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  Neurodevelopment and neurodegeneration: CTP synthase and Cytoophidia in stem cells


   MRC Functional Genomics Unit

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  Dr J-L Liu  No more applications being accepted

About the Project

Our lab has discovered that CTP synthase is compartmentalized in a novel organelle, the cytoophidium (1, 2, 3). Moreover, cytoophidia are detectable in bacteria, yeast and mammals (review see 4). Compartmentation is essential for the localization of biological processes within a cell. CTP synthase has been an attractive target for developing agents against cancer, virus and parasites. The high conservation and widespread distribution of the cytoophidium among diverse organisms and cell types indicates that this novel compartment contributes to fundamental cellular processes.

Our long-term goal is to understand mechanisms of CTP compartmentation and the biology of the cytoophidium. We have discovered that cytoophidia are very abundant in neural stem cells (2). Further studies from our lab indicate that CTP synthase plays critical roles in neurodevelopment and malfunction of cytoophidia results in neurodegeneration. We will investigate the specific role of CTP synthase and cytoophidium in neuroal stem cells and how disfuction of cytoophidia contributes to neurodegeneration.

The specific aims of this project include:

• To investigate the importance of cytoophidia in the central nervous system (CNS).
• To study the role of cytoophidia in stem cells using Drosophila as a model.
• To understand the contribution of regulation and misregulation of cytoophidia during neurodevelopment and neurodegeneration.

Techniques and training will include RNAi screening, RNA-Seq, laser-scanning confocal microscopy, single-cell mutagenesis, metabolomics profiling, cellular and molecular biology, live imaging, developmental neuroscience and Drosophila genetics.

To apply, please send a copy of your CV, including names and contact details of two referees, and a covering letter indicating why you are interested in this project, to Miss Emily Frape at [Email Address Removed] or by post to the MRC Functional Genomics Unit, Department of Physiology, Anatomy & Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT.


Funding Notes

MRC studentships are only available to applicants who reside (or have residency) within the UK or EU. Students from outside the EU may also be considered for the project if they can secure their own studentship funding. Project start date October 2014.

Candidates must have, or expect to gain, a first or strong upper second class degree (or equivalent) in a relevant discipline. Successful candidates require acceptance by the University of Oxford so please refer to the University of Oxford Graduate Students pages for details of eligibility (http://www.ox.ac.uk/admissions/postgraduate_courses/apply/application_guide/).



References

1. Liu JL. (2010). Intracellular compartmentation of CTP synthase in Drosophila. Journal of Genetics and Genomics 37(5):281-96.
2. Chen K*, Zhang J*, Tastan ÖY*, Deussen ZA, Siswick MY and Liu JL. (2011). Glutamine analogs promote cytoophidium assembly in human and Drosophila cells. Journal of Genetics and Genomics (*These authors contributed equally to this work). doi:10.1016/j.jgg.2011.08.004. (cover story)
3. Azzam G and Liu JL. (2013). Only one isoform of Drosophila melanogaster CTP synthase forms the cytoophidium. PLOS Genetics 9(2): e1003256.
4. Liu JL. (2011). The enigmatic cytoophidium: compartmentation of CTP synthase via filament formation. BioEssays 33(3):159-64. (cover story)

For more information please visit the Liu Lab websites

http://groups.mrcfgu.ox.ac.uk/liu-group
http://dpag.medsci.ox.ac.uk/team/h-n/jilong-liu
http://www.mrcfgu.ox.ac.uk/research/ji-long-liu