A combined in vitro and in virtuo multi-scale approach to understanding calcium signalling as a signature and integrator of cellular response. (360G-Wellcome-090577_Z_09_Z)
An integrated process of computational model development, quantitative experimentation and iterative cycles of simulation and hypothesis testing will be used to characterise calcium signals generated during epithelial scratch-wounding and explore how these are translated into individual cell response and emergent tissue behaviour. Calcium-signalling and cell response will be monitored in scratch wounded uro-epithelial cell cultures. Candidate receptor and ion channel expression will be inferred from pre-existing transcriptome data and confirmed functionally using agonists/inhibitors. These data will be used to inform modules of a computational model incorporating different mechanisms of calcium release and signal transmission. The calcium signature (amplitude and duration) experienced in response to a specific stimulus will be mapped to the resultant cell response and used to inform a software agent model that will be used to explore wound healing as an emergent context-specific prop erty of individual cell response. The key goals are 1) Characterisation of calcium signalling mechanisms during urothelial self-repair. 2) Integrate calcium signalling with individual cell response in a nondeterministic agent-based computational model in order to investigate emergent field properties. 3) Develop an extensible computational tool for biologists to relate calcium signalling and cell behaviour in different tissues and situations, such as compromised wound healing.
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Grant Details
| Amount Awarded | 371918 |
| Applicant Surname | Southgate |
| Approval Committee | Molecules, Genes and Cells Funding Committee |
| Award Date | 2010-02-04T00:00:00+00:00 |
| Financial Year | 2009/10 |
| Grant Programme: Title | Project Grant |
| Internal ID | 090577/Z/09/Z |
| Lead Applicant | Prof Jennifer Southgate |
| Other Applicant(s) | Dr Dawn Walker |
| Partnership Value | 371918 |
| Planned Dates: End Date | 2013-08-31T00:00:00+00:00 |
| Planned Dates: Start Date | 2010-09-01T00:00:00+00:00 |
| Recipient Org: Country | United Kingdom |
| Region | Yorkshire and the Humber |