Waking up quiescent neural stem cells

Uncovering the transcription factor networks that control neural stem cell fate

Degree type

PhD

Closing date

1 June 2024

Campus

Hobart

Citizenship requirement

Domestic

About the research project

Neural stem cells are vital for the maintenance of the adult brain. However, for much of adult life neural stem cells are quiescent and do not generate new neurons.  Finding new means of reactivating quiescent neural stem cells (qNSCs) is a key therapeutic strategy to repair the ageing or damaged brain.  Although we know some extrinsic signals that can sometimes awaken and reactivate these cells (such as nutrition and exercise), we understand little about how gene transcriptional programs can switch between quiescent and reactivated cell fates.  This project aims to uncover the regulatory networks that control this switch in cell fate.

Amongst model organisms, the fruit fly (Drosophila melanogaster) is unique in having a well-defined developmental stage when all neural stem cells transiently become quiescent, making them easily profilable and manipulable. Drosophila qNSCs show all the hallmarks of mammalian qNSCs, responding to many of the same extrinsic reactivation cues and possessing the same characteristic morphology, making them an excellent model system for understanding neural stem cell biology and fate.

Transcription factors function in combinations to regulate gene expression and control cell fate, but the regulatory networks that control neural stem cell quiescence and reactivation are unknown. This project will use new modifications of the powerful Targeted DamID technique in Drosophila to rapidly profile the genome-wide binding of all expressed transcription factors in both active and quiescent neural stem cells. It will obtain new epigenetic and topological data and use these to develop three-dimensional models of the genome. Combining these datasets to define TF regulatory networks through epigenetics and topology, we will identify key transcriptional factors that control quiescence and activation.  Finally, we will validate these predictions via genetic manipulation to achieve the controlled, targeted reactivation of qNSC populations in the brain.

Primary Supervisor

Meet Dr Owen Marshall

Funding

Applicants will be considered for a Research Training Program (RTP) scholarship or Tasmania Graduate Research Scholarship (TGRS) which, if successful, provides:

  • a living allowance stipend of $32,192 per annum (2024 rate, indexed annually) for 3.5 years
  • a relocation allowance of up to $2,000
  • a tuition fees offset covering the cost of tuition fees for up to four years (domestic applicants only)

If successful, international applicants will receive a University of Tasmania Fees Offset for up to four years.

As part of the application process you may indicate if you do not wish to be considered for scholarship funding.

Other funding opportunities and fees

For further information regarding other scholarships on offer, and the various fees of undertaking a research degree, please visit our Scholarships and fees on research degrees page.

Eligibility

Applicants should review the Higher Degree by Research minimum entry requirements.

Ensure your eligibility for the scholarship round by referring to our Key Dates.

Additional eligibility criteria specific to this project/scholarship:

  • Applicants must be able to undertake the project on-campus

Selection Criteria

The project is competitively assessed and awarded.  Selection is based on academic merit and suitability to the project as determined by the College.

Additional essential selection criteria specific to this project:

  • Experience in molecular biology

Additional desirable selection criteria specific to this project:

  • Experience in Drosophila husbandry
  • Experience in genome-wide profiling of transcription factor binding (e.g. ChIP-seq, CUT&RUN, DamID or TaDa)
  • Experience with R coding and analysis
  • Experience with statistics / biostatistics / data analysis

Application process

  1. Select your project, and check that you meet the eligibility and selection criteria, including citizenship;
  2. Contact Dr Owen Marshall to discuss your suitability and the project's requirements; and
  3. In your application:
    • Copy and paste the title of the project from this advertisement into your application. If you don’t correctly do this your application may be rejected.
    • Submit a signed supervisory support form, a CV including contact details of 2 referees and your project research proposal.
  4. Apply prior to 1 June 2024.

Full details of the application process can be found under the 'How to apply' section of the Research Degrees website.

Following the closing date applications will be assessed within the College. Applicants should expect to receive notification of the outcome by email by the advertised outcome date.

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