Abstract
How organisms evolve is a fundamental question with implications for human health. Here I want to mechanistically understand how biochemical networks, which make up an organism, reorganize during evolution, without compromising fitness. In vivo, all biochemical networks are connected, which complicates the study of finding out how, or simply, for which biochemical network, mutations are adaptive. Therefore, I will isolate one biochemical network by building an in vitro model system. With this system I will identify basic network structures, which allow network evolution without loss of function. In parallel I will test these mechanisms in vivo. I will focus on symmetry breaking in Saccharomyces cerevisiae. This is a functionally conserved process, which results in a polarized protein pattern on the cell membrane and is the first step in polarity establishment. First, I will build a minimal evolvable network. I will encapsulate proteins in lipid droplets and measure the networks fitness, which I define as the rate at which a single protein spot forms on the droplet membrane. In my definition of a minimal evolvable network one of the components can be duplicated without compromising the networks fitness. This mimics the in vivo situation, where gene duplication enables network evolution. Next, I will study how increasing the number of added components affects evolvability of the network. In parallel I will investigate the relevance of my in vitro findings for evolvability of biochemical networks in the complexity of a living cell. I will use live cell microscopy and modelling to investigate how duplication of components for symmetry breaking affect connected biochemical networks. My combined in vitro and in vivo findings will reveal how the symmetry breaking network structure allows evolutionary reorganization. My expertise in in vitro systems, modelling, biophysics and evolution makes me uniquely qualified for this ambitious project.
Netherlands