Imperial College London

DrMichaelJones

Faculty of MedicineDepartment of Infectious Disease

Reader in Molecular Medicine
 
 
 
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Contact

 

+44 (0)20 3313 1643m.d.jones

 
 
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Location

 

8N23Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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42 results found

Mollet IG, Patel D, Govani FS, Giess A, Paschalaki K, Periyasamy M, Lidington EC, Mason JC, Jones MD, Game L, Ali S, Shovlin CLet al., 2016, Low Dose Iron Treatments Induce a DNA Damage Response in Human Endothelial Cells within Minutes, PLOS One, Vol: 11, ISSN: 1932-6203

BackgroundSpontaneous reports from patients able to report vascular sequelae in real time, and recognitionthat serum non transferrin bound iron may reach or exceed 10μmol/L in the bloodstream after iron tablets or infusions, led us to hypothesize that conventional iron treatmentsmay provoke acute vascular injury. This prompted us to examine whether a phenotypecould be observed in normal human endothelial cells treated with low dose iron.MethodologyConfluent primary human endothelial cells (EC) were treated with filter-sterilized iron (II) citrateor fresh media for RNA sequencing and validation studies. RNA transcript profiles wereevaluated using directional RNA sequencing with no pre-specification of target sequences.Alignments were counted for exons and junctions of the gene strand only, blinded to treatmenttypes.Principal FindingsRapid changes in RNA transcript profiles were observed in endothelial cells treated with10μmol/L iron (II) citrate, compared to media-treated cells. Clustering for Gene Ontology(GO) performed on all differentially expressed genes revealed significant differences in biologicalprocess terms between iron and media-treated EC, whereas 10 sets of an equivalentnumber of randomly selected genes from the respective EC gene datasets showed no significantdifferences in any GO terms. After 1 hour, differentially expressed genes clusteredto vesicle mediated transport, protein catabolism, and cell cycle (Benjamini p = 0.0016,0.0024 and 0.0032 respectively), and by 6 hours, to cellular response to DNA damage stimulusmost significantly through DNA repair genes FANCG, BLM, and H2AFX. Comet assays demonstrated that 10μM iron treatment elicited DNA damage within 1 hour. This wasaccompanied by a brisk DNA damage response pulse, as ascertained by the developmentof DNA damage response (DDR) foci, and p53 stabilization.SignificanceThese data suggest that low dose iron treatments are sufficient to modify the vascular endothelium,and induce a DNA damage

Journal article

Turner CE, Lamagni T, Holden MT, David S, Jones M, Game L, Efstratiou A, Sriskandan Set al., 2015, Turner et al. Reply to “Emergence of the Same Successful Clade among Distinct Populations of emm89 Streptococcus pyogenes in Multiple Geographic Regions”, mBio, Vol: 6, ISSN: 2161-2129

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

Shovlin CL, Govani FS, Mollet IG, Thomas E, Jones MD, Giess A, Game Let al., 2014, VERY HIGH QUALITY NEXT-GENERATION DNA SEQUENCING DATA FROM HUMAN GENOMIC DNA SAMPLES STORED, AND INTERMITTENTLY DEFROSTED OVER TWO DECADES, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A83-A83, ISSN: 0040-6376

Conference paper

Shovlin CL, Mollet IG, Giess A, Thomas E, Jones MD, Game L, Govani FSet al., 2014, MOLECULAR COMPLEXITIES IDENTIFIED THROUGH TARGETED GENOMIC SEQUENCING OF THE HHT3 LOCUS ON CHROMOSOME 5, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A84-A85, ISSN: 0040-6376

Conference paper

Shovlin CL, Patel D, Govani FS, Giess A, Jones MD, Game L, Mollet IGet al., 2014, DIRECTIONAL NEXT GENERATION WHOLE TRANSCRIPTOME SEQUENCING OF PRIMARY HUMAN PULMONARY MICROVASCULAR ENDOTHELIAL CELLS, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A83-A84, ISSN: 0040-6376

Conference paper

Govani FS, Giess A, Mollet IG, Begbie ME, Jones MD, Game L, Shovlin CLet al., 2013, Directional Next-Generation RNA Sequencing and Examination of Premature Termination Codon Mutations in Endoglin/Hereditary Haemorrhagic Telangiectasia, Molecular Syndromology, Vol: 4, Pages: 184-196, ISSN: 1661-8777

Hereditary haemorrhagic telangiectasia (HHT) is a disease characterised by abnormal vascular structures, and most commonly caused by mutations in ENG, ACVRL1 or SMAD4 encoding endothelial cell-expressed proteins involved in TGF- superfamily signalling. The majority of mutations reported on the HHT mutation database are predicted to lead to stop codons, either due to frameshifts or direct nonsense substitutions. The proportion is higher for ENG (67%) and SMAD4 (65%) than for ACVRL1 (42%), p<0.0001). Here, by focussing on ENG, we report why conventional views of these mutations may need to be revised. Of the 111 stop codon-generating ENG mutations, on ExPASy translation, all except one was a premature termination codon, sited at least 50-55bp upstream of the final exon-exon boundary of the main endoglin isoform, L-endoglin. This strongly suggests that the mutated RNA species will undergo nonsense mediated decay. We provide new in vitro expression data to support dominant negative activity of stable truncated endoglin proteins but suggest these will not generate HHT: The single natural stop codon mutation in L-endoglin (sited within 50-55nucleotides of the final exon-exon boundary) is unlikely to generate functional protein since it replaces the entire transmembrane domain, as would eight further natural stop codon mutations, if the minor S-endoglin isoform were implicated in HHT pathogeneses. Finally, next generation RNA sequencing data of seven different RNA libraries from primary human endothelial cells demonstrate that multiple intronic regions of ENG are transcribed. The potential consequences of heterozygous deletions or duplications of such regions are discussed. These data support the haploinsufficiency model for HHT pathogenesis; explain why final exon mutations have not been detected to date in HHT; emphasise the potential need for functional examination of non PTC-generating mutations; and lead to proposals for an alternate stratification system of

Journal article

Buluwela L, Kamalati T, Photiou A, Heathcote DA, Jones MD, Ali Set al., 2010, A Simple Laboratory Practical to Illustrate RNA Mediated Gene Interference Using Drosophila Cell Culture, BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION, Vol: 38, Pages: 393-399, ISSN: 1470-8175

Journal article

O'Kane CM, Elkington PT, Jones MD, Caviedes L, Tovar M, Gilman RH, Stamp G, Friedland JSet al., 2010, STAT3, p38 MAPK, and NF-kappa B Drive Unopposed Monocyte-Dependent Fibroblast MMP-1 Secretion in Tuberculosis, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol: 43, Pages: 465-474, ISSN: 1044-1549

Journal article

Turner CE, Kurupati P, Jones MD, Edwards RJ, Sriskandan Set al., 2009, Emerging role of the interleukin-8 cleaving enzyme SpyCEP in clinical Streptococcus pyogenes (The Journal of Infectious Diseases (2009) 200 (555-563)), Journal of Infectious Diseases, Vol: 200, ISSN: 0022-1899

Journal article

Turner CE, Kurupati P, Jones MD, Edwards RJ, Sriskandan Set al., 2009, Emerging Role of the Interleukin-8 Cleaving Enzyme SpyCEP in Clinical Streptococcus pyogenes Infection, JOURNAL OF INFECTIOUS DISEASES, Vol: 200, Pages: 555-563, ISSN: 0022-1899

Journal article

O'Kane CM, Jones MD, Elkington PTG, Friedland JSet al., 2005, Monocyte fibroblast networks drive matrix degradation in tuberculosis, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: II44-II44, ISSN: 0040-6376

Conference paper

Calcagno AM, Bignell E, Rogers TR, Jones MD, Muhlschlegel FA, Haynes Ket al., 2005, Candida glabrata Ste11 is involved in adaptation to hypertonic stress, maintenance of wild-type levels of filamentation and plays a role in virulence, MEDICAL MYCOLOGY, Vol: 43, Pages: 355-364, ISSN: 1369-3786

Journal article

Mellor N, Themis M, Selden C, Jones M, Hodgson HJFet al., 2004, Characteristics of murine histidinaemia and its potential for genetic manipulation, Liver International, Vol: 24, Pages: 354-360, ISSN: 1478-3223

Journal article

Kamran M, Calcagno AM, Findon H, Bignell E, Jones MD, Warn P, Hopkins P, Denning DW, Butler G, Rogers T, Muhlschlegel FA, Haynes Ket al., 2004, Inactivation of transcription factor gene ACE2 in the fungal pathogen Candida glabrata results in hypervirulence, EUKARYOTIC CELL, Vol: 3, Pages: 546-552, ISSN: 1535-9778

Journal article

Calcagno AM, Bignell E, Warn P, Jones MD, Denning DW, Muhlschlegel FA, Rogers TR, Haynes Ket al., 2003, Candida glabrata STE12 is required for wild-type levels of virulence and nitrogen starvation induced filamentation, MOLECULAR MICROBIOLOGY, Vol: 50, Pages: 1309-1318, ISSN: 0950-382X

Journal article

Shaunak S, Thornton M, Teo I, Chandler B, Jones M, Steel Set al., 2003, Optimisation of the degree of sulfation of a polymer based construct to block the entry of HIV-1 into cells, JOURNAL OF DRUG TARGETING, Vol: 11, Pages: 443-448, ISSN: 1061-186X

Journal article

Xue SA, Jones MD, Lu QL, Middeldorp JM, Griffin BEet al., 2003, Genetic diversity: Frameshift mechanisms alter coding of a gene (Epstein-Barr virus LF3 gene) that contains multiple 102-base-pair direct sequence repeats, MOLECULAR AND CELLULAR BIOLOGY, Vol: 23, Pages: 2192-2201, ISSN: 0270-7306

Journal article

Xue SA, Lu QL, Poulsom R, Karran L, Jones MD, Griffin BEet al., 2000, Expression of two related viral early genes in Epstein-Barr virus-associated tumors, JOURNAL OF VIROLOGY, Vol: 74, Pages: 2793-2803, ISSN: 0022-538X

Journal article

Elliott J, Jones MD, Griffin BE, Krauzewicz Net al., 1998, Regulation of cytoskeletal association by a basic amino acid motif in polyoma virus middle T antigen, ONCOGENE, Vol: 17, Pages: 1797-1806, ISSN: 0950-9232

Journal article

Warrens AN, Jones MD, Lechler RI, 1997, Splicing by overlap extension by PCR using asymmetric amplification: An improved technique for the generation of hybrid proteins of immunological interest, GENE, Vol: 186, Pages: 29-35, ISSN: 0378-1119

Journal article

Selden AC, Mellor NM, Jones MD, Pignatelli M, Hodgson HJFet al., 1996, Autocrine stimulation of an immortal non-tumorous human liver epithelial cell line by transfected hepatocyte growth factor alters motility and slows growth., GASTROENTEROLOGY, Vol: 110, Pages: A1318-A1318, ISSN: 0016-5085

Journal article

HENSEL M, SHEA JE, GLEESON C, JONES MD, DALTON E, HOLDEN DWet al., 1995, SIMULTANEOUS IDENTIFICATION OF BACTERIAL VIRULENCE GENES BY NEGATIVE SELECTION, SCIENCE, Vol: 269, Pages: 400-403, ISSN: 0036-8075

Journal article

WEBB JC, PATEL DD, JONES MD, KNIGHT BL, SOUTAR AKet al., 1994, CHARACTERIZATION AND TISSUE-SPECIFIC EXPRESSION OF THE HUMAN VERY-LOW-DENSITY LIPOPROTEIN (VLDL) RECEPTOR MESSENGER-RNA, HUMAN MOLECULAR GENETICS, Vol: 3, Pages: 531-537, ISSN: 0964-6906

Journal article

JONES MD, TEO IA, 1993, IDENTIFICATION AND ANALYSIS OF THE TRANSPORT CAPSID ASSEMBLY PROTEIN (TP CAP) GENE OF HUMAN HERPESVIRUS-6 (HHV6), VIROLOGY, Vol: 197, Pages: 449-454, ISSN: 0042-6822

Journal article

JONES MD, 1993, REVERSE TRANSCRIPTION OF MESSENGER-RNA BY THERMUS-AQUATICUS DNA-POLYMERASE FOLLOWED BY POLYMERASE CHAIN-REACTION AMPLIFICATION, METHODS IN ENZYMOLOGY, Vol: 218, Pages: 413-419, ISSN: 0076-6879

Journal article

TEO IA, GRIFFIN BE, JONES MD, 1991, CHARACTERIZATION OF THE DNA-POLYMERASE GENE OF HUMAN HERPESVIRUS-6, JOURNAL OF VIROLOGY, Vol: 65, Pages: 4670-4680, ISSN: 0022-538X

Journal article

Griffin BE, Teo I, Jones MD, 1991, New herpesviruses and their relevance for man., Curr Biol, Vol: 1, Pages: 182-184, ISSN: 0960-9822

Journal article

MARTIN MED, THOMSON BJ, HONESS RW, CRAXTON MA, GOMPELS UA, LIU MY, LITTLER E, ARRAND JR, TEO I, JONES MDet al., 1991, THE GENOME OF HUMAN HERPESVIRUS-6 - MAPS OF UNIT-LENGTH AND CONCATEMERIC GENOMES FOR 9 RESTRICTION ENDONUCLEASES, JOURNAL OF GENERAL VIROLOGY, Vol: 72, Pages: 157-168, ISSN: 0022-1317

Journal article

Martin ME, Thomson BJ, Honess RW, Craxton MA, Gompels UA, Liu MY, Littler E, Arrand JR, Teo I, Jones MDet al., 1991, The genome of human herpesvirus 6: maps of unit-length and concatemeric genomes for nine restriction endonucleases., J Gen Virol, Vol: 72 ( Pt 1), Pages: 157-168, ISSN: 0022-1317

More than 50 fragments resulting from complete digestion of the DNA of human herpesvirus 6 (HHV-6, strain U1102) with BamHI, EcoRI, HindIII, KpnI, NruI, SalI or SmaI have been isolated as clones in M13, plasmid, cosmid and lambda vectors. Using these clones, maps have been constructed for the fragments produced by nine restriction enzymes from unit-length virus genomes and from their concatemeric precursors. The unit-length genome is a linear, double-stranded molecule of 161.5 kbp composed of a central segment of a largely unique sequence of 141 kbp (U) with a sequence of 10 kbp duplicated in the same orientation at both 'left' and 'right' genomic termini (i.e. 'left' and 'right' copies of the direct repeat; DRL and DRR). Adopting as standard an orientation in which the major capsid protein gene is 'left' of the gene for alkaline exonuclease, then the 'right' genome termini and DRL. U junctions occur close to or within repetitive (GGGTTA)n sequences. Repetitions of short sequence motifs are present in at least two other regions of the genome. One of these regions consists of a simple repeat (TC/G) of approximately 1.5 kbp in length and is unstable as clones in bacterial vectors. The second region is stably maintained in such vectors and consists of a tandem array of at least 25 copies of a 110 bp sequence containing a single KpnI site. Comparisons of fragments arising from unit-length DNA with those from virus DNA from the nuclei of infected cells have shown that the concatemeric junctions in intracellular DNA contain head-to-tail dimers of the terminal duplications (i.e. ...U1.DRR1.DRL2.U2...). The gross structure established here for the genome from the U1102 isolate of HHV-6 resembles closely that suggested by Pellett and his colleagues for the Z29 isolate and differs from that of the five previously characterized human herpesviruses. This structure of HHV-6 DNA bears a superficial resemblance to that proposed for DNA from channel catfish virus and equine cytomeg

Journal article

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