Design Unit

The design unit of the iLoop is primarily responsible for high-level strain design. For that purpose, the unit integrates physiological and systems-level data from the analytics and screening & fermentation units with computational models of the host organisms in order to predict genetic manipulations that are likely to increase product titer, yield, and productivity.

These high-level designs are then implemented further downstream by the genome engineering unit using different molecular techniques and combinatorial approaches.

The design unit’s function is carried out by the sequencing, informatics, and modeling (SIM) group at DTU Biosustain. Furthermore, the SIM group operates a next-generation sequencing facility, bioinformatics pipelines for high throughput data processing and statistical analysis, and builds a web-platform for data management and visualizations.

In addition to work in the iLoop, the SIM group also collaborates with the scientific sections on projects where the group’s key competences are needed.

Next-Generation Sequencing

The SIM group operates the in house next-generation sequencing (NGS) service for the iLoop and all other units at DTU Biosustain. The service includes library preparation and sequencing for microbial resequencing, RNA-seq, Tn-seq and amplicon sequencing. NGS is used extensively in conjunction of both platform and production strain development projects in the iLoop.

Bioinformatics

The SIM group performs data analysis and integration focusing on next-generation sequencing data for bacterial and yeast strains and CHO cell lines. We employ a standard toolbox of methods for variant calling and RNA-seq/Tn-seq data analysis. We also perform various custom analyses of amplicon sequencing data depending on the application. The group is also responsible for maintaining software tools such as the CRISPy CRISPR/Cas9 design site.

Software engineering

A major software engineering activity within the SIM group is the development of software infrastructure to collect and integrate experimental data from the different sections of the iLoop. This data is made accessible to iLoop scientists via an API as well as browser-based analysis and visualization tools, also developed within the group, with the goal of supporting better, more informed cell factory design decisions. A further role of software engineering is the development of tools to aid with the generation of robotic protocols from construct-level designs.

Modeling

The modeling part of SIM focuses on rational strain design:
● Omics and physiological data integration with models
● Predicting heterologous and native production pathways
● Estimation of maximum theoretical yields and production envelopes
● Over-expression, down-regulation, and gene knockout strategies

Modeling frameworks and tools we currently support are:
● Kinetic modeling of production pathways
● Genome-scale constraint-based modeling of metabolism and related processes
● Thermodynamic feasibility analysis of production pathways

Furthermore, we invest in method development:
● Kinetic modeling of central carbon metabolism
● Strain-specific genome-scale models of metabolism
● Modeling protein synthesis for enhanced protein expression

Modeling and strain design tools we develop:
cameo (a python library for computer assisted metabolic engineering and optimization)
MASS toolbox (a Mathematica package for kinetic modeling)

Contact

Nikolaus Sonnenschein
Senior Researcher
DTU Biosustain
+45 21 79 89 22

Contact

Lars Yannik Schöning
Senior Software Engineer
DTU Biosustain
+45 24 89 40 86

Contact

Lasse Ebdrup Pedersen
Senior Researcher
DTU Biosustain
+45 21 12 73 21
http://www.biosustain.dtu.dk/english/research1/iloop-core-unit/design-unit
23 SEPTEMBER 2017