Objetivo While conventionally effects of a chemical structure on a biological system have been determined for individual compounds, one at a time, it is now becoming apparent that biological effects of compound combination are not additive, but often conditional (antagonistic or synergistic) in nature. This phenomenon is of relevance both in the medicinal context (where drugs can be combined to have a synergistic effect), as well as the area of toxicology (where the simultaneous application of compounds shows a toxicity that is non-additive). However, it is not yet clear how to model, and anticipate, which compound combinations show this type of effect.Hence, in this work I will derive models of synergistic compound combinations, which will be prospectively validated in experiments. Furthermore, I will describe how to capture the effect of a chemical structure on a biological system on multiple levels, namely by considering structural features of the compound, its bioactivity profile, and pathway annotations and their relationship to the phenotypic effect observed. By integrating the data generated in a biologically meaningful way, this allows us to generate predictive models for the bioactivity of compound combinations. The relevance of this work ranges from the question which drugs can be combined in a synergistic manner and which combinations should rather be avoided to the safety assessment of chemicals. Hence, with this work I will be able to improve upon the current state-of-the-art in bioactivity data integration and modelling approaches, as well as deliver concrete models for the bioactivity assessment of compound combinations. Ámbito científico medical and health sciencesbasic medicinetoxicology Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Convocatoria de propuestas ERC-2013-StG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Aportación de la UE € 1 499 558,00 Dirección TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Reino Unido Ver en el mapa Región East of England East Anglia Cambridgeshire CC Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Renata Schaeffer (Ms.) Investigador principal Andreas Bender (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Reino Unido Aportación de la UE € 1 499 558,00 Dirección TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Ver en el mapa Región East of England East Anglia Cambridgeshire CC Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Renata Schaeffer (Ms.) Investigador principal Andreas Bender (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
