MicroRNA degradation and turnover in plant model systems
MicroRNAs can be differentially expressed in response to stressful or unfavourable conditions. There is much work to show which mechanisms are utilised to switch on microRNA expression. Less well understood is how microRNAs are degraded and switched off. We investigate these degradation mechanisms and gene networks.
The latest Research Excellence Framework (REF 2014) ranked 80% of research output by the School of Biological Sciences to be "world-leading" or "internationally excellent". The Dalmay Laboratory contributes to this with projects being funded by the European Commission, UK Research Councils and charities. The group's primary interests are in RNA silencing. The group's research uses both plant and animal systems (Arabidopsis, tomato, human, mouse, chicken, fruit fly, etc.). The major theme of the laboratory is the role of microRNAs in various biological processes.
Research
Structure specific cleavage of Y RNAs
Next generation sequencing has revealed a slightly longer class of small RNAs that are 30-34 nucleotides long. The biogenesis of these longer small RNAs seems to be diverse and is not well understood. We have characterized such longer small RNAs generated from Y RNAs in mammalian cells and found that it is different from microRNA biogenesis. Results from a high-throughput mutagenesis approach suggest that the secondary structure of the Y RNA, rather than its sequence, determines where the cleavage happens that liberates the small RNAs from the 3' end of Y RNAs. We aim to validate these results and also to apply a high-throughput mutagenesis screen on the 5' region of the Y RNA to study the production of small RNAs from that end of the molecule.
RNA-mediated regulation of gene expression in bone cancer
Primary bone cancer is derived from the malignant transformation of primitive mesenchymal cells. Bone cancer is a “less common cancer” representing 0.2% of total cancer incidence. A recent report by the National Cancer Intelligence Network showed the percentage of total cancer deaths from less common cancers has increased to an all-time high of 54%. Bone cancer is most prevalent in children and young adults. A new diagnosis is made every other day in the UK. The five-year survival rate is 25-50% depending on cancer stage at diagnosis. Our early work has shown that bone cancer cells deliberately switch off the production of specific tRNA fragments which are known to interact with and inhibit the action of oncogenic proteins. We have re-modulated the expression of these tRNA fragments in 3D models of bone cancer and shown that cancer progression can be halted.
RNA "beacons" in cancer diagnostics
Partner in the Europe-wide SAPHELY project consortium for the development and preclinical validation of a nanophotonic-bases handheld point-of-care analysis device for the minimally invasive early diagnosis of cancer. The diagnosis is based on the detection of microRNA biomarkers in a small volume blood sample by molecular beacon capture probes appended by a high refrative index nanoparticle, which undergoes a conformational change in the presence of the biomarker, which in turn is detected by photonic bandgap sensing structures.
The UEA Small RNA Workbench - publicly available software for bioinformatics and computational biology
Advances in next generation sequencing technologies are producing increasingly large numbers of small RNA (sRNA) reads per sample at a fraction of the cost of previous methods. Many bioinformatics tools do not scale accordingly, are cumbersome, or require extensive support from bioinformatics experts. Researchers need user-friendly, robust tools, capable of not only processing large sRNA datasets in a reasonable time frame but also presenting the results in an intuitive fashion and visualizing sRNAgenomic features. We developed The UEA sRNA Workbench, a suite of tools that is in a downloadable format and with several enhanced and additional features compared to other software available.
Diet induced changes of microRNA expression in colorectal cancer
Compounds found in the diet can act on our genes and have a major impact on our health. We are elucidating these pathways in human cancer cells with a major focus on how microRNAs are involved in these processes. We have strong ties to the Institute of Food Research on the Norwich Research Park where this work can utilise the latest technology in nutrigenomics and diet-related research.
Role of the transcriptome in caste determination of bumble bees
Bumble bees, like other bees, ants and wasps, are fascinating social animals which have distinct castes. These castes include a queen that does most of the reproduction, and workers that do most of the day-to-day colony maintenance tasks. Workers and queens all have the same genomes, yet they are biologically very distinct from each other (having separate behaviour, morphology, and physiology). Caste determination in social insects is broadly analogous to cellular development in multicellular species where all of the cells in a single organism have the same genome, yet they have very different functions from each other. We use RNA sequencing approaches across several bumble bee species to identify what causes these changes in social insects and to gain a broader understanding of what causes multiple phenotypes to develop from the same genotype in all organisms.
MicroRNAs in brain and central nervous system development
MicroRNAs play a huge role in developing the brain and central nervous system during embryonic development. We use locked nucleic acids to trace the expression of various microRNAs during brain development and characterise the gene networks involved. Some of these microRNAs are differentially expressed in diseases of the central nervous system and spinal cord in adulthood.
