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Characterisation of a 3-dimensional organoid platform as a model for the study of liver cell plasticity in human cholangiocarcinoma

   College of Medicine and Veterinary Medicine

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  Dr L Boulter, Dr Rachel Guest  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

This is an opportunity to undertake doctoral research at the Edinburgh Cancer Research Centre (ECRC), part of the Institute for Genetics and Cancer (IGC) at the University of Edinburgh. We are looking for an enthusiastic, ambitious and self-motivated researcher to join our team and undertake a substantive research project leading to a PhD. The candidate will be encouraged to develop non-technical attributes that will equip them for a career in biomedical research, including the ability to work within teams, foster collaboration and networks, and to develop goal-setting and planning skills. Research integrity and a healthy research environment will be placed at the forefront of their experience and they will be encouraged to participate, where appropriate, in public engagement and science communication initiatives. We intend that the successful candidate will present their work at national and/or international forums and contribute to the open culture of the centre by participating in lab meetings and ‘work in progress’ seminars. We are a vibrant and inclusive laboratory where scientists and clinicians work side by side to bring together clinical expertise and cutting-edge science with the goal of better understanding the molecular mechanisms underpinning primary liver cancer and bring tangible benefits to patients. 

Cholangiocarcinoma (cancer of the bile ducts) is a highly aggressive, frequently fatal primary liver cancer with currently very few treatment options for patients. The incidence of this cancer has been increasing across the UK and especially in Scotland. Historically cholangiocarcinoma has been poorly studied with little dedicated research, however in recently the application of next generation sequencing to these tumours has opened up exciting avenues for new research and treatment. Our lab is interested in how the plasticity of the liver and its potential for regeneration might contribute to primary liver carcinogenesis. 

This project aims to evaluate the utility of 3-dimensional organoid culture systems for modelling liver cell plasticity. In particular, we are interested in hepatocyte to biliary cell fate transitioning as a contributing mechanism to biliary carcinogenesis. The student will use human livers unsuitable for clinical transplantation and transgenically labelled mouse livers to derive and maintain 3-dimensional hepatocyte and biliary organoids in culture. In the first year of the project the candidate will characterise these systems to establish phenotype, functionality, stability in culture and potential for expansion. The student will gain experience in a range of techniques in use in the ECRC including transcriptomic and proteomic assessment using targeted RNA-seq and mass spectrometry. They will gain expertise in flow cytometry and cell sorting as well as having access to high resolution imaging systems such as Opretta confocal microscopy and live cell imaging. Some prior experience in basic tissue culture techniques is of benefit but not essential. In the second and third years of the project the student will engineer and optimise a number of gene editing systems including CRISPR/Cas9 to test candidate genetic drivers of liver cell identity and assess the utility of certain genes for identity transitioning between liver cell types.  

Applicants should hold at least an upper second-class degree in a relevant subject and comply with English language requirements (

Applicants should send a covering letter, stating why they are interested in applying for the project, as well as an up-to-date CV and 2 academic references by Friday 4th March to Dr Rachel Guest ([Email Address Removed])

Proposed start date of studentship is 1st May 2022.

What is included:

-         Tuition fees for UK/International candidates

-         £8,000 per year consumable budget (capped)

-         Yearly stipend for 3 years (approx. £15,000)

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