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Exploring Parkinson’s related gene function in hiPS-macrophages and microglia

  • Full or part time
    Prof W S James
    Dr S Cowley
  • Application Deadline
    Friday, January 10, 2020
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

The macrophage is an evolutionarily ancient sentinel of the health of all of the body’s tissues: clearing away dead cells and debris; as brain-resident microglia, remodelling defunct neuronal connections; nurturing tissue stem cells; detecting and responding to pathogens. We have developed a genetically tractable system for differentiating authentic human tissue macrophages, especially microglia, from pluripotent stem cells, which is used widely to investigate disease pathogenesis and develop new therapies [1, 2]. Many Parkinson’s disease-associated genes are expressed in macrophages/microglia (notably LRRK2, a-synuclein, GBA, PINK1), and in the case of disease-associated variants, this leads to neuroinflammation [3, 4]. You will use human iPS cells to investigate the role of one of these genes in macrophage/microglia. Using the latest CRISPR/Cas9 technology to Knockout and/or introduce precise mutations, you will be able to dissect the molecular interactions and regulatory pathways through which these genes mediate immune dysfunction.

Funding Notes

4 Year DPhil Prize Studentships cover University fees, a tax free stipend of ~£17,009 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.


1. Haenseler, W., et al., A Highly Efficient Human Pluripotent Stem Cell Microglia Model Displays a Neuronal-Co-culture-Specific Expression Profile and Inflammatory Response. Stem cell reports, 2017. 8(6): p. 1727-1742.
2. van Wilgenburg, B., et al., Efficient, long term production of monocyte-derived macrophages from human pluripotent stem cells under partly-defined and fully-defined conditions. PloS one, 2013. 8(8): p. e71098.
3. Lee, H., W. James, and S. Cowley, LRRK2 in peripheral and central nervous system innate immunity: its link to Parkinson's disease. Biochemical Society transactions, 2017. 45(1): p. 131-139.
4. Lee, H., et al., LRRK2 is recruited to phagosomes and co-recruits Rab8 and Rab10 in human pluripotent stem cell-derived macrophages. bioRxiv, 2019: p. 779835.

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