Descripció del projecte

The project “Rational design of Cutibacterium acne strains by non GMA techniques, for the use in skin microbiome modulation” is offered by Sbiomedics in colaboration with the translational synthetic biology group of Universitat Pompeu Fabra. Sbiomedics has the laboratories in the Jhonson & Jhonson facilities in Beerse, Belgium.

The human skin is not only a physical barrier composed by endogenous cells that protect our organism from pathogens invasion. It is also home for bacterial and fungal communities known as the skin microbiome.
The skin microbiome has a commensal relationship with the human skin cells, in which the microbiome provides extra protection to the skin against pathogens and helps in the education of our immune system. Nevertheless, physical damage on the skin or an unbalance in the skin microbiome can disturb the skin homeostasis and increase our susceptibility to acquire skin diseases.
Several bacteria species forming part of the skin microbiome have been identified, which distributions on the skin are very variable depending on the skin area that we look at due its different physiological properties. Moreover, bacteria community displacements have been described in some skin diseases and even some bacteria strains have been associated with skin diseases. Therefore, it is hypothesized that a rational modulation of the skin microbiome could potentially prevent and even cure some skin diseases.
In this project we aim to engineer Cutibacterium acnes, which is the main component of the facial skin microbiota. We will use for this engineering random mutagenesis and selection techniques. This type of strain improvement will result in natural organism not a genetically modified organism (GMO). The first approach is to randomly mutate C.acnes by using chemical or physical mutagens. This mutant library is then screened for knockouts of genes which have been described as virulence factors. We will start by selecting a knock out by random mutagenesis of the Christie-Atkins-Munch-Petersen (CAMP) factor, since it has been proved that its expression is involved in C.acnes induced inflammation. A haemolysis assay is already described to detect the presence of this factor. We therefore see it as a good starting point for the random mutagenesis. Once this knock-out is obtained, the next step will be to conduct a transposon library in C. acnes and obtain a list of all essential gene.
Finally, with the knowledge obtained out of the CAMP2 knockout assay and the transposon essential gene analysis, a pipeline will be developed in order to obtain all the mutants with the knock outs of interest.