Objective A key question in biology is how cells at different locations communicate through signalling molecules so that cells at the right place and time turn on the right genes. Such coordination is vital for many processes including the development of all embryos. A common set of strategies that cells from distinct organisms use to coordinate their gene expression has long been elusive. Finding it requires quantifying how two key factors, the spatial locations of cells and the genetic circuits that control the cells’ secretion of signalling molecules, each affects cells' gene expressions. This has been challenging because their effects are often intertwined in complex ways. To overcome this challenge, I will assemble budding yeasts into multicellular structures component-by-component in a bottom-up manner, from building genetic circuits to arranging cells in space. I will build genetic circuits whose motifs commonly occur in natural systems. The yeasts will use the genetic circuits to control secretion and sensing of three distinct signalling molecules for communication. Using adhesive proteins and light-inducible genes, I will assemble multiple yeast strains, each with a unique genetic circuit, into a single two- and three-dimensional multicellular structure. The structures will mimic various sizes, shapes, and arrangements of cells found in nature. I will then switch on the circuits in these cells to initiate communication between cells. Different amounts of signalling molecules will cause the cells to make different amounts of fluorescent proteins. By measuring the fluorescence of cells at different locations over time and then correlating them, I will infer the degree of cell-cell coordination. I will build mathematical models to guide the experiments. By finding which combinations of genetic circuits and spatial arrangements of cells enable cell-cell coordination of gene expressions, I will reveal design principles of multicellular systems that have been elusive. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesdevelopmental biologymedical and health sciencesclinical medicineembryologynatural sciencesmathematicsapplied mathematicsmathematical model Keywords Design principles of genetic circuits Quantitative biology Biophysics Network motifs Design principles of multicellular systems Collective behaviours Cell circuits Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-StG-2015 - ERC Starting Grant Call for proposal ERC-2015-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution TECHNISCHE UNIVERSITEIT DELFT Net EU contribution € 1 500 000,00 Address STEVINWEG 1 2628 CN Delft Netherlands See on map Region West-Nederland Zuid-Holland Delft en Westland Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 500 000,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all TECHNISCHE UNIVERSITEIT DELFT Netherlands Net EU contribution € 1 500 000,00 Address STEVINWEG 1 2628 CN Delft See on map Region West-Nederland Zuid-Holland Delft en Westland Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 500 000,00
