GenoMik-Transfer

Research cluster: PROTumor / Subproject

Subproject 1: Development of E. coli mutants for save and efficient treatment of solid tumors

Project time: 01.02.10-30.04.13

Project leader:

Prof. Dr. Florian Gunzer, Technische UniversitÃ¤t Dresden

The TUD group is responsible for the coordination of the PROTumor consortium. This subproject, based on the established genome sequences of the aforementioned probiotic E. coli (Fig. 1), focuses on the construction of genetically modified E. coli strains for bacteriotherapy of solid tumors.

Therefor it is necessary to generate E. coli mutants with optimized expression of fluorescent proteins, particularly suited for intratumoral imaging. Based on these constructs, therapeutic strains with enhanced tumoricidal activity will then be developed. Another important approach of research is the establishment and evaluation of containment systems for recombinant therapeutic E. coli. Lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria, is well-known as major endotoxin of E. coli. To improve safety of E. coli based tumor drugs, LPS mutants will be developed by deleting genes encoding components of the LPS synthesis pathway. Similarly it is planned, to remove potential residual virulence and instability factors from the genomes of the used probiotic E. coli strains. Finally, the TUD group will maintain a website where the sequenced and annotated E. coli genomes are made available to the members of the consortium.