Objective
Despite the ubiquity of genome sequence data, unravelling the contributions of genetic variation to phenotypic diversity remains one of the greatest challenges in genomics. This is partly due to our very limited knowledge of how multiple variations combine to create phenotypes. There is a clear need for a systematic, perturbation-based approach to study the phenotypic consequences of genetic variants in different genomic and environmental contexts. Previous efforts have primarily used loss-of-function or overexpression approaches, but it is known that subtle, naturally occurring variants have the most relevance for complex, quantitative traits. Our proposal aims to dissect these effects by systematically engineering and functionally profiling naturally occurring single-nucleotide variants (SNVs) and small insertion/deletion polymorphisms (indels) in the S. cerevisiae species in three diverse genetic backgrounds. To generate such an unprecedented collection, we will apply a high-throughput CRISPR approach that allows rapid isolation of sequence-verified strains. DNA barcodes integrated into the genome of each strain will enable pooled, competitive growth, which will reveal how variants modulate fitness as a function of environment and genetic background. We will test our collection for pairwise and higher order interactions, assay their impact on cellular processes and dissect pleiotropic roles of highly connected genes. Our work will circumvent the key limitations in current high-throughput genome editing screens and enable the largest interrogation of the functional impact of genetic variation in different environmental and genetic contexts to date. The combined insights and tools generated by our work will aid in developing predictive models of the effects of genetic variation within specific environmental and biological contexts, providing guiding principles for understanding the consequences of human genetic variation.
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.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- engineering and technology electrical engineering, electronic engineering, information engineering information engineering telecommunications telecommunications networks mobile network
- natural sciences biological sciences genetics nucleotides
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences genetics genomes
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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)
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.
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-ADG - Advanced 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-2016-ADG
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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.
69117 Heidelberg
Germany
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.