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Impact

Glasgow Polyomics has catalysed the wide spread use of all of the omics based research strands into biomedical and biological sciences across the University of Glasgow and beyond. Advances in our ability to collect huge datasets relating to all of the fundamental biochemical components of life is revolutionising how the biomedical sciences impact on all that we do. Below are a few examples of where our impact is being made.

We have completed over 1000 projects and we have a proven track record of innovation that allows us to deliver world-class research to academic institutions and industry on a range of diverse organisms, samples and projects. At Glasgow Polyomics our expertise has been utilised in clinical projects, industrial biotechnology, drug discovery and biomarker identification, ancient DNA from preserved samples. We have even analysed meteorites!

Glasgow Polyomics was featured in the BBC documentary with Dr Michael Mosley The Wonderful World of Blood in which samples of blood were analysed by mass spectrometry after eating different types of food.

Research Case Studies

Drug ResistanceClinicalArtsMethodsBiomarker

Drug Resistance and Mode of Action

Amphotericin B has emerged as the therapy of choice for use against leishmaniasis, a parasitic disease found in tropical regions. Glasgow Polyomics carried out liquid chromatography mass spectrometry and genome sequencing were used to understand the mechanisms of drug resistance by comparing wild type (WT) and lab-derived drug resistant lines. Changes in metabolites putatively identified the sterol metabolic pathway later confirmed through a targeted approach.

Diagram illustrating the metabolite peaks at different retention times, comparing between wild type and mutant parasites

The biggest difference was observed in ergosterol. Whole genome sequencing was carried out from wild type and resistant cell lines, specifically looking for genetic alteration in genes relating to the sterol metabolic pathway. A non-synonymous mutation was found in the gene encoding 14-demethylase.

Example Publications

Pountain et al. Genomic instability at the locus of sterol C24-methyltransferase promotes amphotericin B resistance in Leishmania parasites. DOI: 10.1371/journal.pntd.0007052

Mwenechanya et al. Sterol 14alpha-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana. DOI: 10.1371/journal.pntd.0005649

Clinical Studies

Glasgow Polyomics carried out a small scale study looking at changes in metabolites over time in an effort to reduce variability and produce meaningful data. For this proof-of-concept study, we worked with 7 trained cyclists, taking samples every 15 minutes. A comparison of two analysis methods was then used.

Diagram of a heatmap illustrating the levels of metabolites over the period of the study

Linear models were used to plot the changes in metabolites across the time-course and clear changes in metabolism identified across time, including the discovery of novel metabolites associated with post-fatigue recovery.

Example Publications

Blackburn et al. Running on empty: a metabolomics approach to investigating changing energy metabolism during fasted exercise and rest. DOI: 10.3390/metabo10100399

Rodgers et al. The rheumatoid synovial environment alters fatty acid metabolism in human monocytes and enhances CCL20 secretion. DOI: 10.1093/rheumatology/kez378

Arts and Humanities

Glasgow Polyomics is experienced in analysing historic samples or museum artefacts. For example, we sequenced DNA from historic lung samples in Hunter’s collection at the University of Glasgow which might have included tuberculosis bacteria. Investigations into the evolution of the Tuberculosis genome over several hundred years can help our understanding of Tuberculosis' re-emergence as a public health problem.

Image showing ink on paper

Mass spectrometry-based to analyse the composition of ink and paper used on contested works of Robert Burns and used to distinguish forged Burns documents. We have also worked with Computing Scientists to apply word-window machine-learning based clustering methods to a number of poems. A truly interdisciplinary project!

Publication

Newton et al. Minimally-destructive atmospheric ionisation mass spectrometry authenticates authorship of historical manuscripts. DOI: 10.1038/s41598-018-28810-2

Methods and Platform Development

At Glasgow Poyomics we work on a range of informatics and technical methods development projects in conjuction with researchers.

Example Publications

Nui et al. R package for statistical inference in dynamical systems using kernel based gradient matching: KGode. DOI: 10.1007/s00180-020-01014-x

Wandy et al. Ms2lda.org: web-based topic modelling for substructure discovery in mass spectrometry. DOI: 10.1093/bioinformatics/btx582

Gloaguen et al. PiMP my metabolome: An integrated, web-based tool for LC-MS metabolomics data. DOI: 10.1093/bioinformatics/btx499

Recknagel et al. Double-digest RAD sequencing using Ion Proton semiconductor platform (ddRADseq-ion) with nonmodel organisms. DOI: 10.1111/1755-0998.12406

LC-MS approach for Biomarker Discovery in Stroke

Glasgow Polyomics collaborated with Prof Jesse Dawson helped identify biomarkers in patients with suspected stroke and transient ischaemic attack (TIA). These results enhanced the understanding of stroke pathophysiology and distinguish from TIAs from other diagnoses. An initial study showed that there was little of significance found in serum, however clear differences were noted in urine. This was transferred to a large clinical cohort of over urine 500 samples. From this a variety of markers were identified that could contribute to statistical models predictive of stroke. Of huge significance was the identification of a metabolite (X) that was found almost exclusively in patients but not controls.

Graph showing the changes in metabolite levels between stroke patients and healthy controls

These studies have included the clinical environment in which the test will be used (using mimics as controls), and we have identified the clinical scenario in which biomarker levels differ most between cases and mimic. Its levels remain elevated for a prolonged window (1 week at least) leaving room for optimizing the window of its detection. The metabolite is not consistent with any metabolite in the human metabolome database, demonstrating the advantage of taking an untargeted metabolomics approach.

Example Publications

Daly et al. Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation. DOI: 10.3390/metabo10060241

Pesko et al. Post-mortomics: the potential of untargeted metabolomics to highlight markers for time since death. DOI: 10.1089/omi.2020.0084

Industrial Biotechnology Case Studies

Industry 1Industry 2Industry 3

CalaChem is a Scottish company based in Grangemouth specialising in contract manufacturing in agrochemical, pharmaceutical and chemical industries. One area of interest is the treatment of aqueous waste and the microbiological and biochemical environment in waste treatment tanks. Glasgow Polyomics analysed the bacterial diversity in the treatment tanks over time as well as the biochemistry of the waste. We were able to identify ways in which process efficiency may be improved, potentially providing significant value to the company.

CelluComp has developed a unique nano-cellulose-based fibre for use a wide variety of applications. A long-term partnership between CelluComp and Glasgow Polyomics has seen successful applications for a FoodWasteNet Business Interaction Voucher (BIV) and FoodWasteNet Proof of Concept (PoC) grant to valorise CelluComp’s secondary products.

Using the PoC funding, Glasgow Polyomics provided a biochemical analysis of CelluComp’s by-product streams. This was able to support CelluComp’s commercial goals, while providing valuable biochemical information about their waste streams.

Celtic Renewables produce biobased butanol, acetone, ethanol and high-grade animal feed using the residues (draff and pot ale) from the whisky industry. Glasgow Polyomics and Celtic Renewables were awarded an Impact Accelerator grant in 2017 from IBioIC to analyse the biochemistry of solvent production using metabolomics with the aim of improving fermentation success.

Several sample sets have already been analysed at Glasgow Polyomics’s state of the art facilities and the information garnered has been valuable to informing Celtic Renewables’s processes.

Selected Publications

    2021
  • Rossitto G et al. High sodium intake, glomerular hyperfiltration, and protein catabolism in patients with essential hypertension. DOI: 10.1093/cvr/cvaa205
  • Chung J et al. Rare Missense Functional Variants at COL4A1 and COL4A2 in Sporadic Intracerebral Hemorrhage. DOI: 10.1212/WNL.0000000000012227
  • Hodgkinson T et al. The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells. DOI: 10.1126/sciadv.abb7921
  • 2020
  • Savino AM et al. Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment is dependent on Stearoyl CoA desaturase. DOI: 10.1038/s43018-020-00115-2
  • McIntyre CL et al. beta2 Integrins differentially regulate gammadelta T cell subset thymic development and peripheral maintenance. DOI: 10.1073/pnas.1921930117
  • Orapiriyakul W et al. Nanovibrational Stimulation of Mesenchymal Stem Cells Induces Therapeutic Reactive Oxygen Species and Inflammation for Three-Dimensional Bone Tissue Engineering. DOI: 10.1021/acsnano.0c03130
  • 2019
  • Briggs E et al. Trypanosoma brucei ribonuclease H2A is an essential R-loop processing enzyme whose loss causes DNA damage during transcription initiation and antigenic variation. DOI: 10.1093/nar/gkz644
  • Wiejak J et al. Genome-Wide Mapping Defines a Role for C/EBPbeta and c-Jun in Non-Canonical Cyclic AMP Signalling. DOI: 10.3390/cells8101253
  • Keuss MJ et al. Unanchored tri-NEDD8 inhibits PARP-1 to protect from oxidative stress-induced cell death. DOI: 10.15252/embj.2018100024
  • 2018
  • Connolly JP et al. Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion. DOI: 10.1038/s41467-018-06701-4
  • Perrella G et al. ZINC-FINGER interactions mediate transcriptional regulation of hypocotyl growth in Arabidopsis. DOI: 10.1073/pnas.1718099115
  • Briggs E et al. Genome-wide mapping reveals conserved and diverged R-loop activities in the unusual genetic landscape of the African trypanosome genome. DOI: 10.1093/nar/gky928
  • 2017
  • Tsimbouri PM et al. Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor. DOI: 10.1038/s41551-017-0127-4
  • Mwenechanya R et al. Sterol 14alpha-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana. DOI: 10.1371/journal.pntd.0005649
  • Alakpa EV et al. Nacre Topography Produces Higher Crystallinity in Bone than Chemically Induced Osteogenesis. DOI: 10.1021/acsnano.7b01044
  • 2016
  • Vincent IM et al. Metabolomics Identifies Multiple Candidate Biomarkers to Diagnose and Stage Human African Trypanosomiasis. DOI: 10.1371/journal.pntd.0005140
  • Vincent IM et al. Untargeted Metabolomics To Ascertain Antibiotic Modes of Action. DOI: 10.1128/AAC.02109-15
  • Grewal JS et al. PNT1 is a C11 Cysteine Peptidase Essential for Replication of the Trypanosome Kinetoplast. DOI: 10.1074/jbc.M116.714972
  • 2015
  • Baker N et al. Vacuolar ATPase depletion affects mitochondrial ATPase function, kinetoplast dependency, and drug sensitivity in trypanosomes. DOI: 10.1073/pnas.1505411112
  • Zoccarato A et al. Cardiac Hypertrophy Is Inhibited by a Local Pool of cAMP Regulated by Phosphodiesterase 2. DOI: 10.1161/CIRCRESAHA.114.305892
  • Shameer S et al. TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei. DOI: 10.1093/nar/gku944
  • 2014
  • Huser CA et al. Insertional mutagenesis and deep profiling reveals gene hierarchies and a Myc/p53-dependent bottleneck in lymphomagenesis. DOI: 10.1371/journal.pgen.1004167
  • Rankin NJ et al. The emergence of proton nuclear magnetic resonance metabolomics in the cardiovascular arena as viewed from a clinical perspective. DOI: 10.1016/j.atherosclerosis.2014.09.024
  • Yang J et al. Nanotopographical induction of osteogenesis through adhesion, bone morphogenic protein cosignaling, and regulation of microRNAs. DOI: 10.1021/nn504767g
  • 2013
  • Robinson SW et al. FlyAtlas: database of gene expression in the tissues of Drosophila melanogaster. DOI: 10.1093/nar/gks1141
  • Sani E et al. Hyperosmotic priming of Arabidopsis seedlings establishes a long-term somatic memory accompanied by specific changes of the epigenome. DOI: 10.1186/gb-2013-14-6-r59
  • Tsimbouri PM et al. A genomics approach in determining nanotopographical effects on MSC phenotype. DOI: 10.1016/j.biomaterials.2012.12.019
  • 2012
  • Chintapalli VR et al. Functional correlates of positional and gender-specific renal asymmetry in Drosophila. DOI: 10.1371/journal.pone.0032577
  • Lee CM et al. Simultaneous non-negative matrix factorization for multiple large scale gene expression datasets in toxicology. DOI: 10.1371/journal.pone.0048238
  • Zhang T et al. Evaluation of coupling reversed phase, aqueous normal phase, and hydrophilic interaction liquid chromatography with Orbitrap mass spectrometry for metabolomic studies of human urine. DOI: 10.1021/ac2030738

Please click the link to obtain a copy of all the publications arising from Polyomics research, as of June 2021.

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