Analysing gene expression and blood cells

Using large-scale single cell RNAseq to dissect the genetic architecture of haematopoiesis and investigate implications for Bone Marrow Failure Syndrome and other complex diseases

Degree type

PhD

Closing date

29 October 2021

Campus

Hobart

Citizenship requirement

Domestic/International Onshore

About the research project

Bone marrow failure syndromes (BMFS) are a collection of heterogeneous disorders characterized by decreased production of one or more major hematopoietic lineages, which may be either inherited or acquired. BMFS is caused by inefficient haematopoiesis in the bone marrow (BM) stem cells, which means the number of red blood cells, white blood cells and platelets are insufficient to meet physiological needs. Approximately 160 Australians, the majority of whom are children or adolescents, are diagnosed with a BMFS each year. More than 50 percent of these patients will die from their disease. The outcome of these patients has greatly improved in recent years but is still poor for patients who lack a sibling donor and who failed or relapsed after immunosuppressive therapy.

Haematopoiesis involves the lineage-specification of blood cells, and is driven by context and cell-type specific gene expression. Variation in the expression of these genes that govern the differentiation and development of cell lineages directly alters production and activation of different blood cells. When regulation of this process goes awry, disease such as BMFS results. Since nearly all clinically measured hematopoietic traits exhibit extensive variation and are highly heritable, there is tremendous potential and excitement for the future of genetics and applications to understand human haematopoiesis.

We aim to understand the contribution of genetic variation in driving haematopoietic cell development, through dissecting the genetic drivers for haematopoiesis at a single cell resolution. This project will involve a mix of bioinformatics and wet lab work, initially working on the analysis of allelic effects on transcription changes from a cohort of niche BM samples that have already been collected. To functionally confirm our in silico findings we will design and perform CRISPR screens to model the effect of genetic variants on haematopoietic development and to understand the consequences.

Primary Supervisor

Meet Dr Kirsten Fairfax

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 $28,597 per annum (2021 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.

Eligibility

The project is open to domestic (Australian and New Zealand) and international applicants who are already in Australia (onshore) at the time of submitting their application.

Due to current Australian COVID-19 travel restrictions the University cannot accept applications from international applicants who are currently overseas.

Applicants should review the Higher Degree by Research minimum entry requirements and the following additional eligibility criteria specific to this project:

  • Applicants will need to be on campus (UTAS, Hobart, Medical Sciences Precinct) to conduct this PhD

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 desirable selection criteria specific to this project:

  • Basic bioinformatics skills (preferably some familiarity with R)

Application process

There is a three-step application process:

  1. Select the project, and check you meet the eligibility and selection criteria;
  2. Contact the Primary Supervisor, Dr Kirsten Fairfax, if you have any questions about the project; and
  3. Click here to submit an application by the closing date listed above.
    • 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.
    • As part of your application you will be required to submit a covering letter, a CV including contact details of two referees and your project research proposal.

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

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