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Understanding how mRNA export regulates stem cell potency

Project type

  • Honours
  • PhD

Project details

During embryonic development a single fertilised zygote gives rise to all the diverse cell types found in the adult body. Throughout this process and into adulthood, all cells in the body have largely the same DNA sequence, yet very different phenotypes. Our lab seeks to understand firstly how an identical DNA sequence can give rise to the wide range of cell phenotypes, but also shape how cells can respond and adapt.

The complement of genes which are active in any given cells is the primary determinant of phenotypic variation. The functional output of a gene involves much more than simply whether the gene is transcribed (i.e. turned on), and the complexity of this ‘post-transcriptional’ layer of regulation is only now being fully appreciated. Ultimately, for a transcript to serve as a template for protein synthesis it needs to find its way from the nucleus where its produced, to the cytoplasm where the active ribosomes reside. We hypothesise that this process of ‘nuclear export’ is an essential regulatory mechanism controlling productive gene expression in development, where tight control of dynamic gene expression is needed, and that certain cancer cells can alter their export dynamics to facilitate malignant growth. Our research aims to understand the principles of nuclear mRNA export using both developmental and cancer models with the ultimate goal of supporting fundamental and translational breakthroughs in biomedical research.

Projects are available to understand how mRNA export regulates embryonic stem cell potency and will be designed with the interests and expertise of the student in mind. Projects are predominantly wet-lab experimental with an option to also undertake bioinformatic analyses depending on the project and time frame. Our laboratory employs a range of techniques including cell culture, molecular cloning, gene editing, flow cytometry, microscopy, mRNA fluorescent in situ hybridisation (FISH), and bioinformatics. We also let the question being asked determine the most suitable techniques required and are thus always adopting new approaches.

About our research group

This discovery-project will be undertaken in the well-established Wickramasinghe laboratory which will be part of WEHI from November 2024 (see our recent paper, Ngo et al., Nature, 2024) and will be co-supervised by a senior postdoctoral fellow, Billy Hamilton (see Hamilton et al., Nature, 2020). This project will reveal new insights into how mRNA export regulates cell identity.

Education pathways