The overall objective of the project is to better understand the fundamental principles of controllability of complex, biological networks, and how these control principles could be exploited to intervene in the network under analysis to change its dynamic behavior. The principles will be applied in two concrete case studies with important biotechnological and medical implications: (1) re-programming of prokaryote metabolism to enhance renewable and sustainable fuel production; and (2) finding druggable vulnerabilities of cancer networks for improved anticancer therapeutics.
The consortium represents a well-balanced network of complementary and multi-disciplinary skills. It incorporates and brings together scientists with expertise in four distinct fields: (1) Non-linear dynamical modeling of network behavior (Petre group), (2) Engineering prokaryotes for renewable fuel production (Jones group), (3) Network-based analyses of cancer drivers and synthetic lethality (Aittokallio group); and High-throughput RNAi and drug screening for personalized therapeutic strategies (Wennerberg group).
In particular, we will develop and demonstrate a new concept for guided metabolic engineering and targeted drug design that will have a considerable scientific impact in the field of synthetic biology, biomedicine and biotechnology in general. In the case of metabolism, the novel method to predict system drivers for global adjustment in biotechnological systems has many potential applications. Until now, rational metabolic engineering has been effectively a hit-and-miss process, even for targeted removal of competing reactions.
If such novel methods can be applied to efficiently predict engineering targets in the construction of catalytic strains for renewable fuel production, important progress is certain. From the cancer treatment point of view, if proved successful, this project will enable rational synthetic tailoring of the cancer networks using cancer cell’s own pathogenic features and other genetic vulnerabilities that can result in impressive selective therapeutic effects.
|Vladimir Rogojin||Diana-Elena Gratie, M.Sc.|
|Anne Seppänen||Li Chang|
Finnish Institute for Molecular Medicine (Tero Aittokallio, Krister Wenerberg)
Imperial College London (Patrik Jones)