Collagen assembly and accumulation in idiopathic pulmonary fibrosis. (360G-Wellcome-100638_Z_12_Z)
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease with significant unmet clinical needs. No therapy has been shown to improve a median survival of only 35 months. IPF is characterised by excessive proliferation of fibroblasts and their differentiation into myofibroblasts that produce large amounts of extracellular matrix (ECM) proteins including interstitial collagens. Although altered ECM cross-linking and stiffness at the cellular-scale are proposed to play a key role in t he mediation of IPF by promoting divergent myofibroblast behaviour, it is incompletely understood if, and at what scale, collagen assembly, accumulation, and biomechanical properties are altered in IPF. I hypothesise that aberrant collagen assembly and accumulation in IPF causes altered extracellular matrix physical properties and dynamics. This may promote the disease persistence and progression. Using cross-disciplinary collaboration, I propose to compare the ex vivo assembly and biome chanical properties of collagen in healthy and fibrotic lung tissue. I will then utilise a novel in vitro 3D primary human lung fibroblast culture model, and in vivo models, to examine the kinetics of collagen production and assembly in pulmonary fibrosis. Ultimately this work will increase understanding of ECM regulation in pulmonary fibrosis, and may aid in the identification of therapeutic targets.
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Grant Details
Amount Awarded | 219753 |
Applicant Surname | Jones |
Approval Committee | Clinical Interview Committee |
Award Date | 2013-02-20T00:00:00+00:00 |
Financial Year | 2012/13 |
Grant Programme: Title | Research Training Fellowship |
Internal ID | 100638/Z/12/Z |
Lead Applicant | Dr Mark Jones |
Partnership Value | 219753 |
Planned Dates: End Date | 2016-07-31T00:00:00+00:00 |
Planned Dates: Start Date | 2013-08-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South East |
Sponsor(s) | Prof Donna Davies |