Collaboration in Systems and Synthetic biology of RTK Signalling

Brindle Lab in the Cell Signalling Group of the Department of Cardiovascular Sciences

Centre for Systems, Dynamics and Control at University of Exeter

participants: Deborah Alawo, Nick Brindle, Svetlana Amirova, Jongrae Kim, Declan Bates

acknowledgments: Medical Research Council

Synthetic Biology is a revolutionary new area of biological research that uses engineering design principles to build ("synthesize") novel biological functions and systems. Receptor tyrosine kinases (RTK) have essential roles in controlling cellular proliferation, migration, differentiation and gene expression, and defects in RTK signalling underlie numerous diseases, including cancer, heart disease and stroke. Cells receive multiple RTK and other signalling inputs and must integrate these to maintain normal cell functions and adapt to changes in the microenvironment. However, the underlying mechanisms of signal integration are still poorly understood. This project will use techniques from the new fields of Systems and Synthetic Biology to develop quantitative models of specific RTK regulatory mechanisms. Synthetic Biology approaches will be used to re-engineer these regulatory mechanisms in order to test and refine the models.

Possible applications: pharmacology; toxicology, therapeutic manipulation of signalling pathways relevant to ischaemic disease, inflammation and angiogenic pathologies.

Key references

  • B. N. Kholodenko, O. V. Demin, G. Moehren, and J. B. Hoek, Quantification of Short Term Signaling by the Epidermal Growth Factor Receptor, The journal of biological chemistry, 274, No. 42, pp. 30169-30181, 1999.

  • B. N. Kholodenko, Cell-signalling dynamics in time and space, Nature reviews, Molecular Cell Biology Volime 7, 2006, 165, pp.165-177.

  • W. W. Chen, B. Schoeberl, P. J. Jasper, M. Niepel1, U. B. Nielsen, D. A. Lauffenburger and P. K. Sorger, Input output behavior of ErbB signaling pathways as revealed by a mass action model trained against dynamic data, Molecular Systems Biology 5, 239, 2009

  • M.J. Plank, B.D. Sleeman, P.F. Jones, A mathematical model of tumour angiogenesis, regulated by vascular endothelial growth factor and the angiopoietins, Journal of Theoretical Biology 229 (2004) 435-454.

  • K. Bentley, G. Mariggi, H. Gerhardt, P. A. Bates, Tipping the Balance: Robustness of Tip Cell Selection, Migration and Fusion in Angiogenesis, PLoS Comput Biol 5(10), 2009



    Home