Project (Marieke Oudelaar)

Precise regulation of gene expression during development is a cornerstone for complex biological life. Mammalian gene expression patterns are controlled by the cis-regulatory elements of the genome, which include enhancers promoters. The spatial organization of the genome in the nucleus is important for communication between these elements. Enhancers and promoters interact in three-dimensional chromatin structures, which allow for specific communication between elements that are separated by large genomic distances. These enhancer-promoter interactions are important for gene regulation and perturbations of such interactions underly several congenital disorders and cancers.

In our lab, we study the interplay between the structural organization of the genome in the nucleus and the regulation of gene expression, and how perturbations in these processes contribute to disease. We develop and use state-of-the-art functional genomic techniques, in combination with genetic perturbations and computational approaches. We offer exciting research projects, usually involving a combination of experimental and computational work, in a stimulating and supportive research environment. We are looking for highly motivated students with a background in molecular biology, biochemistry, genetics or bioinformatics and a strong interest in gene regulation and genome organization.

• Ramasamy S, Aljahani A, Karpinska MA, Cao NTB, Cruz JN, Oudelaar AM (2022) The Mediator complex regulates enhancer-promoter interactions. bioRxiv https://doi.org/10.1101/2022.06.15.496245
  
• Aljahani A, Hua P, Karpinska MA, Quililan K, Davies JOJ, Oudelaar AM (2022) Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF. Nature Communications 13, 2139 https://doi.org/10.1038/s41467-022-29696-5
  
• Oudelaar AM and Higgs DR (2021) The relationship between genome structure and function. Nature Reviews Genetics 22: 154–168 https://doi.org/10.1038/s41576-020-00303-x
  
• Oudelaar AM, Beagrie RA, Gosden M, de Ornellas S, Georgiades E, Kerry J, Hidalgo D, Carrelha J, Shivalingam A, El-Sagheer AH et al (2020) Dynamics of the 4D genome during in vivo lineage specification and differentiation. Nature Communications 11: 2722, https://doi.org/10.1038/s41467-020-16598-7
  
• Oudelaar AM, Davies JOJ, Hanssen LLP, Telenius JM, Schwessinger R, Liu Y, Brown JM, Downes DJ, Chiariello AM, Bianco S et al (2018) Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains. Nature Genetics 50: 1744-1751. https://doi.org/10.1038/s41588-018-0253-2
  
• Davies JOJ, Oudelaar AM, Higgs DR, Hughes JR (2017) How best to identify chromosomal interactions: a comparison of approaches. Nature Methods 14: 125-134. https://doi.org/10.1038/nmeth.4146