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The Physics of Cancer: fundamental studies of cancer spheroids.


Project Description

Fundamental studies of cancer spheroids.

Background: Two dimensional (2D) cell cultures of cancer cells have been used to study their biology for decades. However such 2D studies only provide limited information since they fail to reproduce important aspects of the 3D tumour microenvironment, such as complex cell-cell interactions, the development of blood vessels and complex changes in chemical gradients such as the diffusion into the tumour of glucose and oxygen.

This project is a collaboration between Prof Weightman’s research group in the physics department [1-7] and Prof Sarah Coupland’s research group [8-14] in the department of molecular and clinical cancer medicine. The research will focus on the detailed physical structure and chemical composition of spherical cultures of cancer cells grown in chick embryos by Prof Sarah Coupland’s group. It will use a range of state-of-the-art experimental techniques developed in physics by Prof Weightman’s group including a world leading scanning near field optical microscope developed on the infrared free electron laser on the ALICE accelerator at Daresbury, with support from the EPSRC, and which has recently been moved to Liverpool in support of a research programme funded by Cancer Research UK [6] for the early detection of oral cancer.

Prof’s Coupland and Weightman will be joint supervisors of the PhD and the student will be a member of both their research groups.
Scientific Objective: The primary objective will be to understand how the 3D structure of the spheroids influences the diffusion of oxygen into structure and how this influences the metabolism of tumours.

Name and email address to direct enquiries to: Prof Peter Weightman,

Funding Notes

The post is open to EU/UK candidates and provides full tuition fees and a stipend at UKRI standard rates (currently £14,777 p.a.).
Some teaching duties may be required to be carried out during the PhD studentship.

References

1 "Near-field optical microscopy with an infra-red free electron laser applied to cancer diagnosis", Smith AD et al App. Phys. Lett. 102 053701 (2013)
2 "Imaging cervical cytology with scanning near-field optical microscopy (SNOM) coupled with an IR-FEL." Halliwell et. al. Scientific Reports, 6 29494 (2016)
3 “An evaluation of the application of the aperture infrared SNOM technique to biomedical imaging.” Ingham et. al. Biomed. Phys. Eng. Express 4 025011 (2018)
4 "Submicron infrared imaging of an oesophageal cancer cell with chemical specificity using an IR-FEL" Ingham, et. al. Biomed. Phys. Eng. Express 5 015009 (2018)
5 "SNOM Imaging of a Crypt-Like Feature in Adenocarcinoma Associated with Barrett’s Oesophagus" Craig T. et. al. Phys. Stat. Sol. B 1700518 (2018)
6 “Early detection of oral cancer using infrared imaging.” Cancer Research UK C7738/A26196
7 "Application of a quantum cascade laser aperture scanning near-field optical microscope to the study of a cancer cell" Smith CI et. al. Analyst 143 5912 (2018)
8 Fiorentzis M, et al. Conjunctival melanoma and electrochemotherapy: preliminary results using 2D and 3D cell culture models in vitro. Acta Ophthalmol. 2018 Dec 10. doi: 10.1111/aos.13993.
9 Leedale, J. et al. Modeling the dynamics of hypoxia inducible factor-1alpha (HIF-1alpha) within single cells and 3D cell culture systems. Math Biosci (2014) 258C, 33-43.
10 Sandt C et al. Use of infrared microspectroscopy to elucidate a specific chemical signature associated with hypoxia levels found in glioblastoma. Analyst (2016) 141, 870-883.
11 Al-Mutawa YK et al., Effects of hypoxic preconditioning on neuroblastoma tumour oxygenation and metabolic signature in a chick embryo model. Biosci Rep. 2018 Aug 29;38(4).
12 Kalirai H et al. Use of the chick embryo model in uveal melanoma. Ocular Oncology and Pathology, 2015 Apr;1(3):133-40
13 Herrmann A. et al., The chorioallantoic membrane of the chick embryo to assess tumor formation and metastasis. Methods Mol Biol. 2016;1464:97-105.
14 Swadi R et al., Optimising the chick chorioallantoic membrane xenograft model of neuroblastoma for drug delivery. BMC Cancer. 2018 Jan 4;18(1):28.

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