Molecular Genetics - PhD and honours Projects - Role of a novel transcription factor in the regulation of early lung development
Role of a novel transcription factor in the regulation of early lung development
Project Type
PhD
Summary
Embryonic lung development is a beautifully choreographed process. Our laboratory recently discovered a novel transcription factor called ASCIZ that is essential for the earliest stages of lung development. ASCIZ knockout mice are able to specify respiratory progenitors in the foregut, but never even form lung buds and tracheal development also stalls at early stages. Probably as a consequence of the severe lung defect, these embryos also exhibit severe cardiac defects and die a few days before birth. The aim of this project is to characterize the detailed molecular mechanisms by which ASCIZ regulates early lung development. The project involves both advanced mouse genetic studies, including tissue-specific conditional deletion of ASCIZ during embryonic development, the identification of functionally relevant transcriptional targets, and biochemical and cell biological analysis of the signalling pathways involved.
Recent publication: Jurado et al, Dual Functions of ASCIZ in the DNA base damage response and pulmonary organogenesis, PLoS Genetics 6, e1001170 (2010); Heierhorst et al, A breathtaking phenotype – unexpected roles of the DNA base damage response protein ASCIZ as a key regulator of early lung development, Cell Cycle 10, 1222-24 (2011).