Head Development: Intersection of transcriptional and signalling activities
This project is designed to test the hypothesis that head formation during embryogenesis is controlled by a multitude of interacting transcriptional 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.
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 focuses on analysing the genetic and molecular activities that control the formation of a major body part, the embryonic head. 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 in the formation of the embryonic head and face. The experimental results will be collated for the construction of a gene regulatory network for head development in collaboration with the system biology laboratory at Monash University. The functional interaction between nodes and edges of the network will be tested in a system-based transcriptomic and proteomic approach in embryos generated from genome-edited embryonic stem cells using the CRISPR-Cas9 technology.
Opportunity available for both Honours and PhD students
Methodologies: Embryological analysis, genetic modification of cells and embryos (Cre/loxP, CRISPR-Cas9), cell and tissue culture, analyses of protein/gene expression (RNA-seq, mass spectrometry), molecular biology, immunohistochemistry, bioinformatics, system biology
Eligibility: Honours entry: GPA on track for Hons I / IIA classification
PhD entry: Hons I classification, lab-based research experience is preferable. 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. CMRI is supported in part by its key fundraiser Jeans for Genes®. 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.
Want to find out more?
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
The opportunity ID for this research opportunity is: 1043
Other opportunities with Professor Patrick Tam