Project description
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.
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 (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology environmental biotechnology bioremediation bioreactors
- natural sciences biological sciences microbiology bacteriology
- engineering and technology other engineering and technologies microtechnology lab on a chip
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences biochemistry biomolecules proteins
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-COG - Consolidator Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2019-COG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
7610001 Rehovot
Israel
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.