Stevenson Junior Research Fellow in Biochemistry
My research focuses on the structural organisation of DNA inside our cells. Human cells contain large amounts of DNA, which need to be compacted and folded to fit inside cell nuclei. Only a small part of our DNA (~2%) consists of genes. Their activity needs to be precisely regulated, to enable individual cells to express the appropriate set of genes required for their specific functions. Regulatory sequences contained in the remaining part of the DNA play a key role in controlling gene activity levels and physically interact with the genes they regulate to switch them on. The three-dimensional organisation of the DNA within our cells is therefore crucial for cell functioning. Better understanding of this process is important, as disruption of DNA structures results in misregulation of gene activity and contributes to human disease. My work focuses on the use, development and computational analysis of Chromosome Conformation Capture techniques to explore the three-dimensional structure of DNA. Using the haemoglobin genes, which are gradually activated in developing blood cells, as a model system, I try to understand how changes in the structural organisation of genes relate to their level of activity.
Oudelaar, A.M., Beagrie, R.A., Gosden, M.E., De Ornellas, S., Georgiades, E., Kerry, J., Hidalgo, D., Carrelha, J., Shivalingam, A., El-Sagheer, A.H., et al. (2020). Dynamics of the 4D genome during lineage specification, differentiation and maturation in vivo. BioRxiv, doi:10.1101/763763.
Chiariello, A.M., Bianco, S., Oudelaar, A.M., Esposito, A., Annunziatella, C., Fiorillo, L., Conte, M., Corrado, A., Prisco, A., Larke, M.S.C., et al. (2020). A Dynamic Folded Hairpin Conformation Is Associated with α-Globin Activation in Erythroid Cells. Cell Reports 30, 2125-2135.e2125.
Oudelaar, A.M., Harrold, C.L., Hanssen, L.L.P., Telenius, J.M., Higgs, D.R., and Hughes, J.R. (2019). A revised model for promoter competition based on multi-way chromatin interactions at the α-globin locus. Nature Communications 10, 5412.
Oudelaar, A.M., Davies, J.O.J., Hanssen, L.L.P., Telenius, J.M., Schwessinger, R., Liu, Y., Brown, J.M., Downes, D.J., Chiariello, A.M., Bianco, S., et al. (2018). Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains. Nature Genetics 50, 1744–1751.
Brown, J.M., Roberts, N.A., Graham, B., Waithe, D., Lagerholm, C., Telenius, J.M., De Ornellas, S., Oudelaar, A.M., Scott, C., Szczerbal, I., et al. (2018). A tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions. Nature Communications 9, 376.
Oudelaar, A.M., Davies, J.O.J., Downes, D.J., Higgs, D.R., and Hughes, J.R. (2017). Robust detection of chromosomal interactions from small numbers of cells using low-input Capture-C. Nucleic Acids Research, 45 (22), e184-e184.
Oudelaar, A.M., Downes, D.J., Davies, J.O.J., and Hughes, J.R. (2017). Low-input Capture-C: A Chromosome Conformation Capture Assay to Analyze Chromatin Architecture in Small Numbers of Cells. Bio-Protocol, 7 (23).
Oudelaar, A.M., Hanssen, L.L.P., Hardison, R.C., Kassouf, M.T., Hughes, J.R., and Higgs, D.R. (2017). Between form and function: the complexity of genome folding. Human Molecular Genetics 26, R208–R215.
Hanssen, L.L.P., Kassouf, M.T., Oudelaar, A.M., Biggs, D., Preece, C., Downes, D.J., Gosden, M., Sharpe, J.A., Sloane-Stanley, J.A., Hughes, J.R., et al. (2017). Tissue-specific CTCF-cohesin-mediated chromatin architecture delimits enhancer interactions and function in vivo. Nature Cell Biology 19, 952–961.
Davies, J.O.J., Oudelaar, A.M., Higgs, D.R., and Hughes, J.R. (2017). How best to identify chromosomal interactions: a comparison of approaches. Nature Methods 14, 125–134.
Hay, D., Hughes, J.R., Babbs, C., Davies, J.O.J., Graham, B.J., Hanssen, L.L.P., Kassouf, M.T., Oudelaar, A.M., Sharpe, J.A., Suciu, M.C., et al. (2016). Genetic dissection of the α-globin super-enhancer in vivo. Nature Genetics 48, 895–903.