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PhD Project 2018: Investigating the biology of human tissue macrophages in health and disease

Apply here: https://www.findaphd.com/search/ProjectDetails.aspx?PJID=66609&LID=1238

Project Description

Macrophages, such as the microglia of the brain, play essential homeostatic, remodelling, recycling and defence functions in all the tissues of the body. When they are overwhelmed by specialized pathogens such as HIV-1, or chronic accumulations of debris such as amyloids, notably in neurodegenerative disease, their inflammatory response can result in serious tissue damage. In order to provide a physiologically authentic, yet genetically tractable model for the study of human tissue macrophages, we have developed a technology platform, based on human pluripotent stem cells, CRISPR/Cas9 gene editing and directed differentiation (Buchrieser, James et al. 2017, Haenseler, Sansom et al. 2017, Haenseler, Zambon et al. 2017). In this project, you will use these methods to investigate the function of defined candidate genes in these pathological processes.

Funding Notes

4 Year DPhil Prize Studentships cover University and College fees, a stipend of ~£16,500 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.

References

Buchrieser, J., W. James and M. D. Moore (2017). “Human Induced Pluripotent Stem Cell-Derived Macrophages Share Ontogeny with MYB-Independent Tissue-Resident Macrophages.” Stem Cell Reports 8(2): 334-345.
Haenseler, W., S. N. Sansom, J. Buchrieser, S. E. Newey, C. S. Moore, F. J. Nicholls, S. Chintawar, C. Schnell, J. P. Antel, N. D. Allen, M. Z. Cader, R. Wade-Martins, W. S. James and S. A. Cowley (2017). “A Highly Efficient Human Pluripotent Stem Cell Microglia Model Displays a Neuronal-Co-culture-Specific Expression Profile and Inflammatory Response.” Stem Cell Reports 8(6): 1727-1742.
Haenseler, W., F. Zambon, H. Lee, J. Vowles, F. Rinaldi, G. Duggal, H. Houlden, K. Gwinn, S. Wray, K. C. Luk, R. Wade-Martins, W. S. James and S. A. Cowley (2017). “Excess alpha-synuclein compromises phagocytosis in iPSC-derived macrophages.” Sci Rep 7(1): 9003.

Functional human artificial chromosomes are generated and stably maintained in human embryonic stem cells

Author(s):Mandegar, M.A. | Moralli, D. | Khoja, S. | Cowley, S. | Chan, D.Y. | Yusuf, M. | Mukherjee, S. | Blundell, M.P. | Volpi, E.V. | Thrasher, A.J. | James, W. | Monaco, Z.L.
Publication year: 2011
Journal / Book title: Human Molecular Genetics

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Source:: “james, william s.” 35479049300

Assessing similarity to primary tissue and cortical layer identity in induced pluripotent stem cell-derived cortical neurons through single-cell transcriptomics

Author(s):Handel, A.E. | Chintawar, S. | Lalic, T. | Whiteley, E. | Vowles, J. | Giustacchini, A. | Argoud, K. | Sopp, P. | Nakanishi, M. | Bowden, R. | Cowley, S. | Newey, S. | Akerman, C. | Ponting, C.P. | Cader, M.Z.
Publication year: 2016
Journal / Book title: Human Molecular Genetics

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Source:: cowley, sally a.” 7102482900 “james, william s.” 35479049300 “moore, michael d.

Excess α-synuclein compromises phagocytosis in iPSC-derived macrophages

Author(s):Haenseler, W. | Zambon, F. | Lee, H. | Vowles, J. | Rinaldi, F. | Duggal, G. | Houlden, H. | Gwinn, K. | Wray, S. | Luk, K.C. | Wade-Martins, R. | James, W.S. | Cowley, S.A.
Publication year: 2017
Journal / Book title: Scientific Reports

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Source:: cowley, sally a.” 7102482900 “james, william s.” 35479049300 “moore, michael d.

Efficient, Long Term Production of Monocyte-Derived Macrophages from Human Pluripotent Stem Cells under Partly-Defined and Fully-Defined Conditions

Author(s):van Wilgenburg, B. | Browne, C. | Vowles, J. | Cowley, S.A.
Publication year: 2013
Journal / Book title: PLoS ONE

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Source:: cowley, sally a.” 7102482900 “james, william s.” 35479049300 “moore, michael d.

CRISPR-mediated genotypic and phenotypic correction of a chronic granulomatous disease mutation in human iPS cells

Author(s):Flynn, R. | Grundmann, A. | Renz, P. | Hänseler, W. | James, W.S. | Cowley, S.A. | Moore, M.D.
Publication year: 2015
Journal / Book title: Experimental Hematology

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Source:: cowley, sally a.” 7102482900 “james, william s.” 35479049300 “moore, michael d.