Dr Ian Sudbery
Tel: 0114 222 2738
How do cells integrate information to make decisions about what genes should be expressed at a given time and in a given place? How do these processes malfunction to produce disease states? The correct regulation of gene expression is essential for the proper functioning of the cell, and incorrect regulation of genes is central to the mechanisms of many diseases. My interests rest in understanding how the many levels of eukaryotic gene regulation work together to perform these functions, using computational and functional genomics tools.
The role of microRNAs in regulatory networks
MicroRNAs (miRNAs) are short, single stranded RNAs that act to down regulate the expression of their targets by transcript destabilisation and translational inhibition. What roles to these molecules play in the information processing systems of the cell? How might these roles differ from that provided by transcriptional inhibitors? We know that miRNAs are found enriched in different topologies of network motifs than transcription factors. What might explain this?
Mathematical modelling suggests that miRNAs might threshold the expression of their target genes, only allowing protein production once transcription exceeds a particular rate. However, thus far experimental tests of this model are lacking in realistic in vivo settings. We are studying evidence that might speak to the applicability of this model in real biology, and studying the consequences of this behaviour on regulatory networks and the identification of miRNA targets.
Misregulation of chromatin structure in disease
A cell’s DNA does not exist as a single extended string of nucleic acids in the way often imagined, but rather is packed and folded in a myriad of ways to form a complex three dimensional structure. At least some of this structure is thought to be important for the regulation of gene expression. Transcription of metazoan genes is regulated by sequences known as enhancers which integrate diverse signals to make decisions about expression, and then communicate these decisions through their interactions with promoters. This communication is thought to take place via physical interactions between promoters and enhancers.
Together with collaborators from the Imperial University we are investigating how this three dimensional structure might contribute to the mis-regulation of gene expression in both monogenic disease and cancer using high-throughput, next-generation sequencing based assays of chromatin conformation.
Computational and functional genomics, eukaryotic gene expression
Level 3 Modules
MBB344 Genomic Science (Module Coordinator)
Level 1 Modules
MBB165 Practical Molecular Bioscience 1
- Macrophage polarisation associated with atherosclerosis differentially affects their capacity to handle lipid. Atherosclerosis. View this article in WRRO
- Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome. Molecular Cell. View this article in WRRO
- Proteins that physically interact with the phosphatase Cdc14 in Candida albicans have diverse roles in the cell cycle. Scientific Reports, 9. View this article in WRRO
- Alevin efficiently estimates accurate gene abundances from dscRNA-seq data. Genome Biology, 20. View this article in WRRO
- The m6A-methylase complex recruits TREX and regulates mRNA export. Scientific Reports, 8(1). View this article in WRRO
- UCHL3 Regulates Topoisomerase-Induced Chromosomal Break Repair by Controlling TDP1 Proteostasis. Cell Reports, 23(11), 3352-3365. View this article in WRRO
- UMI-tools: modeling sequencing errors in Unique Molecular Identifiers to improve quantification accuracy. Genome Research, 27, 491-499. View this article in WRRO
- Cell Cycle-Independent Phospho-Regulation of Fkh2 during Hyphal Growth Regulates Candida albicans Pathogenesis. PLOS Pathogens, 11(1), e1004630-e1004630. View this article in WRRO
- Identification of a candidate prognostic gene signature by transcriptome analysis of matched pre- and post-treatment prostatic biopsies from patients with advanced prostate cancer. BMC Cancer, 14(1). View this article in WRRO
- Next-generation Sequencing of Advanced Prostate Cancer Treated with Androgen-deprivation Therapy. European Urology, 66(1), 32-39.
- CGAT: computational genomics analysis toolkit. Bioinformatics, 30(9), 1290-1291.
- Sequencing depth and coverage: key considerations in genomic analyses. Nature Reviews Genetics, 15(2), 121-132.
- High-throughput analysis of candidate imprinted genes and allele-specific gene expression in the human term placenta. BMC Genetics, 11(1), 25-25.
- Systematic analysis of off-target effects in an RNAi screen reveals microRNAs affecting sensitivity to TRAIL-induced apoptosis. BMC Genomics, 11(1), 175-175.
- Deep short-read sequencing of chromosome 17 from the mouse strains A/J and CAST/Ei identifies significant germline variation and candidate genes that regulate liver triglyceride levels. Genome Biology, 10. View this article in WRRO
- Next-generation sequencing of vertebrate experimental organisms. Mammalian Genome, 20(6), 327-338.
- Apoptosis induced by environmental stresses and amphotericin B in Candida albicans. Proceedings of the National Academy of Sciences, 100(24), 14327-14332.
- CGAT-core: a python framework for building scalable, reproducible computational biology workflows. F1000Research, 8, 377-377.
- CGAT-core: a python framework for building scalable, reproducible computational biology workflows. F1000Research, 8, 377-377. View this article in WRRO
- Phosphoregulation of Nap1 Plays a Role in Septin Ring Dynamics and Morphogenesis in Candida albicans. mBio, 5(1).
- KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands. eLife, 1.
- Over-accessible chromatin links myeloma initiating genetic events to oncogenic transcriptomes and aberrant transcription factor regulatory networks.
Conference proceedings papers
- Oncogenic MAF in Co-Operation with IRF4 Confers Extensive Chromatin Re-Arrangement in Plasma Cells and Generates 'Neo-Enhancers' That Regulate Genes Critical for Myeloma Biology. Blood, Vol. 134(Supplement_1) (pp 3783-3783)
- Distinct Chromatin Accessibility Changes, Aberrant Transcription Factor Networks Combined with Novel Oncogenic Enhancers Characterise Myeloma-Initiating Genetic Events. Blood, Vol. 134(Supplement_1) (pp 1769-1769)
- BS25 Investigating the MIR-101-3P/TRIB1 axis in macrophage immunometabolism. Basic Science
- 201 Human oxidised phospholipid macrophages have high lipoprotein handling capabilities without readily forming unwanted foam cells. Heart, Vol. 103(Suppl 5) (pp A136.1-A136)
- Next generation sequencing of advanced non-castrate prostate cancer treated with docetaxel chemotherapy. BRITISH JOURNAL OF SURGERY, Vol. 101 (pp 63-63)
- Assessment of candidate imprinted genes in the human term placenta. JOURNAL OF MEDICAL GENETICS, Vol. 46 (pp S88-S88)