Single cell live imaging in vivo, to understand cell activity in the context of regenerative medicine and cancer biology
Dr V See
Dr A Herrmann
Dr P A Murray
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
Stem cell-based, and more general cell therapies have shown promising results across many disciplines in medicine. However, several recent clinical studies have led to disappointing results, due to a lack of understanding of the fundamental mechanisms underpinning their effects. This project will monitor and track the interaction over time of multiple cell types transplanted in vivo and how they interact with the host tissues. We will use non-invasive cell imaging techniques to obtain real-time, quantitative, and long-term monitoring of transplanted cells and information on their migration, distribution, differentiation etc. We will use the chick embryo model either by direct injection of cells in the vasculature or organs or by exploiting the chorioallantoic membrane (CAM) model. CAM has the ability to support the growth and maintenance of live tissue/cells placed on its surface, making it an ideal bioreactor and a core resource to evaluate biological processes in regenerative medicine and cancer research. The chick embryo is not under home office regulation until Embryonic day14, thereby contributing to Replace/Reduce animal use. The limitation to date has been down to the lack of a labelling technology capable of transitioning from in vitro to in vivo. StreamBio has developed Conjugated Polymer Nanoparticles (CPNs™), which are highly stable, fluorescent labelling probes immensely brighter than conventional technologies, and have an iron oxide component for MRI contrast enhancing. Using the advanced imaging technologies at the University of Liverpool Centre for Preclinical Imaging -CPI- and Centre for Cell Imaging -CCI- for cellular and in vivo imaging; we will determine how neural undifferentiated/dedifferentiated cells interact with immune cells, the host tissue and vasculature, and how this environment impact on their identity in terms of differentiation, survival and migratory capabilities. The student will initially optimise the cell labelling capabilities of the CPNs in vitro; using classical 2D cell culture as well as 3D spheroid models with multiple cell types to mimic tissue organisation. They will then track neural stem cells and brain tumour cells labelled with the CPNs in the chick embryo, either live upon injection in the vasculature or long-term using the CAM assay and multimodal imaging. Importantly, we will also be able to track cell dissemination into the chick organs by using both the fluorescence and magnetic properties of the nanoprobes. Exploiting the multiplexing we will label both control cells and cells treated pharmacologically to obtain a mechanistic understanding of their differentiation and migratory properties in vivo.
HOW TO APPLY
Applications should be made by emailing [Email Address Removed] with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project and at the selected University. Applications not meeting these criteria will be rejected.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to [Email Address Removed]
Please note that the closing date for applications is Monday 18th May at 12noon.
This is a 4 year BBSRC CASE studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.
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Effects of hypoxic preconditioning on neuroblastoma tumour oxygenation and metabolic signature in a chick embryo model. Biosci Rep 38 (2018)
Non-invasive imaging reveals conditions that impact distribution and persistence of cells after in vivo administration. Stem Cell Res Ther 28;9(1):332. (2018)
Magnetic Resonance Imaging for Characterization of a Chick Embryo Model of Cancer Cell Metastases. Mol Imaging 2018, 17:1536012118809585 (2018)
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