Cells in multicellular organisms have specialized and unique identities that are characterized by the set of genes that they express. These cell 'types' and their gene expression signatures are stable, yet cells can also readily interconvert between different types when appropriate signals are received (for example, during wound healing stem cells differentiate and proliferate to repopulate a tissue).
Gene expression levels are determined by the proteins and RNAs that occupy the underlying DNA. Genes can be set into active and repressed states that tend to be maintained through multiple cell divisions, and thereby act as a cellular memory. We know a lot about how the different gene regulatory factors function individually to either maintain or switch gene expression states, or modulate expression levels, yet how these molecules work together to precisely orchestrate gene expression in a robust yet flexible and context-dependent manner remains unclear (1).
This project will focus on quantitative analysis of cellular memory mechanisms at the single cell level using high-throughput and live-cell imaging, genome editing, and molecular genomics assays. The successful applicant will study dynamics and variability of expression state-switching and quantitative regulation of model genetic loci in human induced pluriopotent stem cell (iPSC) differentiation as well as engineered synthetic loci in iPSCs. This will deepen our understanding of how cells control gene expression to enable both stability and plasticity.
Many developmental disorders and disease states such as cancer are underpinned by improper gene expression, and have been shown to critically depend on the conserved gene expression regulators that this project will focus on (for example, Polycomb repressive complexes). The findings of this fundamental research will therefore have strong relevance for our understanding of human health and diseases.
The Quantitative Single-Cell Gene Expression group:
Established October 2021, we are a relatively new group at Single Molecule Science, the EMBL Australia node at UNSW Sydney, based at the Lowy Cancer Research Centre. We are committed to building a diverse team to answer fundamental research questions and to providing a supportive and challenging training environment for students. Our group makes extensive use of high-throughput and high-content microscopy and automated image analysis, which enables detailed measurement of quantitative cellular phenotypes across large cell populations. These approaches are complemented by live-cell imaging of cell fate and transcription processes, acute perturbation experiments, and mathematical modelling. More details on our lab website.
Student opportunities and culture:
Our PhD students have access to advanced infrastructure, seminars and state-of-the-art facilities (sequencing, microscopy, flow cytometry), as well as to opportunities to visit and work with collaborators in Australia and abroad. Students will also have numerous opportunities to travel, present their work internationally, and to develop transferable skills that contribute to their career success, e.g. by attending the EMBL Australia PhD Course, and the EMBL Australia PhD symposium (organized by students for students). The Students of Single Molecule Science (SEAMS) network organizes social activities on a regular basis.
We are looking for passionate, dedicated and creative PhD candidates who are interested in challenging lab work and computational data analysis. You should have strong attention to detail and be a collaborative team player. Experience in cell biology, molecular biology, microscopy, image analysis or mathematical modelling is advantageous.
- Domestic applicants should have completed Honours (or equivalent), or expect to do so in 2022.
- International applicants should have completed a postgraduate qualification with at least one year research component (for example, MSc).
Successful competitive candidates will be provided a tax-free living stipend of AUD $28,854 per annum (RTP scholarship) and an additional top-up scholarship to the value of AUD $5,000 per annum.
How to apply:
Email the following to Dr. Scott Berry ([Email Address Removed]) before 3 September 2022:
- A cover letter with a brief statement of your suitability and motivation to apply,
- CV including contact details for referees,
- Academic transcripts (or a summary of final grades for recent studies) .
Start dates over the next 12 months negotiable.
More info: berrygroup.github.io, sms.unsw.edu.au