Investigating transcriptional regulation of eosinophil development
Project type
Honours and/or PhD
| Supervisor(s) | Division | |
Dr Clare Morgan (Primary) |
Molecular Medicine | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Molecular Medicine | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Cancer and Haematology | .(JavaScript must be enabled to view this email address) |
Details of project
Blood cells play a central role in many diseases, from cancers, diabetes and arthritis to destructive inflammatory diseases, such as chronic obstructive pulmonary disease and asthma.
Our laboratory has conducted a detailed survey of gene expression in all blood cell types isolated at various stages in their development, from haemopoietic stem cells to mature, circulating cells. The scope and scale of this dataset, known as the HemAtlas, makes it a unique resource with which to identify genes associated with blood cell commitment, maturation and function.
One of our current interests is to understand the processes involved in eosinophil lineage commitment and differentiation. Eosinophils are a relatively scarce type of blood cell in healthy individuals, but are thought to play a pivotal role in many inflammatory diseases, including asthma and dermatitis. Using the HemAtlas, we have identified a number of transcription factors with an eosinophil-specific pattern of expression, suggesting that these genes may have a role in eosinophil production and regulation.
The aim of this project is to investigate the importance of one of these genes, Klf5, in haematopoiesis, and eosinophil development in particular, by studying a transgenic mouse model in which we can control Klf5 gene expression. You will use a range of cutting-edge molecular biology techniques, including RNAi and microarrays, to understand the effects of Klf5 expression at the transcriptional level. This project will also involve performing in vitro cell culture assays and in vivo transplantation experiments to investigate the role of Klf5 during blood cell development.
This project will be suited to both Honours and PhD candidates.
Project references
- Rothenberg, M.E. & Hogan, S.P. The eosinophil. Annu Rev Immunol. 2006;24,147-174. PMID: 16551246
- de Graaf CA, Kauppi M, Baldwin T, Hyland CD, Metcalf D, Willson TA, Carpinelli MR, Smyth GK, Alexander WS, Hilton DJ. Regulation of hematopoietic stem cells by their mature progeny. Proc Natl Acad Sci USA. 2010 Dec 14;107(50):21689-94. PMID: 2111581
Research interests
Our laboratory is interested in understanding the molecular regulation of cell proliferation and differentiation, with particular emphasis on the haematopoietic or blood cell-forming system.
Our current research program is focused on uncovering pathways regulating haematopoiesis, using a combination of forward and reverse mouse genetics, genomics, proteomics and bioinformatics.
In addition to our basic research, our laboratory is committed to developing clinical links and to applying our research through collaboration with the biopharmaceutical industry.
Selected publications
- Ng AP, Loughran SJ, Metcalf D, Hyland CD, de Graaf CA, Hu Y, Smyth GK, Hilton DJ, Kile BT, Alexander WS. Erg is required for self-renewal of hematopoietic stem cells during stress hematopoiesis in mice. Blood. 2011 Jun 14 [Epub ahead of print]. PMID: 21673349
- Taoudi S, Bee T, Hilton A, Knezevic K, Scott J, Willson TA, Collin C, Thomas T, Voss AK, Kile BT, Alexander WS, Pimanda JE, Hilton DJ. ERG dependence distinguishes developmental control of hematopoietic stem cell maintenance from hematopoietic specification. Genes Dev. 2011 Feb 1;25(3):251-62. PMID: 21245161
- Hilton DJ, Kile BT, Alexander WS. Mutational inhibition of c-Myb or p300 ameliorates treatment-induced thrombocytopenia. Blood. 2009 May 28;113(22):5599-604. PMID: 19252138
Research theme
Chronic inflammatory diseases
Scientific discipline
- Bioinformatics
- Cell Biology
- Genetics
- Genomics
- Molecular Biology
- Systems Biology
Keywords
Inflammation, eosinophils, transcription factor, blood cells