Dr Emma Laing

Featured Stories

Research Interests

My research focuses on exploiting -omics data to further understanding of bioloigcal systems. My research involves data mining, machine learning, data integration and the development of computational tools and algorithms.

Bioinformatic tools

Rank Products analysis online
 

Funding

£15k University of Surrey/RES competitively funded. 2016. 'Tissue/cell specificity in whole blood transcriptomic data', E Laing (PI), Y Jin, D J Dijk.

£94k Pirbright Institute/BBSRC PhD Studentship in collaboration with Merial Animal Health. 2015 - present. ‘Using a ‘Vaccinomics’ approach to investigate foot-and-mouth disease virus (FMDV) vaccine quality and characterise immune escape mechanisms’. D King (PI, Pirbright), G Freimanis (Pirbright), E Laing (Surrey).

£94k Pirbright Institute/BBSRC PhD Studentship. 2015 - present. ‘Investigation of the interaction of porcine reproductive and respiratory syndrome viruses with dendritic cells: implications for pathogenesis and immunity’. S Graham (PI, Pirbright), G Freimanis (Pirbright), R La Ragione (Surrey), E Laing (Surrey).

£3k University of Surrey/RES competitively funded. 2015. Industry-Surrey sandpit event on interdisciplinary sleep research, E Laing (PI), S Archer, D J Dijk.

£20k BBSRC (BB/N004086/1) Suite of modules comprising: Quantitative data analysis; Integrative interpretation of large-scale data; Systems modelling and network analysis. 2015. E Laing (PI), A Kierzek, S Warburton.

£454k BBSRC-European Space Agency (AO-13-BR). 2015 - present. ‘The effects of bedrest on the circadian organisation of the human blood transcriptome as a model for temporal dysregulation during long-term spaceflight and ageing’. S Archer (PI), D Dijk, E Laing, CP Smith, N Santhi.

£27k BBSRC partnership award (B/L02683X/1). 2014 - present. ‘Synthetic Biology for Bioenergy and Biotechnology’. C Avignone-Rossa (PI), E Laing.

£94k BBSRC iCASE PhD Studentship (BB/K01160X/1). 2014 - present.‘The development of a microbial community for increasing wheat crop yield’. Laing E (PI), Avignone-Rossa C, Hodgson S (Symbio Ltd).

£80k University of Surrey FHMS competitively awarded PhD Studentship, jointly funded by Leatherhead Food Research, 2012-present. ‘Understanding the factors involved in Campylobacter biofilm formation and survival. Laing E (PI), La Ragione RM.

£2k MILES (EPSRC) pump-priming funding.’ 2013. Genetic Algorithms and Fuzziness: From Biology to Aerospace’. Montomoli F, Laing E.

£80k University of Surrey competitively awarded FHMS & FEPS PhD Studentship, 2012-present. ‘Modelling for Predicting Antigenic Variability in Foot-and-Mouth Disease’. Laing E (PI), Jin Y.

£616k BBSRC (BB/J01916X/1), 2012- present. 'A study of metagenomics-informed biochemical functionality of microbial fuel cells using DDGS as a substrate'. M Bushell (PI), CA Avignone-Rossa, AM Kierzek, EE Laing, RCT Slade & J Varcoe.

£1.2 million AFOSR, 2008-2011. 'Cognitive vulnerabiliy following extended wakefullness in defined genotyps'. D-J Dijk (PI), J Groeger, S N Archer, M von Schantz, C P Smith & EE Laing

£1.76 million BBSRC (BB/F022883/1),  2008-2011. 'Circadian and homeostatic contributions to physiology, cognition and genome-wide expression in human and mouse variants of the PER3 VNTR polymorphism.' Named investigator.

Current funded PhD projects

Tameera Rahman (Co-supervisor, collaboration with Prof. Yaochu Jin):
Modelling for Predicting Antigenic Variability in Foot-and-Mouth Disease.
Jointly funded by the Department of Computing and FHMS (University of Surrey).

Rebecca Clarke (Principal supervisor, collaboration with Roberto La Ragione):
Understanding the factors involved in Campylobacter biofilm formation and survival
Jointly funded by Leatherhead Food Research and FHMS (University of Surrey).

David King (Co-supervisor, collaboration with Don King and Graham Freimanis, Pirbright Institute and colleagues in Merial):
Using a ‘Vaccinomics’ approach to investigate foot-and-mouth disease virus (FMDV) vaccine quality and characterise immune escape mechanisms
Funded by Pirbright Institute (BBSRC)

Research Collaborations

Dr. Simon Archer (FHMS, University of Surrey).
Dr. Claudio Avignone-Rossa (FHMS, University of Surrey).
Professor Mike Bushell (FHMS, University of Surrey).
Professor Derk-Jan Dijk (FHMS, University of Surrey).
Professor André Gerber (FHMS, University of Surrey).
Professor Yaochu Jin (FEPS, University of Surrey).
Professor Roberto La Ragione (FHMS, University of Surrey).
Professor Colin P Smith (FHMS, University of Surrey).
Symbio Ltd.

Teaching

BMS2036 Molecular Biology and Genetics 2

BMS3072 Systems Biology : Genomes in Action

MSc Medical Microbiology

MSc Veterinary Microbiology

Applied Systems Biology CPD modules

Departmental Duties

Senior PTY tutor for Microbiology, Veterinary Biosciences and Biological Sciences

Outgoing Erasmus officer for School of Biosciences

Exams officer for MSc Veterinary Biosciences

Member of Professional Training and Careers Committee (PTCC)

Module Organiser for BMS3072 : Systems Biology : Genomes in Action

Programme director of Applied Systems Biology suite of CPD modules

Contact Me

E-mail:
Phone: 01483 68 9626

Find me on campus
Room: 06 PGM 02

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My office hours

Mon-Fri by appointment 

Publications

Highlights

  • Matia-Gonzalez AM, Laing EE, Gerber AP. (2015) 'Conserved mRNA-binding proteomes in eukaryotic organisms'. NATURE PUBLISHING GROUP NATURE STRUCTURAL & MOLECULAR BIOLOGY, 22 (12), pp. 1027-1033.
  • Laing EE, Johnston JD, Möller-Levet CS, Bucca G, Smith CP, Dijk DJ, Archer SN. (2015) 'Exploiting human and mouse transcriptomic data: Identification of circadian genes and pathways influencing health'. BioEssays, 37 (5), pp. 544-556.
  • Romero DA, Hasan AH, Lin YF, Kime L, Ruiz-Larrabeiti O, Urem M, Bucca G, Mamanova L, Laing EE, van Wezel GP, Smith CP, Kaberdin VR, McDowall KJ. (2014) 'A comparison of key aspects of gene regulation in Streptomyces coelicolor and Escherichia coli using nucleotide-resolution transcription maps produced in parallel by global and differential RNA sequencing.'. Mol Microbiol,

    Abstract

    Streptomyces coelicolor is a model for studying bacteria renowned as the foremost source of natural products used clinically. Post-genomic studies have revealed complex patterns of gene expression and links to growth, morphological development and individual genes. However, the underlying regulation remains largely obscure, but undoubtedly involves steps after transcription initiation. Here we identify sites involved in RNA processing and degradation as well as transcription within a nucleotide-resolution map of the transcriptional landscape. This was achieved by combining RNA-sequencing approaches suited to the analysis of GC-rich organisms. Escherichia coli was analysed in parallel to validate the methodology and allow comparison. Previously, sites of RNA processing and degradation had not been mapped on a transcriptome-wide scale for E. coli. Through examples, we show the value of our approach and data sets. This includes the identification of new layers of transcriptional complexity associated with several key regulators of secondary metabolism and morphological development in S. coelicolor and the identification of host-encoded leaderless mRNA and rRNA processing associated with the generation of specialized ribosomes in E. coli. New regulatory small RNAs were identified for both organisms. Overall the results illustrate the diversity in mechanisms used by different bacterial groups to facilitate and regulate gene expression.

  • Archer SN, Laing EE, Möller-Levet CS, van der Veen DR, Bucca G, Lazar AS, Santhi N, Slak A, Kabiljo R, von Schantz M, Smith CP, Dijk DJ. (2014) 'Mistimed sleep disrupts circadian regulation of the human transcriptome.'. Proc Natl Acad Sci U S A,

    Abstract

    Circadian organization of the mammalian transcriptome is achieved by rhythmic recruitment of key modifiers of chromatin structure and transcriptional and translational processes. These rhythmic processes, together with posttranslational modification, constitute circadian oscillators in the brain and peripheral tissues, which drive rhythms in physiology and behavior, including the sleep-wake cycle. In humans, sleep is normally timed to occur during the biological night, when body temperature is low and melatonin is synthesized. Desynchrony of sleep-wake timing and other circadian rhythms, such as occurs in shift work and jet lag, is associated with disruption of rhythmicity in physiology and endocrinology. However, to what extent mistimed sleep affects the molecular regulators of circadian rhythmicity remains to be established. Here, we show that mistimed sleep leads to a reduction of rhythmic transcripts in the human blood transcriptome from 6.4% at baseline to 1.0% during forced desynchrony of sleep and centrally driven circadian rhythms. Transcripts affected are key regulators of gene expression, including those associated with chromatin modification (methylases and acetylases), transcription (RNA polymerase II), translation (ribosomal proteins, initiation, and elongation factors), temperature-regulated transcription (cold inducible RNA-binding proteins), and core clock genes including CLOCK and ARNTL (BMAL1). We also estimated the separate contribution of sleep and circadian rhythmicity and found that the sleep-wake cycle coordinates the timing of transcription and translation in particular. The data show that mistimed sleep affects molecular processes at the core of circadian rhythm generation and imply that appropriate timing of sleep contributes significantly to the overall temporal organization of the human transcriptome.

  • Möller-Levet CS, Archer SN, Bucca G, Laing EE, Slak A, Kabiljo R, Lo JC, Santhi N, von Schantz M, Smith CP, Dijk DJ. (2013) 'Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome.'. Proc Natl Acad Sci U S A, United States: 110 (12), pp. E1132-E1141.

    Abstract

    Insufficient sleep and circadian rhythm disruption are associated with negative health outcomes, including obesity, cardiovascular disease, and cognitive impairment, but the mechanisms involved remain largely unexplored. Twenty-six participants were exposed to 1 wk of insufficient sleep (sleep-restriction condition 5.70 h, SEM = 0.03 sleep per 24 h) and 1 wk of sufficient sleep (control condition 8.50 h sleep, SEM = 0.11). Immediately following each condition, 10 whole-blood RNA samples were collected from each participant, while controlling for the effects of light, activity, and food, during a period of total sleep deprivation. Transcriptome analysis revealed that 711 genes were up- or down-regulated by insufficient sleep. Insufficient sleep also reduced the number of genes with a circadian expression profile from 1,855 to 1,481, reduced the circadian amplitude of these genes, and led to an increase in the number of genes that responded to subsequent total sleep deprivation from 122 to 856. Genes affected by insufficient sleep were associated with circadian rhythms (PER1, PER2, PER3, CRY2, CLOCK, NR1D1, NR1D2, RORA, DEC1, CSNK1E), sleep homeostasis (IL6, STAT3, KCNV2, CAMK2D), oxidative stress (PRDX2, PRDX5), and metabolism (SLC2A3, SLC2A5, GHRL, ABCA1). Biological processes affected included chromatin modification, gene-expression regulation, macromolecular metabolism, and inflammatory, immune and stress responses. Thus, insufficient sleep affects the human blood transcriptome, disrupts its circadian regulation, and intensifies the effects of acute total sleep deprivation. The identified biological processes may be involved with the negative effects of sleep loss on health, and highlight the interrelatedness of sleep homeostasis, circadian rhythmicity, and metabolism.

  • Bucca G, Laing E, Mersinias V, Allenby N, Hurd D, Holdstock J, Brenner V, Harrison M, Smith CP. (2009) 'Development and application of versatile high density microarrays for genome-wide analysis of Streptomyces coelicolor: characterization of the HspR regulon'. BIOMED CENTRAL LTD GENOME BIOLOGY, 10 (1) Article number ARTN R5
  • Laing E, Sidhu K, Hubbard SJ. (2008) 'Predicted transcription factor binding sites as predictors of operons in Escherichia coli and Streptomyces coelicolor'. BIOMED CENTRAL LTD BMC GENOMICS, 9 Article number ARTN 79

Journal articles

  • Freire Martín I, Thomas CM, Laing E, AbuOun M, La Ragione RM, Woodward MJ. (2016) 'Curing vector for IncI1 plasmids and its use to provide evidence for a metabolic burden of IncI1 CTX-M-1 plasmid pIFM3791 on Klebsiella pneumoniae'. Journal of Medical Microbiology,
    [ Status: Accepted ]

    Abstract

    Using a sequence based approach we previously identified an IncI1 CTX-M-1 plasmid, pIFM3791, on a single pig farm in the UK that was harboured by K. pneumoniae, Escherichia coli and Salmonella enterica serotype 4,5,12,i:-. To test the hypothesis that the plasmid had spread rapidly into these differing host bacteria we wished to assess whether the plasmid conferred a fitness advantage. To do this an IncI1 curing vector was constructed and used to displace the IncI1 CTX-M-1 plasmids from K. pneumoniae strain B3791 and several other unrelated IncI1 harbouring strains indicating the potential wider application of the curing plasmid. The IncI1 CTX-M-1 plasmid was re-introduced by conjugation into the cured K. pneumoniae strain and also a naturally IncI1 plasmid free S. enterica serotype 4,5,12,i:-, S348/1. Original, cured and complemented strains were tested for metabolic competence using BiologTM technology and in competitive growth, association to mammalian cells and biofilm formation experiments. The plasmid-cured K. pneumoniae strain grew more rapidly than either the original plasmid-carrying strain or plasmid-complemented strains in competition experiments. Additionally, the plasmid-cured strain was significantly better at respiring with L-sorbose as a carbon source and putrescine, γ-amino-n-butyric acid, L-alanine, L-proline as a nitrogen sources. By contrast, no differences in phenotype were found when comparing plasmid harbouring and plasmid free S. enterica S348/11. In conclusion, the IncI1 curing vector successfully displaced multiple IncI plasmids. The IncI1 CTX-M1 plasmid conferred a growth disadvantage upon K. pneumoniae, possibly by imposing a metabolic burden the mechanism of which remains to be determined.

  • Matia-Gonzalez AM, Laing EE, Gerber AP. (2015) 'Conserved mRNA-binding proteomes in eukaryotic organisms'. NATURE PUBLISHING GROUP NATURE STRUCTURAL & MOLECULAR BIOLOGY, 22 (12), pp. 1027-1033.
  • Laing EE, Johnston JD, Möller-Levet CS, Bucca G, Smith CP, Dijk DJ, Archer SN. (2015) 'Exploiting human and mouse transcriptomic data: Identification of circadian genes and pathways influencing health'. BioEssays, 37 (5), pp. 544-556.
  • Świątek-Połatyńska MA, Bucca G, Laing E, Gubbens J, Titgemeyer F, Smith CP, Rigali S, van Wezel GP. (2015) 'Genome-wide analysis of in vivo binding of the master regulator DasR in Streptomyces coelicolor identifies novel non-canonical targets.'. PLoS One, United States: 10 (4)

    Abstract

    Streptomycetes produce a wealth of natural products, including over half of all known antibiotics. It was previously demonstrated that N-acetylglucosamine and secondary metabolism are closely entwined in streptomycetes. Here we show that DNA recognition by the N-acetylglucosamine-responsive regulator DasR is growth-phase dependent, and that DasR can bind to sites in the S. coelicolor genome that have no obvious resemblance to previously identified DasR-responsive elements. Thus, the regulon of DasR extends well beyond what was previously predicted and includes a large number of genes with functions far removed from N-acetylglucosamine metabolism, such as genes for small RNAs and DNA transposases. Conversely, the DasR regulon during vegetative growth largely correlates to the presence of canonical DasR-responsive elements. The changes in DasR binding in vivo following N-acetylglucosamine induction were studied in detail and a possible molecular mechanism by which the influence of DasR is extended is discussed. Discussion of DasR binding was further informed by a parallel transcriptome analysis of the respective cultures. Evidence is provided that DasR binds directly to the promoters of all genes encoding pathway-specific regulators of antibiotic production in S. coelicolor, thereby providing an exquisitely simple link between nutritional control and secondary metabolism.

  • Rahman T, Mahapatra M, Laing E, Jin Y. (2014) 'Evolutionary non-linear modelling for selecting vaccines against antigenically variable viruses.'. Bioinformatics, England: 31 (6), pp. 834-840.
  • Wagley S, Newcombe J, Laing E, Yusuf E, Sambles CM, Studholme DJ, La Ragione RM, Titball RW, Champion OL. (2014) 'Differences in carbon source utilisation distinguish Campylobacter jejuni from Campylobacter coli.'. BMC Microbiol, England: 14
  • Romero DA, Hasan AH, Lin YF, Kime L, Ruiz-Larrabeiti O, Urem M, Bucca G, Mamanova L, Laing EE, van Wezel GP, Smith CP, Kaberdin VR, McDowall KJ. (2014) 'A comparison of key aspects of gene regulation in Streptomyces coelicolor and Escherichia coli using nucleotide-resolution transcription maps produced in parallel by global and differential RNA sequencing.'. Mol Microbiol,

    Abstract

    Streptomyces coelicolor is a model for studying bacteria renowned as the foremost source of natural products used clinically. Post-genomic studies have revealed complex patterns of gene expression and links to growth, morphological development and individual genes. However, the underlying regulation remains largely obscure, but undoubtedly involves steps after transcription initiation. Here we identify sites involved in RNA processing and degradation as well as transcription within a nucleotide-resolution map of the transcriptional landscape. This was achieved by combining RNA-sequencing approaches suited to the analysis of GC-rich organisms. Escherichia coli was analysed in parallel to validate the methodology and allow comparison. Previously, sites of RNA processing and degradation had not been mapped on a transcriptome-wide scale for E. coli. Through examples, we show the value of our approach and data sets. This includes the identification of new layers of transcriptional complexity associated with several key regulators of secondary metabolism and morphological development in S. coelicolor and the identification of host-encoded leaderless mRNA and rRNA processing associated with the generation of specialized ribosomes in E. coli. New regulatory small RNAs were identified for both organisms. Overall the results illustrate the diversity in mechanisms used by different bacterial groups to facilitate and regulate gene expression.

  • Hasan S, van der Veen DR, Winsky-Sommerer R, Hogben A, Laing EE, Koentgen F, Dijk DJ, Archer SN. (2014) 'A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism.'. FASEB J,

    Abstract

    In humans, a primate-specific variable-number tandem-repeat (VNTR) polymorphism (4 or 5 repeats 54 nt in length) in the circadian gene PER3 is associated with differences in sleep timing and homeostatic responses to sleep loss. We investigated the effects of this polymorphism on circadian rhythmicity and sleep homeostasis by introducing the polymorphism into mice and assessing circadian and sleep parameters at baseline and during and after 12 h of sleep deprivation (SD). Microarray analysis was used to measure hypothalamic and cortical gene expression. Circadian behavior and sleep were normal at baseline. The response to SD of 2 electrophysiological markers of sleep homeostasis, electroencephalography (EEG) θ power during wakefulness and δ power during sleep, were greater in the Per3(5/5) mice. During recovery, the Per3(5/5) mice fully compensated for the SD-induced deficit in δ power, but the Per3(4/4) and wild-type mice did not. Sleep homeostasis-related transcripts (e.g., Homer1, Ptgs2, and Kcna2) were differentially expressed between the humanized mice, but circadian clock genes were not. These data are in accordance with the hypothesis derived from human data that the PER3 VNTR polymorphism modifies the sleep homeostatic response without significantly influencing circadian parameters.-Hasan, S., van der Veen, D. R., Winsky-Sommerer, R., Hogben, A., Laing, E. E., Koentgen, F., Dijk, D.-J., Archer, S. N. A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism.

  • Archer SN, Laing EE, Moeller-Levet CS, van der Veen DR, Bucca G, Lazar AS, Santhi N, Slak A, Kabiljo R, von Schantz M, Smith CP, Dijk D-J. (2014) 'Mistimed sleep disrupts circadian regulation of the human transcriptome'. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111 (6), pp. E682-E691.
  • Rico S, Santamaría RI, Yepes A, Rodríguez H, Laing E, Bucca G, Smith CP, Díaz M. (2014) 'Deciphering the regulon of Streptomyces coelicolor AbrC3, a positive response regulator of antibiotic production.'. Appl Environ Microbiol, United States: 80 (8), pp. 2417-2428.

    Abstract

    The atypical two-component system (TCS) AbrC1/C2/C3 (encoded by SCO4598, SCO4597, and SCO4596), comprising two histidine kinases (HKs) and a response regulator (RR), is crucial for antibiotic production in Streptomyces coelicolor and for morphological differentiation under certain nutritional conditions. In this study, we demonstrate that deletion of the RR-encoding gene, abrC3 (SCO4596), results in a dramatic decrease in actinorhodin (ACT) and undecylprodiginine (RED) production and delays morphological development. In contrast, the overexpression of abrC3 in the parent strain leads to a 33% increase in ACT production in liquid medium. Transcriptomic analysis and chromatin immunoprecipitation with microarray technology (ChIP-chip) analysis of the ΔabrC3 mutant and the parent strain revealed that AbrC3 directly controls ACT production by binding to the actII-ORF4 promoter region; this was independently verified by in vitro DNA-binding assays. This binding is dependent on the sequence 5'-GAASGSGRMS-3'. In contrast, the regulation of RED production is not due to direct binding of AbrC3 to either the redZ or redD promoter region. This study also revealed other members of the AbrC3 regulon: AbrC3 is a positive autoregulator which also binds to the promoter regions of SCO0736, bdtA (SCO3328), absR1 (SCO6992), and SCO6809. The direct targets share the 10-base consensus binding sequence and may be responsible for some of the phenotypes of the ΔabrC3 mutant. The identification of the AbrC3 regulon as part of the complex regulatory network governing antibiotic production widens our knowledge regarding TCS involvement in control of antibiotic synthesis and may contribute to the rational design of new hyperproducer host strains through genetic manipulation of such systems.

  • Archer SN, Laing EE, Möller-Levet CS, van der Veen DR, Bucca G, Lazar AS, Santhi N, Slak A, Kabiljo R, von Schantz M, Smith CP, Dijk DJ. (2014) 'Mistimed sleep disrupts circadian regulation of the human transcriptome.'. Proc Natl Acad Sci U S A,

    Abstract

    Circadian organization of the mammalian transcriptome is achieved by rhythmic recruitment of key modifiers of chromatin structure and transcriptional and translational processes. These rhythmic processes, together with posttranslational modification, constitute circadian oscillators in the brain and peripheral tissues, which drive rhythms in physiology and behavior, including the sleep-wake cycle. In humans, sleep is normally timed to occur during the biological night, when body temperature is low and melatonin is synthesized. Desynchrony of sleep-wake timing and other circadian rhythms, such as occurs in shift work and jet lag, is associated with disruption of rhythmicity in physiology and endocrinology. However, to what extent mistimed sleep affects the molecular regulators of circadian rhythmicity remains to be established. Here, we show that mistimed sleep leads to a reduction of rhythmic transcripts in the human blood transcriptome from 6.4% at baseline to 1.0% during forced desynchrony of sleep and centrally driven circadian rhythms. Transcripts affected are key regulators of gene expression, including those associated with chromatin modification (methylases and acetylases), transcription (RNA polymerase II), translation (ribosomal proteins, initiation, and elongation factors), temperature-regulated transcription (cold inducible RNA-binding proteins), and core clock genes including CLOCK and ARNTL (BMAL1). We also estimated the separate contribution of sleep and circadian rhythmicity and found that the sleep-wake cycle coordinates the timing of transcription and translation in particular. The data show that mistimed sleep affects molecular processes at the core of circadian rhythm generation and imply that appropriate timing of sleep contributes significantly to the overall temporal organization of the human transcriptome.

  • Möller-Levet CS, Archer SN, Bucca G, Laing EE, Slak A, Kabiljo R, Lo JC, Santhi N, von Schantz M, Smith CP, Dijk DJ. (2013) 'Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome.'. Proc Natl Acad Sci U S A, United States: 110 (12), pp. E1132-E1141.

    Abstract

    Insufficient sleep and circadian rhythm disruption are associated with negative health outcomes, including obesity, cardiovascular disease, and cognitive impairment, but the mechanisms involved remain largely unexplored. Twenty-six participants were exposed to 1 wk of insufficient sleep (sleep-restriction condition 5.70 h, SEM = 0.03 sleep per 24 h) and 1 wk of sufficient sleep (control condition 8.50 h sleep, SEM = 0.11). Immediately following each condition, 10 whole-blood RNA samples were collected from each participant, while controlling for the effects of light, activity, and food, during a period of total sleep deprivation. Transcriptome analysis revealed that 711 genes were up- or down-regulated by insufficient sleep. Insufficient sleep also reduced the number of genes with a circadian expression profile from 1,855 to 1,481, reduced the circadian amplitude of these genes, and led to an increase in the number of genes that responded to subsequent total sleep deprivation from 122 to 856. Genes affected by insufficient sleep were associated with circadian rhythms (PER1, PER2, PER3, CRY2, CLOCK, NR1D1, NR1D2, RORA, DEC1, CSNK1E), sleep homeostasis (IL6, STAT3, KCNV2, CAMK2D), oxidative stress (PRDX2, PRDX5), and metabolism (SLC2A3, SLC2A5, GHRL, ABCA1). Biological processes affected included chromatin modification, gene-expression regulation, macromolecular metabolism, and inflammatory, immune and stress responses. Thus, insufficient sleep affects the human blood transcriptome, disrupts its circadian regulation, and intensifies the effects of acute total sleep deprivation. The identified biological processes may be involved with the negative effects of sleep loss on health, and highlight the interrelatedness of sleep homeostasis, circadian rhythmicity, and metabolism.

  • Swiatek MA, Gubbens J, Bucca G, Song E, Yang YH, Laing E, Kim BG, Smith CP, van Wezel GP. (2013) 'The ROK-family regulator Rok7B7 pleiotropicaly affects xylose utilization, carbon catabolite repression and antibiotic production in Streptomyces coelicolor.'. American Society for Microbiology J Bacteriol, 195 (6), pp. 1236-1248.

    Abstract

    Members of the ROK family of proteins are mostly transcriptional regulators and kinases that generally relate to the control of primary metabolism, whereby its member glucose kinase acts as the central control protein in carbon control in Streptomyces. Here we show that deletion of SCO6008 (rok7B7) strongly affects carbon catabolite repression (CCR), growth and antibiotic production in Streptomyces coelicolor. Deletion of SCO7543 also affected antibiotic production, while no major changes were observed after deletion of the rok family genes SCO0794, SCO1060, SCO2846, SCO6566 or SCO6600. Global expression profiling of the rok7B7 mutant by proteomics and microarray analysis revealed strong up-regulation of the xylose transporter operon xylFGH, which lies immediately downstream of rok7B7, consistent with the improved growth and delayed development of the mutant on xylose. The enhanced CCR, which was especially obvious on rich or xylose-containing media, correlated with elevated expression of glucose kinase and of the glucose transporter GlcP. In liquid-grown cultures, expression of the biosynthetic enzymes for production of prodigionines (Red), siderophores and calcium dependent antibiotic (Cda) was enhanced in the mutant, and overproduction of Red was corroborated by MALDI-ToF analysis. These data present Rok7B7 as a pleiotropic regulator of growth, CCR and antibiotic production in Streptomyces.

  • Salerno P, Persson J, Bucca G, Laing E, Ausmees N, Smith CP, Flärdh K. (2013) 'Identification of new developmentally regulated genes involved in Streptomyces coelicolor sporulation.'. BMC Microbiol, England: 13

    Abstract

    The sporulation of aerial hyphae of Streptomyces coelicolor is a complex developmental process. Only a limited number of the genes involved in this intriguing morphological differentiation programme are known, including some key regulatory genes. The aim of this study was to expand our knowledge of the gene repertoire involved in S. coelicolor sporulation.

  • Allenby NE, Laing E, Bucca G, Kierzek AM, Smith CP. (2012) 'Diverse control of metabolism and other cellular processes in Streptomyces coelicolor by the PhoP transcription factor: genome-wide identification of in vivo targets.'. Oxford University Press Nucleic Acids Res,

    Abstract

    Streptomycetes sense and respond to the stress of phosphate starvation via the two-component PhoR-PhoP signal transduction system. To identify the in vivo targets of PhoP we have undertaken a chromatin-immunoprecipitation-on-microarray analysis of wild-type and phoP mutant cultures and, in parallel, have quantified their transcriptomes. Most (ca. 80%) of the previously in vitro characterized PhoP targets were identified in this study among several hundred other putative novel PhoP targets. In addition to activating genes for phosphate scavenging systems PhoP was shown to target two gene clusters for cell wall/extracellular polymer biosynthesis. Furthermore PhoP was found to repress an unprecedented range of pathways upon entering phosphate limitation including nitrogen assimilation, oxidative phosphorylation, nucleotide biosynthesis and glycogen catabolism. Moreover, PhoP was shown to target many key genes involved in antibiotic production and morphological differentiation, including afsS, atrA, bldA, bldC, bldD, bldK, bldM, cdaR, cdgA, cdgB and scbR-scbA. Intriguingly, in the PhoP-dependent cpk polyketide gene cluster, PhoP accumulates substantially at three specific sites within the giant polyketide synthase-encoding genes. This study suggests that, following phosphate limitation, Streptomyces coelicolor PhoP functions as a 'master' regulator, suppressing central metabolism, secondary metabolism and developmental pathways until sufficient phosphate is salvaged to support further growth and, ultimately, morphological development.

  • Bonde BK, Beste DJV, Laing E, Kierzek AM, McFadden J. (2011) 'Differential Producibility Analysis (DPA) of Transcriptomic Data with Metabolic Networks: Deconstructing the Metabolic Response of M. tuberculosis'. PUBLIC LIBRARY SCIENCE PLOS COMPUTATIONAL BIOLOGY, 7 (6) Article number ARTN e1002060
  • Lewis RA, Shahi SK, Laing E, Bucca G, Efthimiou G, Bushell M, Smith CP. (2011) 'Genome-wide transcriptomic analysis of the response to nitrogen limitation in Streptomyces coelicolor A3(2).'. BMC Res Notes, England: 4
  • Laing E, Smith CP. (2010) 'RankProdIt: A web-interactive Rank Products analysis tool.'. BMC Res Notes, England: 3
  • Lewis RA, Laing E, Allenby N, Bucca G, Brenner V, Harrison M, Kierzek AM, Smith CP. (2010) 'Metabolic and evolutionary insights into the closely-related species Streptomyces coelicolor and Streptomyces lividans deduced from high-resolution comparative genomic hybridization'. BIOMED CENTRAL LTD BMC GENOMICS, 11 Article number ARTN 682
  • Salerno P, Larsson J, Bucca G, Laing E, Smith CP, Flardh K. (2009) 'One of the Two Genes Encoding Nucleoid-Associated HU Proteins in Streptomyces coelicolor Is Developmentally Regulated and Specifically Involved in Spore Maturation'. AMER SOC MICROBIOLOGY J BACTERIOL, 191 (21), pp. 6489-6500.
  • Sooriakumaran P, Macanas-Pirard P, Bucca G, Henderson A, Langley SE, Laing RW, Smith CP, Laing EE, Coley HM. (2009) 'A gene expression profiling approach assessing celecoxib in a randomized controlled trial in prostate cancer.'. International Institute of Anticancer Research (IIAR) Cancer Genomics Proteomics, Greece: 6 (2), pp. 93-99.

    Abstract

    We performed a pilot study, looking at the COX-2 inhibitor celecoxib, on newly diagnosed prostate cancer patients in the neo-adjuvant setting using DNA microarray analysis.

  • Bucca G, Laing E, Mersinias V, Allenby N, Hurd D, Holdstock J, Brenner V, Harrison M, Smith CP. (2009) 'Development and application of versatile high density microarrays for genome-wide analysis of Streptomyces coelicolor: characterization of the HspR regulon'. BIOMED CENTRAL LTD GENOME BIOLOGY, 10 (1) Article number ARTN R5
  • Laing E, Sidhu K, Hubbard SJ. (2008) 'Predicted transcription factor binding sites as predictors of operons in Escherichia coli and Streptomyces coelicolor'. BIOMED CENTRAL LTD BMC GENOMICS, 9 Article number ARTN 79
  • Hesketh A, Bucca G, Laing E, Flett F, Hotchkiss G, Smith CP, Chater KF. (2007) 'New pleiotropic effects of eliminating a rare tRNA from Streptomyces coelicolor, revealed by combined proteomic and transcriptomic analysis of liquid cultures'. BIOMED CENTRAL LTD BMC GENOMICS, 8 Article number ARTN 261
  • Beste DJV, Laing E, Bonde B, Avignone-Rossa C, Bushell ME, McFadden JJ. (2007) 'Transcriptomic analysis identifies growth rate modulation as a component of the adaptation of mycobacteria to survival inside the macrophage'. AMER SOC MICROBIOLOGY JOURNAL OF BACTERIOLOGY, 189 (11), pp. 3969-3976.
  • Noens EE, Mersinias V, Willemse J, Traag BA, Laing E, Chater KF, Smith CP, Koerten HK, van Wezel GP. (2007) 'Loss of the controlled localization of growth stage-specific cell-wall synthesis pleiotropically affects developmental gene expression in an ssgA mutant of Streptomyces coelicolor'. BLACKWELL PUBLISHING MOLECULAR MICROBIOLOGY, 64 (5), pp. 1244-1259.
  • Tellez JO, Dobrzynski H, Greener ID, Graham GM, Laing E, Honjo H, Hubbard SJ, Boyett MR, Billeter R. (2006) 'Differential expression of ion channel transcripts in atrial muscle and sinoatrial node in rabbit'. LIPPINCOTT WILLIAMS & WILKINS CIRCULATION RESEARCH, 99 (12), pp. 1384-1393.
  • Laing E, Mersinias V, Smith CP, Hubbard SJ. (2006) 'Analysis of gene expression in operons of Streptomyces coelicolor'. BIOMED CENTRAL LTD GENOME BIOLOGY, 7 (6) Article number ARTN R46

Conference papers

  • Archer SN, Laing EE, Moller-Levet CS, van der Veen DR, Bucca G, Lazar AS, Lo JCY, Santhi N, Slak A, Kabiljo R, von Schantz M, Smith CP, Dijk DJ. (2014) 'Mistimed sleep disrupts the circadian regulation of the human transcriptome'. WILEY-BLACKWELL JOURNAL OF SLEEP RESEARCH, Tallinn, ESTONIA: 22nd Congress of the European-Sleep-Research-Society 23, pp. 15-15.
  • Thomas SA, Jin Y, Laing E, Smith CP. (2013) 'Reconstructing regulatory networks in Streptomyces using evolutionary algorithms'. 2013 13th UK Workshop on Computational Intelligence, UKCI 2013, , pp. 24-30.
  • Lordan J, Karanjia N, Bucca G, Laing E, Smith C. (2010) 'Prospective analysis of the gene expression signature of peri-metastasis 'halo' tissue following neo-adjuvant chemotherapy-induced tumour reduction of colorectal liver metastasis'. WILEY-BLACKWELL BRITISH JOURNAL OF SURGERY, Liverpool, ENGLAND: Electronic Poster of Distinction in Association-of-Surgeons-of-Great-Britain-and-Ireland-International-Surgical-Congress 97, pp. 61-62.

Book chapters

  • Thomas SA, jin Y, Laing E, Smith CP. (2016) 'Modeling Dynamic Gene Expression in Streptomyces Coelicolor: Comparing Single and Multi-Objective Setups'. in Iba H, Noman N (eds.) Evolutionary Computation in Gene Regulatory Network Research John Wiley & Sons Article number 7

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