YEFF · Comprehensive analysis of yeast expression-fitness functions (EFFs)
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-05-01 → 2020-06-25
- EU contribution
- €170,122
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Comprehensive analysis of yeast expression-fitness functions (EFFs)
The project focused on a systematic understanding of how changes in the functional abundance of genes affect organismal fitness. The proper abundance or expression of gene products is critical to virtually all cellular processes, from DNA replication and cell growth, to signalling and metabolism. So far, a systematic understanding of how both changes to the average as well as time-varying abundance of protein products can affect cellular processes and thus organismal fitness is missing. Investigating this problem is at is core fundamental science, as it is trying to address general mechanisms of how gene expression is regulated and has evolved. However, it is easy to see, how a better understanding of this problem also has translational aspects, such as in disease mechanisms or applications to synthetic biology (the engineering of organisms). The overall objectives are: - Quantifying how expression changes in many different genes affect organismal fitness - Generating insights into the core mechanisms of how gene expression changes affect fitness - Systematic classification of genes into groups with similar effect characteristics - Gaining insights into how the regulation of gene expression evolves
Data: CORDIS, © European Union
Project objective
Cellular and developmental processes rely on the precise activity of the proteins that constitute them, and alteration of protein activity often causes disease phenotypes and fitness defects. The relation between protein activity (or expression) and organismal fitness is thus a fundamental genetic property with implications for evolutionary and disease processes. However, a systematic understanding of how protein expression relates to fitness is lacking.Here we propose a comprehensive screen of expression-fitness functions (EFFs) for yeast genes.The proposed inter-disciplinary project will combine cutting-edge methods from synthetic biology, innovative one-step construction of a comprehensive genome-wide library, multiplexed genomics measurements and functional genomics computational analyses to elucidate fundamental patterns of expression-fitness functions.The methodology is based on an inducible degron system that allows for controlled repression of protein levels. Due to a one-fits-all design, the inducible degron can be fused in a one-step transformation procedure to any gene contained in the yeast GFP-fusion library. An all-in-one construction of the library, assessment of library components via deep-sequencing and multiplexed growth and expression assays will allow for the measurement of thousands of yeast gene EFFs in parallel.Computational data analyses will elucidate principal classes of EFFs. Subsequent functional genomics analyses will link principal EFFs to underlying molecular and physiological properties, such as gene’s functions, pathways or cellular localizations, which will therefore provide a foundation to understand the principal causes of how alterations in gene activity translate to impairments of cellular function.The proposed project will therefore open up a new area of systematic, quantitative genetic analysis that should prove crucial in the understanding of human genetic variation and disease.
Original text from CORDIS.
Participants
- FUNDACIO CENTRE DE REGULACIO GENOMICA · BarcelonaCoordinatorSpain
Links
Data: CORDIS, © European Union