Team:UPMC PARIS/Description
OVERVIEW
Realizing that the lack of access to health care is a major problem in developing countries, we decided to create an automated user-friendly mobile factory able to produce therapeutic molecules for multiple diseases.
With our project “The BioMaker Factory”, we have rethought the way in which the drugs based on the latest advances in biological engineering and engineering are produced. Thus, we propose a small portable factory whose bioproduction of therapeutic molecules is fully automated by specific software and allows specific doses of the raw elements of therapeutic drugs to be delivered on demand. Local need-based production using the factory would, therefore, reduce the production and conservation costs of medications.
The tool would be provided to humanitarian workers, local institutions and health care facilities, enabling them to significantly improve access to health care for the concerned populations. The biological background of “The BioMaker Factory” gives it great modularity and an important capacity to produce many different molecules. From immunotherapies to food supplements. “The BioMaker Factory” has a potentially unlimited range of applications that we want to make available to as many people as possible.
But how does “The BioMaker Factory” work in general? After choosing the necessary treatment based on the local demand, the integrated computer automatically selects the strain of bacteria that develops through a smart bioreactor. A true miniature laboratory capable of producing proteins and other molecules such as anti-inflammatories or vitamins to treat diseases. The objective of the biological axis of “The BioMaker Factory” project was to develop an efficient and scalable tool for the bioproduction of large quantities of biologically active therapeutic molecules. To do so, we opted for a bacterial host, Escherichia coli, for its rapid growth and maneuverability.
For designing our model, we had three objectives to fulfill: 1. First we chose to work on a strain optimized for the production of eukaryotic proteins; Rosetta Gami® E. coli. In this strain, the trxB/gor mutation increases the oxidoreduction potential of the bacterial cytoplasm which allow the formation of disulfide bounds. In addition, it carries plasmids that suppliy seven rare tRNAs to alleviate codon bias. 2. Second, we chose to co-express therapeutic proteins with a cytosolic form of a chaperone naturally present in E. coli and effective on a broad spectrum of heterologous proteins, Skp (Seventeen Kilodalton Protein) (BBa_K254000). On the other hand, we planned to control very precisely the production of the protein of interest through optogenetic tools. This is to increase the yield by triggering the expression of the proteins at the best time for the bacteria without adding toxic additives in the culture medium. 3. Finally, our main objective was to develop a modular tool easily adaptable to the needs presented locally. We have therefore made an overall optimization of the Rosetta Gami strain for a wide range of eukaryotic proteins. So that these optimizations are stable and durable even in the absence of selection antibiotics, we integrated the different elements directly into the bacterial genome at different sites.
