Metabolic cell biology: CTP synthase, Cytoophidia, Cancer and CRISPR
Supervisor: Dr Ji-Long Liu
Our lab has discovered that CTP synthase is compartmentalized in a novel organelle, the cytoophidium (1, 2). Moreover, cytoophidia are detectable in bacteria, yeast and mammals (review see 3). 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.
CTP synthase has been found upregulated in many types of cancer cells. CTP synthase has been an attractive target for developing agents against cancer, virus and parasites. Our long-term goal is to understand mechanisms of CTP compartmentalization within a cell. We will investigate how CTP synthase is assembled into the cytoophidium and how the cytoophidium is linked to cancer biology.
More recently, our lab has described a method for efficiently creating mutations in chosen Drosophila genes within a month based on the CRISPR/Cas9 system from bacteria (4). We will continue to develop and apply this cutting-edge genome engineering technology to generate multiple mutants for studying the biology of cytoophidia.
This project will address one of the following questions depending on the student’s interest.To study the role of cytoophidia in cancer biology.
- To characterize the ultrastructure and dynamics of cytoophidia.
- To determine the principal functions of cytoophidia.
- To search for factors regulating the biogenesis of cytoophidia.
- To apply CRISPR genome engineering technology to generate mutants to study cytoophidia.
Techniques and training will include CRISPR, RNAi screening, RNA-Seq, laser-scanning confocal microscopy, single-cell mutagenesis, metabolomics profiling, cellular and molecular biology, live imaging, developmental neuroscience and Drosophila and yeast genetics.
Funding: Applicants are expected to compete for local studentships
Contact details: Dr Ji-Long Liu
Applications by: 4th January 2013 https://apply.embark.com/grad/Oxford/16/
For more information please visit the Liu Lab website. http://groups.mrcfgu.ox.ac.uk/liu-group/contact-us
- Liu JL. (2010). Intracellular compartmentation of CTP synthase in Drosophila. Journal of Genetics and Genomics 37(5):281-96.
- Aughey G, Grice S, Shen QJ et al. (2014). Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism. Biology Open [Epub 17 Oct 2014]
- Liu JL. (2011). The enigmatic cytoophidium: compartmentation of CTP synthase via filament formation. BioEssays 33(3):159-64. (cover story)
- Bassett AR, Tibbit C, Ponting CP and Liu JL. (2013). Highly efficient targeted mutagenesis of Drosophila with the CRISPR/Cas9 system. Cell Reports 4(1):220-8.