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Integrated evolutionary analyses of genetic and drug interaction networks in yeast

Objective

The ability of cellular systems to adapt to genetic and environmental perturbations is a fundamental but poorly understood process both at the molecular and evolutionary level. There are both physiological and evolutionary reasonings why mutations often have limited impact on cellular growth. First, perturbations that hit one target often have no effect on the overall performance of a complex system (such as metabolic networks), as perturbations can be adjusted by reorganizing fluxes in metabolic networks, or changing regulation and expression of genes. Second, due to the fast evolvability of microbes, the effect of a perturbation can readily be alleviated by the evolution of compensatory mutations at other sites of the network. Understanding the extent of intrinsic and evolved robustness in cellular systems demands integrated analyses that combine functional genomics and computational systems biology with microbial evolutionary experiments. In collaboration with several leading research teams in the field, we plan to investigate the following issues. First, we will ask how accurately genome-scale metabolic network models can predict the impact of genetic deletions and other non-heritable perturbations. Second, to understand how the impact of genetic and drug perturbations can be mitigated during evolution, we will pursue a large-scale lab evolutionary protocol, and compare the results with predictions of computational models. Our work may suggest avenues of research on the general rules of acquired drug resistance in microbes.

Field of science

  • /medical and health sciences/basic medicine/pharmacology and pharmacy/drug resistance
  • /natural sciences/biological sciences/genetics and heredity/mutation

Call for proposal

ERC-2007-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

SZEGEDI BIOLOGIAI KUTATOKOZPONT
Address
Temesvari Korut 62
6726 Szeged
Hungary
Activity type
Research Organisations
EU contribution
€ 1 280 000
Principal investigator
Csaba Pal (Dr.)
Administrative Contact
Gyorgy Posfai (Dr.)

Beneficiaries (1)

SZEGEDI BIOLOGIAI KUTATOKOZPONT
Hungary
EU contribution
€ 1 280 000
Address
Temesvari Korut 62
6726 Szeged
Activity type
Research Organisations
Principal investigator
Csaba Pal (Dr.)
Administrative Contact
Gyorgy Posfai (Dr.)