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Molecular analysis of cleft palate

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  • Full or part time
    Prof M Dixon
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Development of the lip and palate involves a complex series of highly integrated events that are frequently disrupted resulting in the congenital disoders cleft lip and cleft palate. Collectively, cleft lip and cleft palate have an estimated incidence of 1 in 500-2500 live births depending on geographic origin, racial and ethnic variation, and socio-economic status and result in considerable morbidity to affected families as individuals who exhibit this condition may experience problems with eating, speaking and hearing which can be corrected to varying degrees by surgery, dental treatment, speech therapy and psychosocial intervention. The frequent occurrence and significant burden imposed by cleft lip and cleft palate highlight the need to dissect the aetiology and molecular pathogenesis of this distressing condition.

Sonic hedgehog (Shh) has been shown to be a key regulator of palatal development. In this project, we will generate two high-throughput systems databases. First, we will determine Shh targets in the palatal mesenchyme by generating a highly filtered dataset. To enrich for direct Shh targets, we will compare palatal mesenchyme conditional Smoothened (Smo) loss- and gain-of-function microarrays and filter this dataset through a Gli Chromatin Immuno-Precipitation (ChIP) database. We will verify these targets in Smo mutant mice.

This project will therefore increase our understanding of the Shh signalling pathway during development of the secondary palate.

Funding Notes

This project has a Band 3 fee. Details of our different fee bands can be found on our website. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website. Informal enquiries may be made directly to the primary supervisor.

References

• Dixon MJ, Marazita ML, Beaty TH, Murray JC (2011) Cleft lip and palate: understanding genetic and environmental influences. Nature Reviews Genetics 12:167-178.

• Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC (2009) Cleft lip and palate. Lancet 374:1773-1785.

• Gritli-Linde A (2007) Molecular control of secondary palate development. Developmental Biology 301:309-326.

• Lan Y, Jiang R (2009) Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth. Development 136:1387-1396.

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