Stefan Schoenfelder
Dr Schoenfelder holds a Babraham Institute Career Progression Fellowship which provides two years of support for his research.
Research Summary
Functional organisation of the genome in 3D
98% of the DNA in our body is non-coding, i.e. does not carry the information needed to build proteins. Non-coding has sometimes been equated with ‘non-functional’, or called ‘junk’ in the past; today we know that this is far from the truth. Scattered throughout non-coding DNA is a plethora of so-called regulatory elements, including enhancers, silencers and insulators. These regulatory elements function like molecular switches to control which genes are active (and thus produce proteins) in which cells. This process of gene expression control is vital to allow cells – which all contain the same genes – to specialise to carry out different tasks, and to help them respond to changes.
Enhancers are a type of regulatory element that control gene expression over long distances. They contact their target genes via chromosomal interactions, often bridging large distances in the genome, with the intervening DNA ‘looping out’. To understand how enhancers work, we study them in the context of the three-dimensional organisation of the genome.
Our aim is to find regulatory elements and to understand which genes they control. We also aim to uncover the molecular mechanisms by which regulatory elements find their target genes in the three-dimensional space of the cell nucleus, and to understand how altering the function of regulatory elements can lead to developmental malformations and disease.
We study these questions in pluripotent stem cells – cells that have the potential to create all cell types in the adult body. We use a combination of molecular, genetic, biochemical and imaging approaches to study pluripotent stem cells in their ‘ground state’, and when they start to form new cell types – a process called cell lineage specification.
Techniques and Methods
Through high-resolution mapping and experimental perturbation of the spatial genome architecture, we aim to reveal gene regulatory principles that underpin cell states and cell fate transitions. This may ultimately pave the way for us to experimentally engineer 3D genome folding to achieve predictable outcomes on gene expression and cell fate choice, with potential implications for gene therapy and regenerative medicine.
Latest Publications
Transcription-dependent cohesin repositioning rewires chromatin loops in cellular senescence. Nature communications, 11, 1, 27 Nov 2020 PMID: 33247104 |
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High-resolution three-dimensional chromatin profiling of the Chinese hamster ovary cell genome. Biotechnology and bioengineering, 1, 1, 23 Oct 2020 PMID: 33095445 |
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Cohesin-Dependent and -Independent Mechanisms Mediate Chromosomal Contacts between Promoters and Enhancers. Cell reports, 32, 3, 21 Jul 2020 PMID: 32698000 |