Gene function in gut endoderm development
The aim of this project is to unravel the functions of newly identified genes in the development of the embryonic gut and the organs that derive from it.
This project addresses a fundamental issue of embryonic development at the start of life: the molecular activity controlling the formation of major body parts of the embryo. The epithelium of the primitive gut is formed from definitive endoderm and the muscle and connective tissues are mesoderm-derived. The foregut forms the liver, pancreas, the epithelium of the digestive tract and lungs, the thymus, thyroid and parathyroid glands. The molecular basis for the formation, organization and differentiation of these organs is not well understood, and this project is aimed at contributing to our knowledge of this process. As a first step towards this, we compared the genes expressed in the foregut endoderm of mouse embryos with tissues that do not contain endoderm using microarrays. From this analysis we identified a set of genes that are predominantly expressed in the endoderm and which do not, as yet, have any known function in early development. We are now using a variety of approaches to study the functions of some of these genes during development of the endoderm and its derivative organs. In this project, the effects of reduced or loss of gene function (by knockdown, gene-targeting or gene-trap) and gain of gene function (by electroporation, transfection and transgenesis) will be tested in mouse embryos, embryonic stem cells and other appropriate cell models.
In particular, we are investigating the function of the RNA binding protein RBM47. We recently published a work that demonstrates that RBM47 is involved in Cytidine to Uridine RNA editing, an unusual post-transcriptional modification. Our preliminary data show that it is also involved in the splicing of RNA. We generated transgenic mice that lack or overexpress Rbm47 and have developmental defects as a result. Current projects aim to combine iCLIP-seq and Mass-spectrometry to identify the ensemble of targets and partners of RBM47 and understand its role for the formation and the physiology of endoderm-derived organs.
Techniques and methodologies used in this project: genome analysis (RNA-seq, ChIP-Seq, iCLIP-Seq, single-cell transcriptome), protein analysis (mass-spectrometry, BioID, yeast two-hybrid), bioinformatics, genome editing (CRISPR-Cas9), 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, transfection, cell and embryo electroporation.
Eligibility: Honours entry: GPA on track for Hons I / IIA classification
PhD entry: Hons I classification, lab-based research experience is preferable.
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The opportunity ID for this research opportunity is: 1042
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