Knop Group

Previous and current research

Our group is interested in the various cellular processes that underlie the sexual cycle of budding yeast (mating and meiosis). In the past we have addressed the meiosis-specific pathways that regulate spore morphogenesis with respect to spindle pole body function membrane formation and morphogenesis and cytokinesis. We mainly focused on the processes that regulate spore morphogenesis in comparison to cell division by bud formation. Among other things, we concentrated on the regulation of spindle pole function in controlling vesicle fusion, in the initiation of spore morphogenesis and on membrane shaping of the spore.

Mating is another important aspect of the life cycle of yeast. How do yeast cells faithfully find amating partner? We study the MAP kinase signal transduction pathway that underlies signal transduction during mating. We established Fluorescence (Cross-) Correlation Spectroscopy (FCCS) and FLIM to work with yeast cells. These new quantitative imaging methods enable us to measure protein complex formation and to visualise the activity of the MAP kinases. This yields important new insights into the dynamics and the spatial organisation of the signalling process.

Future projects and goals

We continue to use quantitative microscopy approaches and subsequently expand our investigation to three interconnected MAP kinase signalling pathways by using semi-high throughput screening microscopy to quantify protein concentration, protein-protein interaction and protein localisation of all the major components involved (figure 1). We consider both quiescent and signalling conditions. The goal is to enhance our understanding of the spatial and dynamic organisation of the signaling processes, which will help us derive and further develop quantitative models of the processes that regulate signalling through these pathways.

Our work on meiosis has gradually shifted to questions that relate to the role und function of genome recombination. As a model, we use computer simulations of populations of yeast-like genomes that undergo yeast-like live cycles. Here we address the role of meiosis and recombination and the impact of genome architecture on handling deleterious mutational load (figure 2). To complement these approaches, we use yeast as a model for experimental evolutionary studies where we address the consequences of random mutations on fitness, and on the role of meiosis and recombination to purge deleterious load. Furthermore, we study a novel yeast species with similar life-cycle properties to S. cerevisiae, but which has one notable and most interesting difference: this species appears to not recombine its genome during meiosis. We use genome sequencing and experimental approaches to address how this species performs meiosis I and to understand the impact of absent recombination on the evolution of the genome.