BIOSTAB-DIFF · Controlling cellular differentiation of industrial enzyme production in Bacillus subtilis

To cope with an ever changing environment, bacteria often develop a bet-hedging strategy like bi-stable cellular differentiation, resulting in cell populations with different properties. For example, the industrially relevant model bacterium Bacillus subtilis can become motile, genetically competent, secrete degradative enzymes, or sporulate, and these cellular differentiations can occur simultaneously in a single genetically homogenous population. This cellular heterogeneity exhibited by bacterial cells from the same parent with similar genetic properties is a carefully regulated process that prepares the population for unpredictable environmental stress. Unfortunately, this cellular differentiation can pose serious challenges for the production of enzymes via industrial fermentation, since it means that not all cells in the fermentor are actively involved in enzyme production. This Marie Curie BIOSTAB-DIFF project aims at investigating how enzyme expression differs between individual cells of B. subtilis, and how this cellular heterogeneity can be possibly controlled by genetic interventions. B. subtilis has become a universal microbial cell factory for many industrial products such as enzymes and vitamins. Better enzyme yield would be achieved by reducing cellular heterogeneity in this organism, and that would serve as an asset to the biotech industry. The project will be carried out in the Swammerdam Institute of Life Sciences (SILS) at the University of Amsterdam (UvA), under the supervision of Prof. Leendert Hamoen, one of the leading experts in heterogenic protein expression in the model organism B. subtilis.