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GW4 BioMed MRC DTP studentship: Analysis of tissue remodelling and lipid metabolism in glioblastoma cancer stem cells using advanced chemically- and mechanically-sensitive optical microscopy


Project Description

Glioblastoma is the most common and most lethal adult brain cancer. High patient mortality is partly attributed to glioblastoma cancer stem cells causing recurrence of therapy-resistant tumours. Cancer stem cells are uniquely capable of propagating tumour growth, and recent work from our lab has shown that glioblastoma cancer stem cells preferentially metabolise lipids (Hoang-Minh et al. EMBO J 2018) and that they actively remodel their environment to access essential growth factors (Jimenez-Pascual et al. Cancer Discovery 2019). Tissue remodelling during invasion of glioblastoma cancer stem cells also results in the breakdown of myelin and the release of lipid droplets. Whether lipid droplets constitute an energy source for glioblastoma cancer stem cells remains unknown.
This project will resolve how glioblastoma cancer stem cells remodel their microenvironment and access lipid metabolites for energy support in live tissue and in real time. Combining two powerful optical microscopy techniques enables direct visualisation of biochemical and biomechanical changes in the environment surrounding glioblastoma cells. We will use Coherent Anti-Stokes Raman Scattering (CARS) microscopy to analyse the distribution of lipids in live cells and their surrounding tissue in time and space. CARS microscopy detects Raman-active vibrational frequencies of chemical bonds, coherently driven by the beat mode of two laser excitation beams interacting with the sample. This enables quantitative spatiotemporal profiling of biomolecules (lipids, proteins, nucleic acids) in live cells label-free with high spatial resolution (sub-micron) in 3D (DiNapoli et al. Anal Chem 2016).
Complementary to CARS, Brillouin Light Scattering (BLS) micro-spectroscopy is an emerging label-free biophotonics technique, which probes the micromechanical properties of tissues (such as the high-frequency elastic modulus and viscosity) through the frequency shift and linewidth of light scattered off thermally induced acoustic waves (Palombo et al. Analyst 2018). As the mechanical properties of tumours influence disease progression and malignancy, BLS microscopy provides a new approach to detect tumour rigidity on a similar spatial scale to the Raman probe. We will use BLS to determine how local micromechanical properties change during invasion and tissue remodelling of glioblastoma cancer stem cells.
This project will provide unprecedented molecular, chemical and mechanical imaging of the interactions between glioblastoma cancer stem cells and their microenvironment and how these create a permissive niche for tumour invasion and metabolic support. Blocking tissue remodelling may block access of glioblastoma cancer stem cells to essential nutrients and constitute a therapeutic strategy.

How to apply

Applicants must apply directly to the DTP as well as through the standard Cardiff University process: https://www.gw4biomed.ac.uk/doctoral-students/

To apply through the Cardiff University online application portal, please visit: https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/biosciences-phd-mphil-md

Funding Notes

This studentship is funded through GW4 BioMed MRC Doctoral Training Partnership. It consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£15,009 for 2019/20, updated each year) for 3.5 years, or the part-time equivalent.

Additional funding, known as the Research Training and Support Grant, of between £2,000 to £5,000 per annum (dependent on the research requirements of the project), is available over the course of the programme. This is to cover costs such as training, conferences and travel, and research consumables.

How good is research at Cardiff University in Biological Sciences?

FTE Category A staff submitted: 54.70

Research output data provided by the Research Excellence Framework (REF)

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