Vertical Genomics/Hierarchical regulation analysis in yeast

The student will study how the cell regulates a number of metabolic processes whilst it is responding to a shift in nutrient concentration (phosphate; parallel PDRA projects do carbon and nitrogen starvation). Changes in transcription rate, mRNA & protein concentration/phosphorylation/synthesis rate, Vmax of/flux through, the corresponding enzymes are measured quantitatively and analyzed using hierarchical regulation analysis. This will quantify the extent to which the process is regulated through transcription, protein stability, metabolically, etc. Then: silicon cell modelling, and other external challenges.

Antitumor drugs and EGF Systems Biology (AstraZeneca collaboration)

EGF applied to tissue culture cells, the phosphorylation of the MAP kinase proteins being followed quantitatively in time, is the core assay. Systems Biology laws concerning controls by kinases and phosphatases on the dynamics of phosphorylation (amplitude, duration, area under the curve, etc.) will be tested and hopefully extended. EGF receptor mutation cells and drug-like molecules that act on the receptor and on the cascade will be studied. Hypothesis: drugs act best at sites to which control has shifted from the protein amplified by oncogenesis.

Skin ecosystems biology (Unilever collaboration)

Microorganisms living on the skin will be isolated and substituted by comparable model organisms in a laboratory model system. Their interactions will be determined by varying and measuring their abundances and studying the exometabolome. Metabolic activities in each organism will be followed and modelled. Regulation analysis will be performed for added substances relevant for skin.

From metabolomics up: data driven hypothesis generation put into the context of the yeast model

Yeast cells will be challenged by a number of different perturbations (substrates, osmotic strength), both in batch and in chemostat. The responses will be different. Using metabolomics and transcriptomics data, the student will be asked to analyze the patterns and to see if he can come up with hypotheses of a limited 'space' of regulation.

Systems Biology of translation in yeast

For protein synthesis in yeast, all components are available for an in vitro systems biology study. Concentrations will be varied and the effects analyzed using and developing a mathematical model for translation.

Yeast silicon cell: carbon and energy metabolism

Silicon cell type models are available for glycolysis. These will be extended to all major carbon and energy pathways, through modelling and experimental analysis. The student will examine possible 'metabolic apoptosis' states, e.g. when the pathways start at very low ATP/ADP ratio.

The dynamics of NFκB-mediated signal transduction

This will test the hypothesis that the time and space dependence of NFκB signalling contains multidimensional functional information. Patterns of NFκB signalling measured experimentally will be deconvoluted in space and time.