Head Development: Intersection of transcriptional and signalling activities

Summary

This project is designed to test the hypothesis that head formation during embryogenesis is controlled by a multitude of interacting transcription and signalling activities and that severe phenotypic consequence of the perturbation of these activities will place them at the critical intersection for directing cell differentiation and tissue patterning.

Supervisor(s)

Professor Patrick Tam, Dr Nicolas Fossat

Research Location

Westmead - Childrens Medical Research Institute

Program Type

PHD

Synopsis

In humans, lethal malformation complexes of the head are associated with varying degrees of anatomical defects of the brain, skull and face structures. Congenital malformations of the brain ranging from reduction in size (microcephaly), abnormal partitioning (holoprosencephaly, rhinencephaly) to the severe loss of tissues (anencephaly) has increased to 7.6 per 10,000 birth in 2002-3. In addition, 1.6 per 10,000 births displayed developmental defects of oro-facial structures. It is believed that these major anatomical defects of the craniofacial structures result primarily from abnormal morphogenesis in the first trimester of human development. This coincides with the time window of head formation, 7-11 days after conception in the mouse embryo, which is utilized as an experimental model for analysing the genetic and developmental mechanisms of the pathogenesis of the human malformations.  This project addresses a fundamental issue in embryonic development: the genetic and molecular activities that control the formation of a major body part. Specifically, this study will utilize genetic and embryological models in which transcription factor coding genes are ablated in a tissue-specific manner to study how their loss in specific types of progenitor cells may impact on the severity of head malformation. We will also analyze the connection of these transcription factors with WNT signalling activity that, in conjunction, influences tissue differentiation and morphogenetic movement, and elucidate the functional interaction of these transcription factors and WNT signalling controlled downstream genes in the formation of the embryonic head and face.

Additional Information

Opportunity available for both Honours and PhD students 

Methodologies:  Embryological analysis, Genetic modification of cells and embryos, Cell and tissue culture, Cell and molecular biological analyses of protein/gene expression, Molecular Biology, Immunohistochemistry.  

Eligibility: Honours entry: GPA on track for Hons I / IIA classification              
              PhD entry: Hons I classification, lab-based research experience would be preferable.

The Children’s Medical Research Institute (CMRI) is an award-winning state-of-the-art medical research facility, with over 100 full-time scientists dedicated to researching the genes and proteins important for health and human development. The CMRI is supported in part by its key fundraiser Jeans for Genes®. Our scientists are internationally recognised research leaders and foster excellence in postgraduate training. CMRI graduates are highly sought after nationally and internationally. CMRI is located at Westmead, a major hub for research and medicine in NSW, and is affiliated with the University of Sydney. Easy to access by public transport. Projects are multi-disciplinary with training in molecular and cellular biology techniques, with some involving mass spectrometry, proteomics, protein-protein interactions, transgenic animals or live cell imaging. We are looking for top quality students who can prove a dedicated interest and enthusiasm for scientific research.

Candidates may apply for a CMRI PhD scholarship, which exceeds the Australian Postgraduate Awards and NHMRC scholarships in value; visit the CMRI website for details.

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Keywords

embryology, molecular biology, mouse, signalling activity, transcription factor, head, brain, embryonic stem cells, Progenitor cells, Cell Differentiation, developmental genetics, gene expression, gene targeting, knock-out, knock-down, RNA, siRNA

Opportunity ID

The opportunity ID for this research opportunity is: 1043

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