14-ERASynBio INTENSIFY

The INTENSIFY project will develop new technologies that combine highthroughput screening, next-generation sequencing and microfluidics to accelerate the discovery of biomolecules with novel and desriable functions. This technology will have manifold applications ranging from biotechnology to drug discovery.

The INTENSIFY project will develop a method for the rapid and comprehensive design of [i] system parts required for a novel functional design or [ii] a suitably comprehensive knowledge base to formulate a design model. The intensification is derived from the close integration in time and space of the determination of the sequence of an informational polymer (such as DNA) and its detailed functional characterization. To achieve this, we propose to implement the IODA-technology platform (Integration Of the Determination of DNA-sequence And function), in which we couple the available hardware infrastructure of next generation sequencing (NGS) with the in situ and in vitro characterization of the functions that are encoded by the DNA-molecule, either on the level of the informational polymer itself or at the protein level.
The use of the available NGS technology enables the design of highly parallelized and miniaturized assay scenarios. This allows including a previously "hidden dimension of screening" in the design considerations: Traditionally, insecurities in biosystem design were countered by the generation of libraries (many different biosystem variants) and the subsequent selection of only some of those variants that came close to the performance parameters for which the screening was specified. These variants were then sequenced in an effort to understand the result and then to extrapolate from a limited dataset for future design efforts. Now, with the novel scope of the screening process, the sequence of all variants (or at least a number that is orders of magnitudes higher than before) can be determined and the function characterized, so that the generated information is much more comprehensive, model formulation is broadly facilitated, and more parts become available for system design.

Our collaboration targets an application and will develop technologies of potential strategic importance for the pharmaceutical industry that could give rise to a host of novel applications and promises to deliver novel ways for the acceleration of the synthetic biology design process with potentially important consequences for the competitivity of European pharmaceutical industries in the face of aggressive competition from US and Asia in this area.