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Regulatory signalling networks between stem and niche cells in lung regeneration. (360G-Wellcome-107633_Z_15_Z)

For multipotent stem cells to properly orchestrate injury repair, it is necessary for signals to instruct stem cells to produce specialised cells that replace injured epithelia. The precise signals from the stromal/niche cells that can stimulate differentiation for lung injury repair are under-investigated. In this proposal, I will directly address gaps in the understanding of the regulation of stem cell lineage differentiation by characterising novel stromal cell populations expressing Lgr6 in the murine distal lung and their functional interactions with region-specific stem cells during injury repair. Aim 1 will define dynamics of Lgr6-expressing cells by tracking them in homeostasis and during injury repair. In vitro organoid co-culture of regional epithelial stem/progenitor cells with Lgr6+ cells will address functional interactions between epithelia and Lgr6+ stromal cells. I will also determine if Lgr6+ cells are essential for stem cell lineage differentiation in vivo. Aim 2 will further dissect regulatory signalling molecules derived from Lgr6+ cells. Gene expression profiling of Lgr6+ cells with regional epithelial cells will describe key signalling pathways that will be evaluated by in vitro organoid co-culture assay and by in vivo mouse genetics. This work will enhance our understanding of regulatory networks between stem-niche interactions in lung regeneration.

£1,226,049

27 May 2015

Grant details
Amount Awarded 1226049
Applicant Surname Lee
Approval Committee Sir Henry Dale Fellowship Interview Committee
Award Date 2015-05-27T00:00:00+00:00
Financial Year 2014/15
Grant Programme: Title Sir Henry Dale Fellowship
Internal ID 107633/Z/15/Z
Lead Applicant Dr Joo-Hyeon Lee
Planned Dates: End Date 2020-06-30T00:00:00+00:00
Planned Dates: Start Date 2015-07-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Austin Smith
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