Systems biology is a new and rapidly growing discipline. It is widely believed to have a broad transformative potential on both basic and applied studies in the life sciences. In particular, metabolic network reconstructions are playing a key role as they provide a framework for investigation of the mechanism underlying the genotype-phenotype relationship. Pseudomonas aeruginosa is an opportunistic pathogen of clinical relevance with an increasing resistance against available antibiotics, which is partially attributed to its ability to form biofilms. The proposed project will construct a comprehensive biofilm model of P. aeruginosa using a recently published metabolic reconstruction. The biofilm model will represent typical micro-habitats. Hence, it will give insight into distinct metabolic difference of planktonic and biofilm-associated bacteria and may further our understanding as to why biofilm bacteria are resistant to antibiotics. Metabolomic, patient samples will be integrated with the biofilm model which is expected to yield insight into conditions associated with disease progression and manifestation. The biofilm model will also be employed to predict new strategies for therapeutic interventions through in silico gene deletion studies. The project will include the development of relevant reconstruction and analysis methods. This work will set new standards in reconstruction, analysis, and modeling techniques and will build the first large-scale bacterial-community-based network. Gained knowledge will be directly applicable to other single or multi-species bacterial communities. The proposed project will be carried out within the Center for Systems Biology at the University of Iceland. Lastly, the project is well placed within the recent European efforts to apply systems biological approaches towards improving early diagnosis and accelerating the discovery of novel interventions.
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