Systems Biology of Genetic Diseases: Elucidating Gene Function and Drug Mode of Action

A cell can be described as a synergistic ensemble of biological entities (mRNA, proteins, ncRNA, metabolites, etc) interacting with each other, whose collective behaviour causes the observed phenotypes. Massive amount of data have been, and are being, collected from laboratories worldwide using a variety of high-throughput experimental techniques to map physical and regulatory interactions in mammalian cells. The objective of this project is to develop and apply Systems Biology approaches to gain a systems-level understanding of gene regulation at the transcriptional, post-transcriptional and post-translational level in specific tissues, and to relate regulation to metabolic function. Gene regulatory networks will be computationally reconstructed from heterogeneous large-scale experimental data. We will then reconstruct a gene regulatory network describing regulatory interactions occurring in the human retina. Such a network will be instrumental to identify previously unknown regulatory mechanisms, which could have an impact on understanding and treating retinopathies. We will also reconstruct a model of gene regulation and metabolism in human and mouse liver. The model will be used to explore pharmacological treatments of inborn error of metabolism with a specific focus on Primary Hyperoxaluria Type 1 (PH1).