Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Dr Marieke Oudelaar completed her DPhil under the supervision of Doug Higgs and Jim Hughes (NDCLS, MRC WIMM). Her research describing chromosomal interactions within single cells has made a major contribution to the application of Chromosome Conformation Capture techniques.

Marieke.jpgI became interested in the field of gene regulation during my BSc at Utrecht University and MSc in Biomedicine at the Karolinska Institute. I find the processes that control gene activity both fascinating and important to understand, as they ultimately determine the identity of our cells and — if not functioning properly — are responsible for many diseases. I was fortunate to be awarded a Wellcome Trust scholarship in the Genomic Medicine and Statistics programme at the University of Oxford, which was aimed at students who were interested in combining ‘wet lab’ biological and ‘dry lab’ computational techniques in the field of genetics.

I joined Professors Jim Hughes and Doug Higgs' research groups in the WIMM: they had just published a description of a new technique called 'Capture-C, which can be used to study the structural conformation of DNA in our cells. As genes need to be physically activated by regulatory DNA sequences, such as enhancers and promoters, the structure of DNA inside the nucleus plays an important role in the regulation of gene activity. Capture-C provided a new way to analyse these structures at very high resolution.

However, a limitation of Capture-C is that it requires high cell numbers and therefore could not be applied to rare primary tissue types. To overcome this, I optimised the protocol to develop a Low-Input Capture-C technique.

Another limitation of Capture-C is that it’s only able to measure one contact point between two DNA sequences per cell. It could therefore tell if certain regulatory sequences could physically contact each other in the cell nucleus, but not how multiple enhancers and promoters interact together, and what kind of structures they form to activate genes.

To overcome this limitation, I built on the Capture-C technique to develop a new technique called Tri-C, which can measure three or more contacts per cell, and therefore translate our 2D picture of gene regulatory landscapes into 3D structures. By using this technique to study the well-characterised globin gene loci, I discovered that multiple enhancers and promoters form specific complexes in which they structurally cooperate to switch these genes on.

During my DPhil, the WIMM has provided a very stimulating research environment and I feel very grateful for the support, training and mentorship I received in the Hughes and Higgs groups. Since completing my DPhil, I have taken up a Junior Research Fellowship at University College in Oxford, which allows me to build and expand on my doctoral research and to continue my collaborative work with colleagues at the WIMM.