Projects

Ongoing Bioinformatics Projects

Center for Enzyme Innovation

An innovative new Research Centre to identify novel enzymatic solutions to environmental waste problems such as plastic

Portsmouth Heritage Hub

A network for researchers and stakeholders in local historical monuments and buildings to develop collaborative research projects with an aim to conserve, interpret, preserve and educate about our local heritage

Changes in microbial communities of Cliona celeta during observed changes in sponge health

Analysis of changes in microbial communities of Cliona celeta from Skomer Marine Nature Reserve during observed changes in sponge health using 16s rDNA sequencing

Genotyping of Ancient DNA from Crew Members from the Mary Rose

Genotyping of ancient DNA from crew members from the Mary Rose to identfy phenotypic traits and disease traits

Development of Bioinformatics Tools

We are currently working on a number of in-house bioinformatics tools to make these available to the wider research community

Effects of Anti-Fouling Coatings on Marine Biofilms

Metatranscriptomic analysis of marine biofilm composition on commercially available and novel anti-fouling substrates

Effects of Radiation Exposure in the Environment

Identification of differentially regulated gene pathways as a result of radiation exposure

Gene Expression Profiling of Duchenne Muscular Dystrophy

Differential gene expression analysis in a model of Duchenne Muscular Dystrophy

The Role of Variant Histones in Xenopus Development

Transcriptional profiling of variant histone knockdowns in Xenopus laevis

Transcriptome Profiling Of The Radula of Patella vulgata

Identification of key gene pathways involved in the formation of the radula in Patella vulgata (common limpet)

Publications

More Publications

Sox2 is a master transcriptional regulator of embryonic development. In this study, we determined the protein interactome of Sox2 in the chromatin and nucleoplasm of mouse embryonic stem (mES) cells. Apart from canonical interactions with pluripotency-regulating transcription factors, we identified interactions with several chromatin modulators, including members of the heterochromatin protein 1 (HP1) family, suggesting a role of Sox2 in chromatin-mediated transcriptional repression. Sox2 was also found to interact with RNA binding proteins (RBPs), including proteins involved in RNA processing. RNA immunoprecipitation followed by sequencing revealed that Sox2 associates with different messenger RNAs, as well as small nucleolar RNA Snord34 and the non-coding RNA 7SK. 7SK has been shown to regulate transcription at regulatory regions, which could suggest a functional interaction with Sox2 for chromatin recruitment. Nevertheless, we found no evidence of Sox2 modulating recruitment of 7SK to chromatin when examining 7SK chromatin occupancy by Chromatin Isolation by RNA Purification (ChIRP) in Sox2 depleted mES cells. In addition, knockdown of 7SK in mES cells did not lead to any change in Sox2 occupancy at 7SK-regulated genes. Thus, our results show that Sox2 extensively interact with RBPs, and suggest that Sox2 and 7SK co-exist in a ribonucleoprotein complex whose function is not to regulate chromatin recruitment, but might rather regulate other processes in the nucleoplasm.
Experimental Cell Research, Vol. 381, No. 1, 01.08.2019, p. 129-138.
Details PDF Dataset

7-methylguanosine (m7G) is present at mRNA caps and at defined internal positions within tRNAs and rRNAs. However, its detection within low-abundance mRNAs and microRNAs (miRNAs) has been hampered by a lack of sensitive detection strategies. Here, we adapt a chemical reactivity assay to detect internal m7G in miRNAs. Using this technique (Borohydride Reduction sequencing [BoRed-seq]) alongside RNA immunoprecipitation, we identify m7G within a subset of miRNAs that inhibit cell migration. We show that the METTL1 methyltransferase mediates m7G methylation within miRNAs and that this enzyme regulates cell migration via its catalytic activity. Using refined mass spectrometry methods, we map m7G to a single guanosine within the let-7e-5p miRNA. We show that METTL1-mediated methylation augments let-7 miRNA processing by disrupting an inhibitory secondary structure within the primary miRNA transcript (pri-miRNA). These results identify METTL1-dependent N7-methylation of guanosine as a new RNA modification pathway that regulates miRNA structure, biogenesis, and cell migration.
Molecular Cell, Vol. 74, 20.06.2019, p. 1-13
Details PDF Dataset

Pathophysiology of Duchenne Muscular Dystrophy (DMD) is still elusive. Although progressive wasting of muscle fibres is a cause of muscle deterioration, there is a growing body of evidence that the triggering effects of DMD mutation are present at the earlier stage of muscle development and affect myogenic cells. Among these abnormalities, elevated activity of P2X7 receptors and increased store-operated calcium entry myoblasts have been identified in mdx mouse. Here, the metabotropic extracellular ATP/UTP-evoked response has been investigated. Sensitivity to antagonist, effect of gene silencing and cellular localization studies linked these elevated purinergic responses to the increased expression of P2Y2 but not P2Y4 receptors. These alterations have physiological implications as shown by reduced motility of mdx myoblasts upon treatment with P2Y2 agonist. However, the ultimate increase in intracellular calcium in dystrophic cells reflected complex alterations of calcium homeostasis identified in the RNA seq data and with significant modulation confirmed at the protein level, including a decrease of Gq11 subunit α, plasma membrane calcium ATP-ase, inositol-2,4,5-trisphosphate-receptor proteins and elevation of phospholipase Cβ, sarco-endoplamatic reticulum calcium ATP-ase and sodium‑calcium exchanger. In conclusion, whereas specificity of dystrophic myoblast excitation by extracellular nucleotides is determined by particular receptor overexpression, the intensity of such altered response depends on relative activities of downstream calcium regulators that are also affected by Dmd mutations. Furthermore, these phenotypic effects of DMD emerge as early as in undifferentiated muscle. Therefore, the pathogenesis of DMD and the relevance of current therapeutic approaches may need re-evaluation.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 24.01.2019
Details PDF Dataset

We recently identified the splicing kinase gene SRPK1 as a genetic vulnerability of acute myeloid leukemia (AML). Here, we show that genetic or pharmacological inhibition of SRPK1 leads to cell cycle arrest, leukemic cell differentiation and prolonged survival of mice transplanted with MLL-rearranged AML. RNA-seq analysis demonstrates that SRPK1 inhibition leads to altered isoform levels of many genes including several with established roles in leukemogenesis such as MYB, BRD4 and MED24. We focus on BRD4 as its main isoforms have distinct molecular properties and find that SRPK1 inhibition produces a significant switch from the short to the long isoform at the mRNA and protein levels. This was associated with BRD4 eviction from genomic loci involved in leukemogenesis including BCL2 and MYC. We go on to show that this switch mediates at least part of the anti-leukemic effects of SRPK1 inhibition. Our findings reveal that SRPK1 represents a plausible new therapeutic target against AML.
Nature Communications, Vol. 9, No. 1, 5378, 19.12.2018
Details PDF Dataset

In response to genotoxic stress, cells activate a signaling cascade known as the DNA damage checkpoint (DDC) that leads to a temporary cell cycle arrest and activation of DNA repair mechanisms. Because persistent DDC activation compromises cell viability, this process must be tightly regulated. However, despite its importance, the mechanisms regulating DDC recovery are not completely understood. Here, we identify a DNA-damage-regulated histone modification in Saccharomyces cerevisiae, phosphorylation of H4 threonine 80 (H4T80ph), and show that it triggers checkpoint inactivation. H4T80ph is critical for cell survival to DNA damage, and its absence causes impaired DDC recovery and persistent cell cycle arrest. We show that, in response to genotoxic stress, p21-activated kinase Cla4 phosphorylates H4T80 to recruit Rtt107 to sites of DNA damage. Rtt107 displaces the checkpoint adaptor Rad9, thereby interrupting the checkpoint-signaling cascade. Collectively, our results indicate that H4T80ph regulates DDC recovery.
Molecular Cell, Vol. 72, No. 4, 15.11.2018, p. 625-635.e4
Details PDF Dataset

Resources

Sequencing Facilities

A list of commercial and academic sequencing facilities used by members of the faculty

Bioinformatics Tools

A list of commonly used tools for bioinformatics analyses

How To Use R

A tutorial for the use of the statistical programming language R, with a Bioinformatics leaning.

Software

NGS Pipeline

A pipeline for analysis of NGS data

Recent & Upcoming Lectures

Recent Posts

Blog Bioinformatics, University of Portsmouth, Welcome, Portsmouth Heritage Hub
On Friday 7th June, the Mary Rose Museum in the Portsmouth Historic Dockyard hosted the inaugural meeting of the Portsmouth Heritage Hub (PHH). The workshop aimed to bring together around 30 researchers from the University of Portsmouth with interests and expertise in the heritage field, with members of 15 organisations associated with local historical artefacts, architecture and monuments in Portsmouth and the surrounding area. It was a fantastic opportunity to foster collaborative research networks between people with the skills and expertise to solve problems, with stakeholders in our history with problems to solve.

CONTINUE READING

Blog Bioinformatics, University of Portsmouth, Welcome
Welcome to the University of Portsmouth Bioinformatics Group website. I set up this group having recently moved from the University of Cambridge, and hope to develop the group further over the coming years. I am going to aim to post regularly on this blog with posts relating to data analysis, experimental design, advances in sequencing technology, and other related matters that may be of interest to visitors. I have kicked things off with a tutorial for those of you that are interested in learning how to use the statistical programming language R.

CONTINUE READING

Contact