The JAK-STAT signalling pathway is critical for propagation of signals from the engagement of cytokines with receptors on the surface of blood cells to transcription of genes in the nucleus. A key player in erythroid cell and platelet production is JAK2 which acts downstream of the Epo Receptor and Tpo Receptor (MPL). Mutations in JAK2 are very common in humans and result in a group of chronic blood cell cancers known as the myeloproliferative neoplasms (MPNs). STAT5, a transcription factor which is held in a quiescent state in the cytoplasm, is phosphorylated by JAK2. This results in translocation to the nucleus, binding to specific DNA motifs known as GAS elements, and gene activation. Up until recently we understood very little about the direct targets of STAT5 in the nucleus but the Cancer genomics (Perkins) group have recently performed the first successful ChIP-seq experiment for STAT5 in mouse blood progenitor cells. This project with examine the function of new STAT5 target genes in human blood cells. The project's hypothesis: New JAK2-STAT5 target genes will be useful biomarkers of disease in MPNs and will provide new insights into how the pathway controls blood cell production after physiological stressors. The student will undertake RNA-seq in the human erythroid cell line, HuDEP2, after stimulation with EPO to determine EPO-responsive genes. The student will also undertake ChIP-seq for pSTAT5 in the same cells. Analysis of the data will be undertaken in comparison with recent similar data generated in mouse cells. The student will also validate upregulation of certain target genes in clinical samples form patients with MPNs to determine whether they are valuable biomarkers of disease and its treatment. Techniques: Cell culture, FACS, QRT-PCR, RNA-seq, ChIP-seq, bioinformatics, translational research.
Transcription, JAK2, blood cancer, STAT5, cell, gene, biomarker, RNA-seq, cell culture, FACS, PCR, bioinformatics, translational research
Central Clinical School » Australian Centre for Blood Diseases (ACBD)
Masters by research
Masters by coursework
Australian Centre for Blood Diseases