Embryology Unit Children's Medical Research Institute

Lab head: Professor Patrick Tam
Location: Children's Medical Research Institute

This project explores the cellular and molecular mechanism of the establishment of the body plan and the formation of organs during embryonic development and elucidates how faults in the morphogenetic process disrupts development using genetic models of birth defects and embryo-derived stem cells.

Website: http://www.cmri.org.au/Research/Research-Units/Embryology
Lab members: Dr Nicolas Fossat
Funding: NHMRC
Research approach equipment: Genome analysis (RNA-seq, ChIP-Seq, iCLIP-Seq, ChIP-nexus, microfluidic qPCR and single-cell transcriptome), protein analysis (mass-spectrometry, BioID, yeast two-hybrid), bioinformatics, system biology, genome editing (CRISPR-Cas9, Piggy-Bac transposase, Cre-loxP system), dissection and manipulation of mouse embryos, molecular biological methods for gene cloning and analysis of gene expression (including real-time PCR and in situ hybridization), histology, immunofluorescence, cell culture, generation of organoids, transfection, organoids, cell and embryo electroporation.
Publications:

Head Development: Intersection of transcriptional and signalling activities

Primary supervisor: Patrick Tam

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.


Discipline: Applied Medical Sciences, Westmead
Co-supervisors: Nicolas Fossat
Keywords: Molecular biology, Bioinformatics, Genetics
Contact: