SYBIL · Systems biology for the functional validation of genetic determinants of skeletal diseases

The aim of SYBIL is to carry out extensive functional validation of the genetic determinants of rare and common skeletal diseases and the age related factors contributing to these painful conditions. To achieve this goal SYBIL will gather complementary translational and transnational scientists, systems biologists, disease modellers, leading SMEs and industrialists that will perform in-depth characterisation (complete molecular phenotyping) of pre-clinical models (cellular and animal) for a variety of common and rare skeletal diseases. SYBIL will establish a systematic pipeline of in vitro, ex vivo and in vivo models of increasing complexity and will also make use of novel technologies such as iPS cells and exclusive ‘Virtual Patient’ software to identify potential therapeutic targets for further validation through simultaneous modelling of fundamental and complex physiological pathways. SYBIL will rely on i) an ‘Omics Knowledge Factory’ for systematically generating new knowledge on skeletal disease pathophysiology and to generate the relevant Omics profiles necessary to detect and validate new disease determinants, biomarkers and therapeutic targets for future clinical developments, and ii) a “Systems Biology Hub” to integrate the high-throughput and data-dense information, to gain a global understanding of pathophysiological commonalities between different skeletal diseases and recognize predominant shared pathways and mechanisms that may represent new targeted routes to treatment. SYBIL will also identify potential modifier genes and study the epigenome that will ultimately influence the timing and efficacy of new personalised treatments. Overall SYBIL achievements will tremendously boost the efficient pre-clinical assessment and development of therapeutics against skeletal diseases and thus indirectly reduce their social and healthcare burden.""