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10 december 2018

Approved FOM programme

Number 140.
Title Crowd management: the physics of DNA processing in complex environments (CMCE)
Executive organisational unit BUW
Programme management Prof.dr. N.H. Dekker
Duration 2013-2018
Cost estimate M€ 2,4

We aim to study the effect of crowding on the behavior of multi-protein machineries. In particular, by using state-of-the-art single-molecule approaches and by employing as model systems the processes of bacterial DNA replication and transcription, we will study how the proteins involved find specific sites on the DNA, move along the DNA, deal with DNA-based roadblocks, and dynamically exchange components with their environment, all in the presence of different forms of molecular crowding. By studying how these well-characterized systems and mechanisms respond to different levels of molecular crowding (both in solution as on the DNA), we aim to fill the gap between in vitro and in vivo experiments and aim to understand how the physics of crowding impacts biological processes at the molecular level. 

Background, relevance and implementation
For many decades, biophysicists and biochemists have studied molecular processes under highly idealized conditions: often a single species of protein is characterized under highly diluted conditions. The recent advent of single-molecule approaches has tremendously increased our capacity to delineate the biophysical mechanisms underlying the activity of proteins, but no significant effort has been undertaken yet to study how the crowded envi­ronment within a cell impacts these mechanisms. A better understanding of these effects will not only allow us to better place basic molecular mechanisms as derived from in vitro experi­ments into a cellular context, but will also allow us to define experimental conditions of in vitro experiments that do a better job of mimicking the inside of the cell.

We have structured our programme along four work packages. Within each of these work packages, two PhD students will be employed. These work packages will be bridged in the course of the programme by two so-called Synergy Projects (1.5 PhD positions each). To ensure the necessary interactions between the groups that are needed to make this programme successful, we organize three-monthly meetings between the group leaders and six-monthly meetings between all participants. Further, we plan to organize a Lorentz workshop during year three. 

The final evaluation will be based on the self-evaluation report initiated by the programme leader and is foreseen for 2019.

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