Jan Roelof van der Meer
|Standarization and orthogonalization of the gene expression flow for robust engineering of NTN (new-to-nature) biological properties
Domaine: Cooperation FAB
Durée: 48 mois
Budget total: 5.998.735 EUR
Budget UNIL: 335.520 EUR
The ST-FLOW Project merges the efforts of 15 leading European and US research groups for developing material and computational standards that enable the forward-design of prokaryotic systems with a degree of robustness and predictability that is not possible with customary Genetic Engineering.
The central issue at stake is the identification and implementation of rules that allow the conversion of given biological parts assembled with a set of principles for physical composition into perfectly predictable functional properties of the resulting devices, modules and entire systems. ST-FLOW focuses on each of the steps that go from assembling a DNA sequence encoding all necessary expression signals in a prokaryotic host (by default, E. coli) all the way to the making of the final product or to the behaviour of single cells and populations.
Two complementary approaches will be adopted to solve the conundrum of physical composition vs. biological functionality of thereby engineered devices. In one case (bottom up), large combinatorial libraries of gene expression signals will be merged with suitable reporter systems and the input/output functions examined and parameterized in a high-throughput fashion. The expected outcome of this effort is to establish experience-based but still reliable rules and criteria for the assembly of new devices and systems -following the same physical composition rules or adopting CAD design. Yet, many outliers (combinations that do not follow the rules) are expected, and making sense of them will be the task of the complementary top-down approach.
In this case, ST-FLOW will revisit some of gaps in our knowledge of the gene expression flow (transcription, mRNA fate, translation) that need to be addressed for engineering functional devices from first principles. Ethical, legal and societal issues will also be examined in a context of public dialogue and sound science communication.