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
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.
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.
Applicants should review the Higher Degree by Research minimum entry requirements.
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)
After checking and ensuring that you meet the eligibility and selection criteria contact the project supervisor.