Project description DEENESFRITPL Gene expression at single-molecule resolution The EU-funded DYNOME project will study gene expression kinetics in individual cells at single-molecule resolution, for better understanding of how biological variability arises from the laws of statistics. The research combines several innovative approaches: a super-resolution detect-and-bleach strategy, multi-colour barcoding to monitor up to six genes in parallel, lineage tracking tools, and lab-on-a-chip bioreactors to control growth conditions. This biodynamics platform will allow monitoring of the gene expression dynamics at single-molecule level in single cells at the same time for several genes over many generations. As a model system, DYNOME will use stochastic decision-making events in bacteria and eukaryotic cells, involving a stochastic phenotype switch (Bacillus subtilis), development of non-genetic drug resistance (Escherichia coli), and cell cycle control (Saccharomyces cerevisiae). Deciphering cell individuality with kinetic models will be a breakthrough for development of drugs against bacterial invasions, for design of new functionalities in cells, and for the general concept of biological variabilities. Show the project objective Hide the project objective Objective Gene expression is an inherently stochastic process. Random expression bursts cause tremendous cell-to-cell variations in mRNA and protein levels. The consequences are beneficial in some instances, e.g. in cell differentiation, and harmful in others, e.g. in bacterial drug tolerance. A key interest in biology is therefore to decipher the kinetics that characterise this noise. What is the distribution of transcription rates in a cell population? Are gene expression dynamics heritable? Do gene networks communicate via the ‘Morse code’ of expression burst? Detailed answers to these questions are pending due to insufficient methods to temporally resolve gene expression noise at single-molecule resolution. A ‘transparent cell’ is needed for which transcription and translation kinetics is accessible for many genes in parallel. DYNOME is my answer to this challenge. DYNOME combines (i) a super-resolution detect-and-bleach strategy, (ii) multi-colour barcoding to monitor up to six genes in parallel, (iii) a lineage tracking tool, and (iv), lab-on-a-chip bioreactors to steer growth conditions. Using this innovative bio-dynamics platform, I will monitor gene expression dynamics at the single-molecule level for many genes in single cells at the same time over many generations. My targets for DYNOME are stochastic decision-making events in bacteria and in eukaryotic cells that include (i) a stochastic phenotype switch (B. subtilis), (ii) the development of non-genetic drug resistance (E. coli), and (iii) cell cycle control (S. cerevisiae). The results will reach far beyond these organisms. Decrypting cell-individuality with kinetic models will be a breakthrough both in basic and in applied sciences with impacts on the development of drugs against bacterial invasions, the design of new and useful functionalities in cells, and on our understanding of how biological variability arises from the laws of statistical physics. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologyengineering and technologyother engineering and technologiesmicrotechnologylab on a chipnatural sciencesphysical sciencesopticsmicroscopysuper resolution microscopynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistance Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2019-COG - ERC Consolidator Grant Call for proposal ERC-2019-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Coordinator WEIZMANN INSTITUTE OF SCIENCE Net EU contribution € 2 368 531,00 Address Herzl street 234 7610001 Rehovot Israel See on map 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 Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all WEIZMANN INSTITUTE OF SCIENCE Israel Net EU contribution € 2 368 531,00 Address Herzl street 234 7610001 Rehovot See on map 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 Other funding € 0,00
