Open to any in silico based research but particular areas of interest to me are:
Development of novel algorithms for high-throughput –omics (transcriptomics, translatomics, proteomics etc) analysis.
Development of bioinformatic tools for data interpretation
The integration of multi-omic large scale data sets
£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’. CA 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.
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).
Gareth Thomas (Principal supervisor, collaboration with Dr. Claudio Avignone-Rossa and Symbio Ltd.): The development of a microbial community for increasing wheat crop yield. Funded by BBSRC iCASE studentship.
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).
BMS2036 Molecular Biology and Genetics 2
BMS3072 Systems Biology : Genomes in Action
MSc Medical Microbiology
MSc Veterinary Microbiology
Applied Systems Biology CPD modules
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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Assembly date: Wed May 25 23:18:31 BST 2016
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