutamic acid could be masking hydrophobicity in our hydrophilic isolates, we constructed deletion mutants and found, contrary to our hypothesis, that the presence of poly γ-glutamic acid was not the reason for the observed hydrophilicity. This study highlights the natural variation in the properties of biofilms formed by different isolates and the importance of using a more diverse range of isolates as representatives of a species.

Journal article

Kalamara M, Abbott JC, MacPhee CE, Stanley-Wall NRet al., 2021, Biofilm hydrophobicity in environmental isolates of Bacillus subtilis

<jats:title>Abstract</jats:title><jats:p>Biofilms are communities of bacteria that are attached to a surface and surrounded by an extracellular matrix. The extracellular matrix protects the community from stressors in the environment, making biofilms robust. The Gram-positive soil bacterium <jats:italic>Bacillus subtilis</jats:italic>, particularly the isolate NCIB 3610, is widely used as a model for studying biofilm formation. <jats:italic>B. subtilis</jats:italic> NCIB 3610 forms colony biofilms that are architecturally complex and highly hydrophobic. The hydrophobicity is linked, in part, to the localisation of the protein BslA at the surface of the biofilm, which provides the community with increased resistance to biocides. As most of our knowledge about <jats:italic>B. subtilis</jats:italic> biofilm formation comes from one isolate, it is unclear if biofilm hydrophobicity is a widely distributed feature of the species. To address this knowledge gap, we collated a library of <jats:italic>B. subtilis</jats:italic> soil isolates and acquired their whole genome sequences. We used our new isolates to examine biofilm hydrophobicity and found that, although BslA is encoded and produced by all isolates in our collection, hydrophobicity is not a universal feature of <jats:italic>B. subtilis</jats:italic> colony biofilms. To test whether the matrix exopolymer poly γ-glutamic acid could be masking hydrophobicity in our hydrophilic isolates, we constructed deletion mutants and found, contrary to our hypothesis, that the presence of poly γ-glutamic acid was not the reason behind the observed hydrophilicity. This study highlights the natural variation in the properties of biofilms formed by different isolates and the importance of using a more diverse range of isolates as representatives of a species.</jats:p><jats:sec><jats:title>Repositories</jats:title><jat

Journal article

Robertson-Albertyn S, Concas F, Brown LH, Orr JN, Abbott JC, George TS, Bulgarelli Det al., 2021, A genome-annotated bacterial collection of the barley rhizosphere microbiota

<jats:title>ABSTRACT</jats:title><jats:p>We generated a bacterial collection from the rhizosphere of cultivated barley (<jats:italic>Hordeum vulgare</jats:italic> L. ssp. <jats:italic>vulgare</jats:italic>) to assess taxonomic distribution of culturable members of the barley microbiota and their plant growth-promoting potential. From this we retrieved strains belonging to the dominant phyla of the plant microbiota— Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria—and gathered evidence they code for functional genes implicated in nitrogen fixation, hydrogen cyanide channels and phosphate solubilisation. Here we present an initial comparative genomic analysis of the collection revealing that plant growth-promoting potential of the culturable barley bacterial microbiota appears to have a relatively broad phylogenetic base while retaining some strain-specificity.</jats:p>

Journal article

Butterfield ER, Abbott JC, Field MC, 2021, Automated Phylogenetic Analysis Using Best Reciprocal BLAST., Methods Mol Biol, Vol: 2369, Pages: 41-63

Reconstruction of the evolutionary history of specific protein-coding genes is an essential component of the biological sciences toolkit and relies on identification of orthologs (a gene in different organisms related by vertical descent from a common ancestor and usually presumed to have the same or similar function) and paralogs (a gene related to another in the same organism by descent from a single ancestral gene which may, or may not, retain the same/similar function) across a range of taxa. While obviously essential for the reconstruction of evolutionary histories, ortholog identification is of importance for protein expression, modeling for drug discovery programs, identification of critical residues and other studies. Here we describe an automated system for searching for orthologs and paralogs in eukaryotic organisms. Unlike manual methods the system is fast, requiring minimal user input while still being highly configurable.

Journal article

Maver M, Escudero-Martinez C, Abbott J, Morris J, Hedley PE, Mimmo T, Bulgarelli Det al., 2020, Applications of the indole-alkaloid gramine shape the prokaryotic microbiota thriving at the barley root-soil interface

<jats:title>Abstract</jats:title><jats:p>Microbial communities proliferating at the root-soil interface, collectively referred to as the rhizosphere microbiota, represent an untapped beneficial resource for plant growth, development and health. Integral to a rational manipulation of the microbiota for sustainable agriculture is the identification of the molecular determinants of these communities. In plants, biosynthesis of allelochemicals is centre stage in defining inter-organismal relationships in the environment. Intriguingly, this process has been moulded by domestication and breeding selection. The indole-alkaloid gramine, whose occurrence in barley (<jats:italic>Hordeum vulgare</jats:italic> L.) is widespread among wild genotypes but has been counter selected in several modern varieties, is a paradigmatic example of this phenomenon. This prompted us to investigate how exogenous applications of gramine impacted on the rhizosphere microbiota of two, gramine-free, elite barley varieties grown in a reference agricultural soil. High throughput 16S rRNA gene amplicon sequencing revealed that applications of gramine interfere with the proliferation of a subset of soil microbes with a relatively broad phylogenetic assignment. Strikingly, growth of these bacteria appeared to be rescued by barley plants in a genotype- and dosage-independent manner. In parallel, we discovered that host recruitment cues can interfere with the impact of gramine application in a host genotype-dependent manner. Interestingly, this latter effect displayed a bias for members of the phyla Proteobacteria. These initial observations indicate that gramine can act as a determinant of the prokaryotic communities inhabiting the root-soil interface.</jats:p>

Journal article

Hsu C-Y, Cairns L, Hobley L, Abbott J, O'Byrne C, Stanley-Wall NRet al., 2020, Genomic Differences between Listeria monocytogenes EGDe Isolates Reveal Crucial Roles for SigB and Wall Rhamnosylation in Biofilm Formation, JOURNAL OF BACTERIOLOGY, Vol: 202, ISSN: 0021-9193

Journal article

Elias MS, Wright SC, Remenyi J, Abbott JC, Bray SE, Cole C, Edwards S, Gierlinski M, Glok M, McGrath JA, Nicholson WV, Paternoster L, Prescott AR, Ten Have S, Whitfield PD, Lamond AI, Brown SJet al., 2019, EMSY expression affects multiple components of the skin barrier with relevance to atopic dermatitis, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 144, Pages: 470-481, ISSN: 0091-6749

Journal article

Arnaouteli S, Matoz-Fernandez DA, Porter M, Kalamara M, Abbott J, MacPhee CE, Davidson FA, Stanley-Wall NRet al., 2019, Pulcherrimin formation controls growth arrest of the Bacillus subtilis biofilm, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 116, Pages: 13553-13562, ISSN: 0027-8424

Journal article

Terrazas RA, Robertson-Albertyn S, Corral AM, Escudero-Martinez C, Balbirnie-Cumming K, Morris J, Hedley PE, Paterson E, Baggs EM, Abbott J, Bulgarelli Det al., 2019, Nitrogen availability modulates the host control of the barley rhizosphere microbiota

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Since the dawn of agriculture, human selection on plants has progressively differentiated input-demanding productive crops from their wild progenitors thriving in marginal areas. Barley (<jats:italic>Hordeum vulgare</jats:italic>), the fourth most cultivated cereal globally, is a prime example of this process. We previously demonstrated that wild and domesticated barley genotypes host distinct microbial communities in their rhizosphere. Here, we tested the hypothesis that microbiota diversification is modulated by, and responds to, nitrogen (N) application in soil and assessed the impact of microbiota taxonomic and functional compositions on plant growth.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We grew two wild (<jats:italic>H. vulgare</jats:italic> ssp. <jats:italic>spontaneum</jats:italic>) and an ‘Elite’ domesticated (<jats:italic>H. vulgare</jats:italic> ssp. <jats:italic>vulgare</jats:italic>) barley genotypes in an agricultural soil treated with and without N inputs. By using a two-pronged 16S rRNA gene amplicon sequencing and comparative metagenomics approach, we determined the impact of N application on taxonomic composition and metabolic potential of the microbial communities exposed to limiting and replete N supplies. We then implemented a plant-soil feedback experiment to assess microbiotas’ recruitment cues and contribution to plant growth.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>N availability emerged as a modulator of the recruitment cues of the barley bacterial microbiota as evidenced by the increased number of bacterial genera differentially recruited between unplanted soil and rhizosphere communities under N-limiting conditio

Journal article

Arnaouteli S, Matoz-Fernandez D, Porter M, Kalamara M, Abbott J, MacPhee CE, Davidson FA, Stanley-Wall NRet al., 2019, Pulcherrimin formation controls growth arrest of theBacillus subtilisbiofilm

<jats:title>Abstract</jats:title><jats:p>Biofilm formation by<jats:italic>Bacillus subtilis</jats:italic>is a communal process that culminates in the formation of architecturally complex multicellular communities. Here we reveal that the transition of the biofilm into a non-expanding phase constitutes a distinct step in the process of biofilm development. Using genetic analysis we show that<jats:italic>B. subtilis</jats:italic>strains lacking the ability to synthesize pulcherriminic acid form biofilms that sustain the expansion phase, thereby linking pulcherriminic acid to growth arrest. However, production of pulcherriminic acid is not sufficient to block expansion of the biofilm. It needs to be secreted into the extracellular environment where it chelates Fe<jats:sup>3+</jats:sup>from the growth medium in a non-enzymatic reaction. Utilizing mathematical modelling and a series of experimental methodologies we show that when the level of freely available iron in the environment drops below a critical threshold, expansion of the biofilm stops. Bioinformatics analysis allows us to identify the genes required for pulcherriminic acid synthesis in other Firmicutes but the patchwork presence both within and across closely related species suggests loss of these genes through multiple independent recombination events. The seemingly counterintuitive self-restriction of growth led us to explore if there were any benefits associated pulcherriminic acid production. We identified that pulcherriminic acid producers can prevent invasion from neighbouring communities through the generation of an “iron free” zone thereby addressing the paradox of pulcherriminic acid production by<jats:italic>B. subtilis</jats:italic>.</jats:p><jats:sec><jats:title>Significance</jats:title><jats:p>Understanding the processes that underpin the mechanism of biofilm formation, dispersal, and inhib

Journal article

Hoyles L, Fernandez-Real J-M, Federici M, Serino M, Abbott J, Charpentier J, Heymes C, Luque JL, Anthony E, Barton RH, Chilloux J, Myridakis A, Martinez-Gili L, Moreno-Navarrete JM, Benhamed F, Azalbert V, Blasco-Baque V, Puig J, Xifra G, Ricart W, Tomlinson C, Woodbridge M, Cardellini M, Davato F, Cardolini I, Porzio O, Gentileschi P, Lopez F, Foufelle F, Butcher SA, Holmes E, Nicholson JK, Postic C, Burcelin R, Dumas M-Eet al., 2018, Publisher Correction: Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women, Nature Medicine, Vol: 24, Pages: 1628-1628, ISSN: 1078-8956

In the version of this article originally published, the received date was missing. It should have been listed as 2 January 2018. The error has been corrected in the HTML and PDF versions of this article.

Journal article

Hoyles L, Fernández-Real JM, Federici M, Serino M, Abbott J, Charpentier J, Heymes C, Latorre Luque J, Anthony E, Barton RH, Chilloux J, Myridakis A, Martinez-Gili L, Moreno-Navarrete JM, Rayah F, Azalbert V, Blasco-Baque V, Puig J, Xifra G, Ricart W, Tomlinson C, Woodbridge M, Cardellini M, Davato F, Cardolini I, Porzio O, Gentilieschi P, Lopez F, Foufelle F, Butcher SA, Holmes E, Nicholson JK, Postic C, Burcelin R, Dumas MEet al., 2018, Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women, Nature Medicine, Vol: 24, Pages: 1-17, ISSN: 1078-8956

Hepatic steatosis is a multifactorial condition that is often observed in obese patients and is a prelude to non-alcoholic fatty liver disease. Here, we combine shotgun sequencing of fecal metagenomes with molecular phenomics (hepatic transcriptome and plasma and urine metabolomes) in two well-characterized cohorts of morbidly obese women recruited to the FLORINASH study. We reveal molecular networks linking the gut microbiome and the host phenome to hepatic steatosis. Patients with steatosis have low microbial gene richness and increased genetic potential for the processing of dietary lipids and endotoxin biosynthesis (notably from Proteobacteria), hepatic inflammation and dysregulation of aromatic and branched-chain amino acid metabolism. We demonstrated that fecal microbiota transplants and chronic treatment with phenylacetic acid, a microbial product of aromatic amino acid metabolism, successfully trigger steatosis and branched-chain amino acid metabolism. Molecular phenomic signatures were predictive (area under the curve = 87%) and consistent with the gut microbiome having an effect on the steatosis phenome (>75% shared variation) and, therefore, actionable via microbiome-based therapies.

Journal article

Singh GKJ, Kaye S, Abbott JC, Boesecke C, Rockstroh J, McClure MO, Nelson Met al., 2018, Use of next-generation sequencing in the CHAT study (acute HCV in HIV): effect of baseline resistance-associated NS3 variants on treatment failure, HIV CLINICAL TRIALS, Vol: 19, Pages: 46-51, ISSN: 1528-4336

Journal article

Hoyles L, Fernández-Real JM, Federici M, Serino M, Azalbert V, Blasco V, Abbott J, Barton RH, Puig J, Xifra G, Ricart W, Woodbridge M, Tomlinson C, Cardellini M, Davato F, Cardolini I, Porzio O, Gentilieschi P, Lopez F, Foufelle F, Postic C, Butcher SA, Holmes E, Nicholson JK, Burcelin R, Dumas MEet al., 2017, Integrated systems biology to study the contribution of the gut microbiome to steatosis in obese women, Exploring Human Host-Microbiome Interactions in Health and Disease

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease, increasing in worldwide prevalence as a result of the obesity epidemic. It manifests in hepatic cells as steatosis with or without lobular inflammation and/or ballooning. Animal and human studies have suggested the gut microbiome contributes to steatosis/NAFLD. The aim of this study was to use an integrated approach with various -omics and clinical data to evaluate the contribution of the gut microbiome to the molecular phenome (hepatic transcriptome, metabonome) of steatosis. Metagenomic (faecal microbiome), transcriptomic (liver biopsy), metabonomic (plasma and urine, 1H-NMR) and clinical data were collected for 56 morbidly obese (BMI >35) women from Italy (n = 31) and Spain (n = 25) who elected for bariatric surgery. Confounder analyses of clinical data were done using linear modelling. Histological examination of liver biopsies was used to grade steatosis. Faecal metagenomes were generated and analysed using the SCalable Automated Metagenomics Pipeline (SCAMP). Differentially expressed genes were identified in hepatic transcriptomes, and analysed using a range of different bioinformatics tools. 1H-NMR data were generated for plasma and urinary metabonomes. Clinical, metagenomic, transcriptomic and metabonomic data were integrated in the context of steatosis using partial Spearman's correlation, taking confounders (age, body mass index and cohort) into account. Steatosis was anti-correlated with microbial gene richness, and correlated with abundance of Proteobacteria. KEGG analyses of metagenomic data suggested increased microbial processing of dietary lipids and amino acids, as well as endotoxin-related processes related to Proteobacteria. Steatosis-associated hepatic transcriptomes were associated with branched-chain amino acid (BCAA) metabolism, endoplasmic reticulum/phagosome, and immune responses associated with non-specific microbial infections. Metabonom

Poster

Hoyles L, Fernández-Real JM, Federici M, Serino M, Azalbert V, Blasco V, Abbott J, Barton RH, Puig J, Xifra G, Ricart W, Woodbridge M, Tomlinson C, Cardellini M, Davato F, Cardolini I, Porzio O, Gentilieshci P, Lopez F, Foufelle F, Postic C, Butcher SA, Holmes E, Nicholson JK, Burcelin R, Dumas MDet al., 2017, Integrated systems biology to study non-alcoholic fatty liver disease in obese women, International Scientific Association for Probiotics and Prebiotics

Metagenomic (faecal microbiome), transcriptomic (liver biopsy), metabonomic (plasma and urine, 1H-NMR) and clinical (28 variables) data were collected for 56 morbidly obese (BMI >35) women from Italy (n = 31) and Spain (n = 25) who elected for bariatric surgery. Data were integrated to evaluate the contribution of the gut microbiome to the molecular phenome (hepatic transcriptome, plasma and urine metabonome) of NAFLD independent of clinical confounders (age, BMI, cohort) using partial Spearman’s correlation. NAFLD activity score (NAS) was anti-correlated with microbial gene richness, and correlated with abundance of Proteobacteria. KEGG analyses of metagenomic data suggested increased microbial processing of dietary lipids and amino acids, as well as endotoxin-related processes related to Proteobacteria. Metabonomic profiles highlighted imbalances in choline metabolism, branched-chain amino acid (BCAA) metabolism and gut-derived microbial metabolites resulting from metabolism of amino acids. NAFLD-associated hepatic transcriptomes were associated with BCAA metabolism, endoplasmic reticulum/phagosome, and immune responses associated with non-specific microbial infections. Molecular phenomic signatures were stable and predictive regardless of sample size, and consistent with the microbiome making a significant contribution to the NAFLD phenome. There is disruption of the gut– liver axis in NAFLD, which can be seen in the gut microbiome, hepatic transcriptome and urinary and plasma metabonomes. Consistency of phenome signatures strongly supports a relationship between microbial amino acid metabolism and microbial gene richness, hepatic gene expression and biofluid metabonomes, and ultimately NAS.

Poster

Hoyles L, Fernandez-Real JM, Federici M, Serino M, Azalbert V, Blasco V, Abbott J, Barton RH, Puig J, Xifra G, Ricart W, Woodbridge M, Tomlinson C, Cardelini M, Davato F, Cardolini I, Porzio O, Gentilieschi P, Lopez F, Foufelle F, Postic C, Butcher SA, Holmes E, Nicholson JK, Burcenlin R, Dumas MEet al., 2017, Integrated systems biology to study non-alcoholic fatty liver disease in obese women, Tranlsational Bioinformatics

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition and one of the most common causes of chronic liver disease, with increasing worldwide prevalence. Microbiome-associated lipopolysaccharides (LPS) are associated with NAFLD in rodent models, but their relevance in human liver disease is not understood. In addition, microbiome-driven degradation of dietary choline – and its subsequent removal from host-associated metabolic processes – is thought to contribute to development of NAFLD. The FLORINASH study set out to determine the contribution of the gut microbiome to the NAFLD-associated molecular phenome (transcriptome, metabonome) independent of clinical confounders.Morbidly obese women [body mass index (BMI) >35] from Italy (n = 31) and Spain (n = 25) who elected for bariatric surgery were recruited to the study. Clinical data (28 variables) were recorded. Faecal samples, liver biopsies, blood and urine samples were collected. Faecal metagenomes were analysed using an in-house metagenomics pipeline (SCaleble Automated Metagenomics Pipeline). NAFLD activity score (NAS; 0, 1, 2, 3) was determined by histological examination of liver biopsies. Differentially expressed genes in hepatic transcriptomes were identified, and analysed using several complementary tools. 1H-NMR data were generated for plasma and urinary metabonomes. Clinical, metagenomic, transcriptomic and metabonomic data were integrated using partial Spearman’s correlation, taking identified confounders (age, BMI and cohort) into account.NAS was anti-correlated with microbial gene richness, and correlated with abundance of Gram-negative Proteobacteria. KEGG analyses of metagenomic data suggested increased microbial processing of dietary lipids and amino acids, as well as LPS-related processes associated with Proteobacteria in NAFLD. Activation of immune responses associated with Gram-negative (LPS-associated) microbial infections was correlated with NAS in hepatic tr

Poster

JC A, 2017, BugBuilder - An Automated Microbial Genome Assembly and Analysis Pipeline

<jats:title>Abstract</jats:title><jats:sec><jats:title>Summary</jats:title><jats:p>BugBuilder is a framework for hands-free assembly and annotation of microbial genomes. It produces outputs suitable either for database submission or downstream finishing processes. It is configurable to work with most command-line assembly and scaffolding tools which are selectable at run-time, and supports all common sequence types used in microbial genome assembly.</jats:p></jats:sec><jats:sec><jats:title>Availability and Implementation</jats:title><jats:p>BugBuilder is implemented in Perl and is available under the Artistic License from <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.imperial.ac.uk/bioinformatics-data-science-group/resources/software/bugbuilder,">http://www.imperial.ac.uk/bioinformatics-data-science-group/resources/software/bugbuilder,</jats:ext-link> A virtual machine image is available pre-configured with the relevant freely-redistributable dependencies.</jats:p></jats:sec><jats:sec><jats:title>Contact</jats:title><jats:p><jats:email>j.abbott@imperial.ac.uk</jats:email></jats:p></jats:sec>

Journal article

Hoyles L, Fernández-Real JM, Federici M, Serino M, Azalbert V, Blasco V, Abbott J, Barton RH, Puig J, Xifra G, Ricart W, Woodbridge M, Tomlinson C, Cardellini M, Davato F, Cardolini I, Porzio O, Gentilieschi P, Lopez F, Foufelle F, Postic C, Butcher SA, Holmes E, Nicholson JK, Burcelin R, Dumas MEet al., 2017, Integrated systems biology to study non-alcoholic fatty liver disease in obese women, Gut Microbiota for Health World Summit 2017

Objectives: To integrate metagenomic (faecal microbiome), transcriptomic, metabonomic and clinical data to evaluate the contribution of the gut microbiome to the molecular phenome (hepatic transcriptome, plasma and urine metabonome) of non-alcoholic fatty liver disease (NAFLD) independent of clinical confounders in morbidly obese women recruited to the FLORINASH study.Methods: Faecal, liver biopsy, blood and urine samples and data for 28 clinical variables were collected for 56 obese [body mass index (BMI) >35] women from Italy (n = 31) and Spain (n = 25) who elected for bariatric surgery. Confounder analyses of clinical data were done using linear modeling. Histological examination of liver biopsies was used to grade NAFLD (NAFLD activity score: 0, 1, 2, 3). Faecal metagenomes were generated and analysed using the Imperial Metagenomics Pipeline. Differentially expressed genes were identified in hepatic transcriptomes, and analysed using Enrichr, network analyses and Signaling Pathway Impact Analysis. 1H-NMR data were generated for plasma and urinary metabonomes. Clinical, metagenomic, transcriptomic and metabonomic data were integrated using partial Spearman’s correlation, taking confounders (age, body mass index and cohort) into account.Results: NAFLD activity score was anti-correlated with microbial gene richness, and correlated with abundance of Proteobacteria. KEGG analyses of metagenomic data suggested increased microbial processing of dietary lipids and amino acids, as well as endotoxin-related processes related to Proteobacteria. Metabonomic profiles highlighted imbalances in choline metabolism, branched-chain amino acid metabolism and gut-derived microbial metabolites resulting from metabolism of amino acids. NAFLD-associated hepatic transcriptomes were associated with branched-chain amino acid metabolism, endoplasmic reticulum/phagosome, and immune responses associated with microbial infections. Molecular phenomic signatures were stable and predic

Poster

Hoyles L, Fernández-Real JM, Federici M, Serino M, Azalbert V, Blasco V, Abbott J, Barton RH, Puig J, Xifra G, Ricart W, Woodbridge M, Tomlinson C, Cardellini M, Davato F, Cardolini I, Porzio O, Gentilieschi P, Lopez F, Foufelle F, Postic C, Butcher SA, Holmes E, Nicholson JK, Burcelin R, Dumas MEet al., 2017, Integrated systems biology to study non-alcoholic fatty liver disease in obese women, MRC-PHE Centre for Environment & Health - Centre Training Programme Annual Meeting

Poster

Florea M, Hagemann H, Santosa G, Abbott J, Micklem CN, Spencer-Milnes X, de Arroyo Garcia L, Paschou D, Lazenbatt C, Kong D, Chughtai H, Jensen K, Freemont P, Kitney RI, Reeve B, Ellis Tet al., 2016, Engineering control of bacterial cellulose production using a genetic toolkit and a new cellulose-producing strain, Proceedings of the National Academy of Sciences of the United States of America, Vol: 113, Pages: E3431-E3440, ISSN: 0027-8424

Bacterial cellulose is a strong and ultrapure form of cellulose produced naturally by several species of the Acetobacteraceae. Its high strength, purity and biocompatibility make it of great interest to materials science, however precise control of its biosynthesis has remained a challenge for biotechnology. Here we isolate a new strain of Komagataeibacter rhaeticus (Komagataeibacter rhaeticus iGEM) that can produce cellulose at high yields, grow in low nitrogen conditions, and is highly resistant to toxic chemicals. We achieve external control over its bacterial cellulose production through development of a modular genetic toolkit that enables rational reprogramming of the cell. To further its use as an organism for biotechnology, we sequenced its genome and demonstrate genetic circuits that enable functionalization and patterning of heterologous gene expression within the cellulose matrix. This work lays the foundations for using genetic engineering to produce cellulose-based materials, with numerous applications in basic science, materials engineering and biotechnology.

Journal article

Florea M, Reeve B, Abbott J, Freemont PS, Ellis Tet al., 2016, Genome sequence and plasmid transformation of the model high-yield bacterial cellulose producer Gluconacetobacter hansenii ATCC 53582., Scientific Reports, Vol: 6, ISSN: 2045-2322

Bacterial cellulose is a strong, highly pure form of cellulose that is used in a range of applications in industry, consumer goods and medicine. Gluconacetobacter hansenii ATCC 53582 is one of the highest reported bacterial cellulose producing strains and has been used as a model organism in numerous studies of bacterial cellulose production and studies aiming to increased cellulose productivity. Here we present a high-quality draft genome sequence for G. hansenii ATCC 53582 and find that in addition to the previously described cellulose synthase operon, ATCC 53582 contains two additional cellulose synthase operons and several previously undescribed genes associated with cellulose production. In parallel, we also develop optimized protocols and identify plasmid backbones suitable for transformation of ATCC 53582, albeit with low efficiencies. Together, these results provide important information for further studies into cellulose synthesis and for future studies aiming to genetically engineer G. hansenii ATCC 53582 for increased cellulose productivity.

Journal article

Abbott J, 2016, BugBuilder

BugBuilder is a pipeline for hands-free assembly and analysis of microbial genome sequences. It produces outputs suitable either for direct submission to sequence databases or for use in downstream finishing processes. It is configurable to work with most command-line assembly and scaffolding tools which are selectable at run-time, and supports all common sequence types used in microbial genome assembly.

Software

Kato N, Loh M, Takeuchi F, Verweij N, Wang X, Zhang W, Kelly TN, Saleheen D, Lehne B, Leach IM, Drong AW, Abbott J, Wahl S, Tan S-T, Scott WR, Campanella G, Chadeau-Hyam M, Afzal U, Ahluwalia TS, Bonder MJ, Chen P, Dehghan A, Edwards TL, Esko T, Go MJ, Harris SE, Hartiala J, Kasela S, Kasturiratne A, Khor C-C, Kleber ME, Li H, Mok ZY, Nakatochi M, Sapari NS, Saxena R, Stewart AFR, Stolk L, Tabara Y, Teh AL, Wu Y, Wu J-Y, Zhang Y, Aits I, Alves ADSC, Das S, Dorajoo R, Hopewell JC, Kim YK, Koivula RW, Luan J, Lyytikainen L-P, Nguyen QN, Pereira MA, Postmus I, Raitakari OT, Bryan MS, Scott RA, Sorice R, Tragante V, Traglia M, White J, Yamamoto K, Zhang Y, Adair LS, Ahmed A, Akiyama K, Asif R, Aung T, Barroso I, Bjonnes A, Braun TR, Cai H, Chang L-C, Chen C-H, Cheng C-Y, Chong Y-S, Collins R, Courtney R, Davies G, Delgado G, Do LD, Doevendans PA, Gansevoort RT, Gao Y-T, Grammer TB, Grarup N, Grewal J, Gu D, Wander GS, Hartikainen A-L, Hazen SL, He J, Heng C-K, Hixson JE, Hofman A, Hsu C, Huang W, Husemoen LLN, Hwang J-Y, Ichihara S, Igase M, Isono M, Justesen JM, Katsuy T, Kibriya MG, Kim YJ, Kishimoto M, Koh W-P, Kohara K, Kumari M, Kwek K, Lee NR, Lee J, Liao J, Lieb W, Liewald DCM, Matsubara T, Matsushita Y, Meitinger T, Mihailov E, Milani L, Mills R, Mononen N, Mueller-Nurasyid M, Nabika T, Nakashima E, Ng HK, Nikus K, Nutile T, Ohkubo T, Ohnaka K, Parish S, Paternoster L, Peng H, Peters A, Pham ST, Pinidiyapathirage MJ, Rahman M, Rakugi H, Rolandsson O, Rozario MA, Ruggiero D, Sala CF, Sarju R, Shimokawa K, Snieder H, Sparso T, Spiering W, Starr JM, Stott DJ, Stram DO, Sugiyama T, Szymczak S, Tang WHW, Tong L, Trompet S, Turjanmaa V, Ueshima H, Uitterlinden AG, Umemura S, Vaarasmaki M, van Dam RM, van Gilst WH, van Veldhuisen DJ, Viikari JS, Waldenberger M, Wang Y, Wang A, Wilson R, Wong T-Y, Xiang Y-B, Yamaguchi S, Ye X, Young RD, Young TL, Yuan J-M, Zhou X, Asselbergs FW, Ciullo M, Clarke R, Deloukas P, Franke A, Franks PW, Franks S, Friedlander Y, Gross MD, Guoet al., 2015, Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation, Nature Genetics, Vol: 47, Pages: 1282-1293, ISSN: 1546-1718

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

Journal article

Turner CE, Abbott J, Lamagni T, Holden MTG, David S, Jones MD, Game L, Efstratiou A, Sriskandan Set al., 2015, Emergence of a new highly successful acapsular group A Streptococcus clade of the genotype emm89 in the United Kingdom, mBio, Vol: 6, ISSN: 2161-2129

Group A Streptococcus (GAS) genotype emm89 is increasingly recognized as a leading cause of disease worldwide, yet factors that underlie the success of this emm type are unknown. Surveillance identified a sustained nationwide increase in emm89 invasive GAS disease in the United Kingdom, prompting longitudinal investigation of this genotype. Whole-genome sequencing revealed a recent dramatic shift in the emm89 population with the emergence of a new clade that increased to dominance over previous emm89 variants. Temporal analysis indicated that the clade arose in the early 1990s but abruptly increased in prevalence in 2008, coinciding with an increased incidence of emm89 infections. Although standard variable typing regions (emm subtype, tee type, sof type, and multilocus sequence typing [MLST]) remained unchanged, uniquely the emergent clade had undergone six distinct regions of homologous recombination across the genome compared to the rest of the sequenced emm89 population. Two of these regions affected known virulence factors, the hyaluronic acid capsule and the toxins NADase and streptolysin O. Unexpectedly, and in contrast to the rest of the sequenced emm89 population, the emergent clade-associated strains were genetically acapsular, rendering them unable to produce the hyaluronic acid capsule. The emergent clade-associated strains had also acquired an NADase/streptolysin O locus nearly identical to that found in emm12 and modern emm1 strains but different from the rest of the sequenced emm89 population. The emergent clade-associated strains had enhanced expression of NADase and streptolysin O. The genome remodeling in the new clade variant and the resultant altered phenotype appear to have conferred a selective advantage over other emm89 variants and may explain the changes observed in emm89 GAS epidemiology.

Journal article

Hoyles L, Abbott JC, Holmes E, Nicholson JK, Dumas ME, Butcher SAet al., 2015, IMP: Imperial Metagenomics Pipeline for high-­throughput sequence data, Exploring Human Host-Microbiome Interactions in Health and Disease

Poster

Chambers JC, Loh M, Lehne B, Drong A, Kriebel J, Motta V, Wahl S, Elliott HR, Rota F, Scott WR, Zhang W, Tan S-T, Campanella G, Chadeau-Hyam M, Yengo L, Richmond RC, Adamowicz-Brice M, Afzal U, Bozaoglu K, Mok ZY, Ng HK, Pattou F, Prokisch H, Rozario MA, Tarantini L, Abbott J, Ala-Korpela M, Albetti B, Ammerpohl O, Bertazzi PA, Blancher C, Caiazzo R, Danesh J, Gaunt TR, de Lusignan S, Gieger C, Illig T, Jha S, Jones S, Jowett J, Kangas AJ, Kasturiratne A, Kato N, Kotea N, Kowlessur S, Pitkaeniemi J, Punjabi P, Saleheen D, Schafmayer C, Soininen P, Tai E-S, Thorand B, Tuomilehto J, Wickremasinghe AR, Kyrtopoulos SA, Aitman TJ, Herder C, Hampe J, Cauchi S, Relton CL, Froguel P, Soong R, Vineis P, Jarvelin M-R, Scott J, Grallert H, Bollati V, Elliott P, McCarthy MI, Kooner JSet al., 2015, Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study, The Lancet Diabetes & Endocrinology, Vol: 3, Pages: 526-534, ISSN: 2213-8587

BackgroundIndian Asians, who make up a quarter of the world's population, are at high risk of developing type 2 diabetes. We investigated whether DNA methylation is associated with future type 2 diabetes incidence in Indian Asians and whether differences in methylation patterns between Indian Asians and Europeans are associated with, and could be used to predict, differences in the magnitude of risk of developing type 2 diabetes.MethodsWe did a nested case-control study of DNA methylation in Indian Asians and Europeans with incident type 2 diabetes who were identified from the 8-year follow-up of 25 372 participants in the London Life Sciences Prospective Population (LOLIPOP) study. Patients were recruited between May 1, 2002, and Sept 12, 2008. We did epigenome-wide association analysis using samples from Indian Asians with incident type 2 diabetes and age-matched and sex-matched Indian Asian controls, followed by replication testing of top-ranking signals in Europeans. For both discovery and replication, DNA methylation was measured in the baseline blood sample, which was collected before the onset of type 2 diabetes. Epigenome-wide significance was set at p<1 × 10−7. We compared methylation levels between Indian Asian and European controls without type 2 diabetes at baseline to estimate the potential contribution of DNA methylation to increased risk of future type 2 diabetes incidence among Indian Asians.Findings1608 (11·9%) of 13 535 Indian Asians and 306 (4·3%) of 7066 Europeans developed type 2 diabetes over a mean of 8·5 years (SD 1·8) of follow-up. The age-adjusted and sex-adjusted incidence of type 2 diabetes was 3·1 times (95% CI 2·8–3·6; p<0·0001) higher among Indian Asians than among Europeans, and remained 2·5 times (2·1–2·9; p<0·0001) higher after adjustment for adiposity, physical activity, family history of type 2 diabetes, and baselin

Journal article

Chambers JC, Abbott J, Zhang W, Turro E, Scott WR, Tan S-T, Afzal U, Afaq S, Loh M, Lehne B, O'Reilly P, Gaulton KJ, Pearson RD, Li X, Lavery A, Vandrovcova J, Wass MN, Miller K, Sehmi J, Oozageer L, Kooner IK, Al-Hussaini A, Mills R, Grewal J, Panoulas V, Lewin AM, Northwood K, Wander GS, Geoghegan F, Li Y, Wang J, Aitman TJ, McCarthy MI, Scott J, Butcher S, Elliott P, Kooner JSet al., 2014, The South Asian Genome, PLOS One, Vol: 9, ISSN: 1932-6203

The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.

Journal article

Filippis I, Lopez-Cobollo R, Abbott J, Butcher S, Bishop GJet al., 2013, Using a periclinal chimera to unravel layer-specific gene expression in plants, PLANT JOURNAL, Vol: 75, Pages: 1039-1049, ISSN: 0960-7412

Journal article

Pedersen C, van Themaat E, McGuffin L, Abbott J, Burgis T, Barton G, Bindschedler L, Lu X, Maekawa T, WeSZling R, Cramer R, Thordal-Christensen H, Panstruga R, Spanu Pet al., 2012, Structure and evolution of barley powdery mildew effector candidates, BMC Genomics, Vol: 13, ISSN: 1471-2164

BACKGROUND:Protein effectors of pathogenicity are instrumental in modulating host immunity and disease resistance. The powdery mildew pathogen of grasses, Blumeria graminis, causes one of the most important diseases of cereal crops. B. graminis is an obligate biotrophic pathogen and as such has an absolute requirement to suppress or avoid host immunity to survive and cause disease.RESULTS:Here we characterise a superfamily predicted to be the full complement of Candidates for Secreted Effector Proteins (CSEPs) in the fungal barley powdery mildew parasite, B. graminis f.sp. hordei. The 491 genes encoding these proteins constitute over 7% of this pathogen’s annotated genes and most were grouped into 72 families of up to 59 members. They were predominantly expressed in the intracellular feeding structures, called haustoria, and proteins specifically associated with haustoria were identified by large-scale mass spectrometry-based proteomics. There are two major types of effector families: one comprises shorter proteins (100–150 amino acids), with a high relative expression level in the haustoria and evidence of extensive diversifying selection between paralogs; the second type consists of longer proteins (300–400 amino acids), with lower levels of differential expression and evidence of purifying selection between paralogs. An analysis of the predicted protein structures reveals polypeptide features that are similar to those of known fungal effectors, but also highlights unexpected structural affinities to ribonucleases throughout the entire effector superfamily. Candidate effector genes belonging to the same family are loosely clustered in the genome and are associated with repetitive DNA derived from retro-transposons.CONCLUSIONS:We employed the full complement of genomic, transcriptomic and proteomic analyses as well as structural prediction methods to identify and characterise the members of the CSEP superfamily in B. graminis f.sp. hordei. Based o

Journal article

Abbott JC, Butcher SA, 2012, Strategies towards sequencing complex crop genomes., Genome Biology, Vol: 13, ISSN: 1474-760X

A report on the Strategies for de novo assemblies of complex crop genomes workshop held at The Genome Analysis Centre, Norwich, UK, 8-10 October 2012.

Journal article

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