Dr V Li
No more applications being accepted
Funded PhD Project (Students Worldwide)
About the Project
This 4-year PhD studentship is offered in Dr Vivian Li’s Group based at the Francis Crick Institute (the Crick).
Adult tissue stem cells hold great promise for regenerative medicine strategies. Understanding the molecular mechanism of adult stem cell maintenance and differentiation is therefore important. Our lab use intestine as a model to study the regulation of stem cell lineage commitment, tumorigenesis and tissue regeneration. Intestinal stem cell (ISC) has been extensively characterised in the past decade after the identification of the stem cell marker Lgr5 (Barker N et. al., 2007). It is known that ISCs reside at the crypt bottom where Wnt signalling pathway is active (Li VS and Clevers H, 2012). Once leaving the stem cell niche, Notch signalling is crucial in regulating ISC binary fate decision between secretory (Notch off) and absorptive lineages (Notch on) (Philpott A abd Winton DJ, 2014). However, it remains still elusive of how Wnt and Notch signaling together maintain the stemness. Importantly, it is currently not undestood how the lateral inhibition of Notch signaling is established when ISC exits the stem cell niche, and if the bipotent progenitor exists for lineage commitment.
The project aims to characterise the regulatory mechanism of intestinal stem cell lineage commitment. Previous expression profiling analysis of intestinal stem cells and daughter cells in the lab has generated a handful of interesting candidate genes that potentially regulate ISC lineage commitment. To further characterise the functional roles of these candidates, we aim to generated knock-in (KI) reporter mice to perform lineage tracing experiments in vivo. We will also generate conditional knockout (KO) mice to study the loss of function phenotype in the intestine. We will employ the recent CRISPR/Cas9 genome editing technology for zygote targeting to generate KI and KO mice (Yoshimi K et. al., 2016). The result will help better understanding of the regulation of ISC lineage commitment, which may shield light on tissue regeneration and tumourigenesis.
Candidate with experience on tissue culture, mice handling or CRISPR/Cas9 gene editing will be advantageous.
Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2017 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).
Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.
APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE BY 12NOON GMT NOVEMBER 14TH 2016. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
https://www.crick.ac.uk/about-us/jobs-and-study/phd-programme/
Funding Notes
Successful applicants will be awarded a non-taxable annual stipend of £22,000 plus payment of university tuition fees. Students of all nationalities are eligible to apply.
References
1. Barker, N., J. H. van Es, J. Kuipers, P. Kujala, M. van den Born, M. Cozijnsen, A. Haegebarth, J. Korving, H. Begthel, P. J. Peters and H. Clevers (2007)
Identification of stem cells in small intestine and colon by marker gene Lgr5.
Nature 449: 1003-1007.
2. Li, V. S. W. and H. Clevers (2012)
In vitro expansion and transplantation of intestinal crypt stem cells.
Gastroenterology 143: 30-34.
3. Philpott, A. and D. J. Winton (2014)
Lineage selection and plasticity in the intestinal crypt.
Current Opinion in Cell Biology 31: 39-45.
4. Yoshimi, K., Y. Kunihiro, T. Kaneko, H. Nagahora, B. Voigt and T. Mashimo (2016)
ssODN-mediated knock-in with CRISPR-Cas for large genomic regions in zygotes.
Nature Communications 7: 10431.
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