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19 december 2018

Approved FOM programme

Number 110.
Title Spatial design of biochemical regulation networks (SPAT)
Executive organisational unit AMOLF + BUW
Programme management Prof.dr. M. Dogterom
Duration 2009-2014
Cost estimate M€ 3.1

The central aim of this programme is to understand how the performance of biochemical regulation networks depends on the spatial distribution of network components and the physical processes that facilitate signal transmission between them. We will focus specifically on the role of spatial separation, compartmentalization, diffusion, and cytoskeleton-based linear transport in the function and spatial design of gene- and protein regulation networks.

Background, relevance and implementation
Systems biology aims at a quantitative understanding of the collective, functional behavior of biomolecular systems (rather than of individual biomolecules) through an integrated experi­mental and theoretical approach. While the tight integration between quantitative experiments and theory is a longstanding cornerstone of physics research, this approach has traditionally been hampered in biology by a lack of knowledge about the molecular components that build biological systems. Due to recent substantial advances in the life sciences, large numbers of these components have now been identified and characterized. Increasingly, a physics-based approach is therefore not only feasible, but, arguably, an indispensable tool to make further progress.
The focus of this programme is on the operation of biochemical regulation networks at the cellular level, and in particular the spatial design principles of such networks. Biochemical regulation networks are the 'computational' modules controlling cellular functions. Recent studies on the operating principles of these networks are focused mainly on questions concerning their temporal dynamics and their performance with respect to sensitivity and robustness, i.e. resistance to noise and variations of operating parameters. Neither the spatial distribution of network components within cells nor the targeted, localized activation of network components is usually considered in these studies. However, regulation networks rely on physico-chemical interactions between genes and proteins that have to be brought into contact through physical processes such as diffusion and active transport along cytoskeletal tracks. The spatial distribution of network components, their localized activation, and the transport mechanisms that bring components together are therefore expected to have a profound influence on network performance.

The final evaluation of this programme will consist of a self-evaluation initiated by the programme leader and is foreseen for 2015. 

Please find a research highlight that was achieved in 2014 within this FOM programme here.