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Decoding Context-Dependent Genetic Networks in vivo

Objective

The evolutionary success of multicellular organisms is based on the division of labor between cells. While some of the molecular determinants for cell fate specification have been identified, a fundamental understanding of which genetic activities are required in each cell of a developing tissue is still outstanding. The DECODE project will develop and apply leading-edge system genetics methods to Arabidopsis and Drosophila, two major model systems from the plant and animal kingdoms to decode context-dependent genetic networks in vivo. To achieve this, DECODE will bring together experimental and theoretical groups with complementary expertise in model organism genetics and cellular phenotyping, single-cell genomics, statistics and computational biology. Building on our combined expertise, we will create functional genetic maps using conditional CRISPR/Cas9-based single- and higher order knockout perturbations in vivo combined with single-cell expression profiling and imaging. Coupled with powerful computational analysis, this project will not only define, predict and rigorously test the unique genetic repertoire of each cell, but also unravel how genetic networks adapt their topology and function across cell types and external stimuli. With more than thousand conditional knockouts, characterized by several million single-cell transcriptome profiles and high-resolution imaging this project will create the largest single-cell perturbation map in any model organism and will provide fundamental insights into the genetic architecture of complex tissues. Analyzing two tissues with divergent organization and regulatory repertoire will enable us to uncover general principles in the genetic circuits controlling context
dependent cell behavior. Consequently, we expect that the DECODE project in model organisms will lay the conceptual and methodological foundation for perturbation-based functional atlases in other tissues or species.

Field of science

  • /natural sciences/biological sciences/genetics and heredity
  • /natural sciences/mathematics/pure mathematics/topology

Call for proposal

ERC-2018-SyG
See other projects for this call

Funding Scheme

ERC-SyG - Synergy grant

Host institution

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Address
Im Neuenheimer Feld 280
69120 Heidelberg
Germany
Activity type
Research Organisations
EU contribution
€ 4 042 500

Beneficiaries (3)

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Germany
EU contribution
€ 4 042 500
Address
Im Neuenheimer Feld 280
69120 Heidelberg
Activity type
Research Organisations
RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Germany
EU contribution
€ 2 812 500
Address
Seminarstrasse 2
69117 Heidelberg
Activity type
Higher or Secondary Education Establishments
EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany
EU contribution
€ 3 770 000
Address
Meyerhofstrasse 1
69117 Heidelberg
Activity type
Research Organisations