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Developmental functions of a novel transcription factor

Developmental functions of a novel transcription factor

PhD/Honours project

Our laboratory discovered a novel transcription factor called ASCIZ that is essential for the earliest stages of lung development, and also for the survival of developing B cells in the bone marrow.  ASCIZ seems particularly important for the expression of the protein DYNLL1, which in turn may regulate the function of dozens of other proteins as a sequence-specific dimerizer.  The aim of this project is to characterize the detailed molecular mechanisms by which ASCIZ regulates the development of the lung, lymphocytes and other tissues and cell types.  The project involves 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.

Related publications: 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); Jurado et al, ATM substrate Chk2-ineracting Zn2+-finger (ASCIZ) is a bi-functional transcriptional activator and feedback sensor of dynein light chain (DYNLL1) expression, Journal of Biological Chemistry 287, 3156-64; Jurado et al, The Zinc-finger protein ASCIZ regulates B cell development via DYNLL1 and Bim. Journal of Experimental Medicine 209, advance-online-publication 13/08/2012.

Supervised by:

  • A/Prof Jörg Heierhorst
  • Disease Focus:

  • Cancer
  • Research Unit:

  • Molecular genetics