Molecular genomics studies

• Assessment of global changes in gene transcription, mRNA translation and microRNA (miRNA) expression using microarrays in both in vitro and in vivo including
  
  • The development of multidrug resistance in vitro
  • Mechanisms of toxicity leading cholestasis in the liver
  • Mechanisms of cardiotoxicity
  • Effect of chemicals on sperm development and the male germline

• Role of miRNA mediated mRNA regulation by assessment of miRNA expression and its relationship to altered mRNA translation in the studies as shown.

• Chemical toxicity in the male germline and role of altered miRNA expression in the potential transmission of epigenetic marks in the germline. This project the subject of an award to Dr Emma Taylor from the CEFIC/LRI program.

• Involvement of reactive oxygen species in cardio and liver toxicity in vivo using model quinone species.

• Transcriptional, translation and miRNA changes associated with chemical and drug toxicity to inform on the mechanism of toxicity and provide biomarkers for early detection.
  • Mechanism of doxorubicin cardiotoxicity
  • Mechanism of toxicity of 14 drugs that failed in early stage toxicity testing (FP6 Innomed PredTox project).
  • Mechanisms associated with troglitazone cardiotoxicity

Bioinformatics

• Connectivity mapping of genomics datasets to detect pharmacological and toxicological properties in new chemical entities  

Resource provision

• Providing microarrays on a collaborative basis and assistance with experimental design and data analysis. Databases showing available microarrays are available on this website.
• Our developed methods and software implementation are available from this website.

• We support the provision of Arraytrack from the USFDA on our own server for microarray data analysis.

• Providing tools for the analysis of miRNA clusters and miRNA sequence information etc.

Collaborations external to the MRC Toxicology Unit

 

We have collaborations with the following groups (Listed alphabetically):

Dr Toby Athersuch (Imperial College, London) – Metabonomics of various studies to understand mechanisms of toxicity (some work with naphthoquinones in press).

Prof. M. Barer (University of Leicester) – Characterisation of the microbiome in patient samples using the 16S chromosomal region. Funding MRC project grant.

Dr Martin Bushell (University of Nottingham) – Genomics of the miRNA control of mRNA translation.

Dr Shaun Cowley (University of Leicester) – Characterisation of transcriptome changes in ES cells following HDAC knockout.

Dr Cornelia De Moor (University of Nottingham) –Genomics aspects of cytoplasmic polyadenylation in NIH3T3 cells (BBSRC funded).

Prof Yuri Dubrova (University of Leicester) – Gene and miRNA regulation associated with altered epigenetics and minisatellite instability in the male germline due to chemical exposure. Funding – this work is a two way collaboration funded in both laboratories. In particular this collaboration forms part of the work of the CEFIC/LRI award to Dr Emma Taylor.

Prof Andreas Gescher and Dr Stewart Sale (University of Leicester) – Gene expression change associated with the suppression by dietary fibre of colon adenoma formation in the min mouse (Industry funded).

Dr Ursula Lutz (University of Wϋrtzburg) – metabolism of naphthoquinone species (work in press).

Prof. Harry Moore (University of Sheffield) - maintenance and differentiation of Embryonic Stem Cells along parts of the male germline and role of miRNA in this process. This collaboration forms part of the CEFIC/LRI award to Dr Emma Taylor.

Dr Catrin Pritchard (University of Leicester) – maintenance and differentiation of Embryonic Stem Cells along the cardiomyocyte and hepatocytes lineages. This collaboration is part of an Integrated Toxicology Training Partnership (ITTP) to Dr T. Gant and also with the CEFIC/LRI award to Dr Emma Taylor.

Dr Frederike Teichert and Dr Raj Singh (University of Leicester) – Mass spectrometry analysis of 8-oxo-dG and creatine in urine (work in press).

Dr Simon Wagner (University of Leicester) – Role of post-transcriptional gene regulation in Chronic Lymphocytic Leukaemia. This collaboration is awaiting the outcome of current grant applications.

Prof Anne Willis (University of Nottingham) – Genomics aspects of regulation of gene expression at the level of protein synthesis (BBSRC funded).

Dr Mariuca Vasa-Nicotera (University of Leicester) – Role of miRNAs in the senescence program of Cardiac endothelial cells (subject to a current funding application).

Many other informal collaborations in genomics, and particularly bioinformatics are ongoing and we apologise if any of these have been omitted from this list.