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10 december 2018

Closed FOM programme

Number 103.
Title DNA in action: Physics of the genome (DNAA)
Executive organisational unit BUW
Programme management Prof.dr.ir. G.J.L. Wuite
Duration 2008-2012
Cost estimate M€ 4.2

Our objective is to resolve the physical mechanisms that organize, regulate and maintain the DNA within the chromatin structure.

Background, relevance and implementation
The physical basis of all life is the ability to store, selectively read out, duplicate and transmit genetic information. In order to achieve these goals the DNA that carries this information within each living cell is organized spatially by proteins into a highly intricate, hierarchical and dynamical structure known as chromatin - This amazing structure strikes a balance between the need for compaction and the need for accessibility by genomic processes (i.e. transcription, replication, repair and recombination of DNA). Understanding the constant (re)organization of the genome within the chromatin structure is needed to grasp the physical basis of life in all (!) eukaryotes, including man. Despite this, there is a remarkable paucity in our understanding of properties and behavior of chromatin.

The timing is highly opportune, because - despite the progress biologists have made in identifying the many key players that interact with the genome – to date little is known about the physical processes that underpin the dynamic control of the DNA in the chromatin structure. Fortunately, over the past few years biophysicists have developed highly sophisticated single-molecule techniques that are ideally suited for investi­gations of the biophysical mechanisms of the protein machines that arrange and process the chromatin structure. The research groups united in this consortium have played a prominent role in the international research on this topic and combine a unique array of know-how needed to address this important problem. A major challenge for biophysical research in the coming years is to attain a higher level of complexity and study the interplay of different proteins in complex mechanisms. This programme bundles and focuses the existing excellence in nucleoprotein biophysics in the Netherlands and combines it with the expertise provided by selected eminent theoreticians and biologists to make this step and help resolve the physical mechanisms that organize, regulate and maintain the genome within the dynamic chromatin structure. Because malfunction of chromatin plays an important, but still poorly understood role in human health, including aging and cancer, we anticipate that results of our research will find applications in the biomedical and biotechnological field.

The final evaluation of this programme will consist of a self-evaluation initiated by the programme leader and is foreseen for 2013.

Please find a research highlight that was achieved in 2013 within this FOM programme here.