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Marjan De Mey

Hometown: Ghent, Belgium.

Undergraduate Institution: Ghent University

Graduate Institution: Delft University of Technology, Ghent University, Massachusetts Institute of Technology

Project: Creation of molecular biological tools that enable fine-tuning of gene expression

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Creation of molecular biological tools that enable fine-tuning of gene expression

The dependence on limiting oil supplies is a factor prompting the chemical and biotechnological industries to explore nature’s richness in search of new ‘green’ technologies for the development of a sustainable bio-based economy. Industrial biotechnology uses biological systems for the production of useful compounds in the industry. One of the key technologies of industrial biotechnology is metabolic engineering which is the directed improvement of cellular properties through manipulation of enzymatic, transport and regulation functions of a cell using recombinant DNA technologies.

The traditional approach in metabolic pathway engineering of micro-organisms is to make an educated guess which modifications might improve or redirect the metabolic flux to a particular compound, in order to promote its overproduction. This approach is usually accompanied by a lot surprises. The complicated cellular network of metabolic fluxes and its regulation mechanisms is designed for adaptation to environment and to optimal replication. It is not designed to overproduce a particular compound. This leads to unexpected and counter-intuitive findings in practice.

Recently, this approach has been combined with new approaches to control gene expression, to modulate regulatory networks, to apply combinatorial genetics and/or to apply synthetic biology. Such a complementation of system genetic engineering with combinatorial techniques and random mutagenesis enables to further improve the micro-organisms and hence to obtain higher product yield. This is not always possible because these evolutionary techniques require high throughput screens, which are often not available for many desirable natural products. To overcome this screening problem multivariate-modular pathway engineering can be applied. In this approach the overall pathway is partitioned into smaller modules, and the modules’ expression are fine tuned by varying their expression simultaneously. In this way, the amount of combinations to be screened is reduced extensively.

These new advances in metabolic engineering emerge the need to develop new tools to fine tune genes through altering their expression. To this end it is important to elucidate the specific functioning of promoters and their regulation. Hence, the primary focus is to gather fundamental knowledge about the relation between the promoter structure, the gene expression level and the enzyme activity.