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(ACED Non-Clinical) Development of a 3D in vitro lung cancer model to track genetic instability


Project Description

This interdisciplinary project will utilise a variety of material science and biological approaches to create an improved in vitro lung tumourigenesis model that can be used for therapeutic pre-clinical testing and biological mechanistic study. The projects overall goal will be to build an in vitro 3D tissue engineered model that closely mimics human lung tissue. This model can then act as test bed for understanding how different factors can initiate cancer in the lung.

The 3D tissue will be engineered using electrospun fibrous polymer scaffolds, that will provide an underlying physical support to primary murine endothelial cells. A bioreactor will be designed to house the 3D tissue and provide suitable air/fluid physiological boundaries. The model will then be tested and optimised for 3D tissue growth to determine if the engineered tissue offers a reliable mimic of lung physiology.

A variety of factors will then be applied and altered to the system such as (i) the application of mechanical forces to the developing construct to mimic the strains experienced locally during inhalation / exhalation, (ii) varying levels of oxygen and (iii) application of cigarette smoke. The levels of genomic damage and gene expression changes as a result of these factoral changes will be assessed.

Once the model has been established as described above with wildtype cells, KRAS mutant and KRAS/p53 double mutant cells will be cultured in the in vitro model to establish an in vitro tumourigenesis lung model and the responses to the mechanical forces, oxygen and cigarette smoke exposure will be assessed and compared to wildtype response.

The PhD student will co-create this project in conjunction with the lead supervisor (Prof Sarah Cartmell), a biologist working on lung tumourigenesis (Prof Angeliki Malliri) and a cancer biologist (Andrew Gilmore).

Entry Requirements

MCRC Non-Clinical
For Non-Clinical Studentships, candidates must hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in a relevant subject. A related master’s degree would be an advantage. Applications from all nationalities are welcome.

Please formally apply via the University of Manchester application portal; this will include adding your CV, obtaining referees and submitting a personal statement (1000 words max) Please comment on your suitability for the post, giving an overview of your relevant experience and training.

https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mcrc-training-scheme/

Funding Notes

MCRC Non-Clinical

This Project is funded through the CRUK as part of the International Alliance for Cancer Early Detection (ACED). This four year Studentship will cover an annual stipend (currently at £19,000 per annum), running expenses and PhD tuition fees at UK/EU rates. Where international student fees are payable, please provide evidence within your application of how the shortfall will be covered (approximately £19,000 per annum).


As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Shelley D Rawson, Jekaterina Maksimcuka, Philip J Withers, Sarah H Cartmell X-ray Microscopy; Bringing New Insights to the Life Sciences. accepted by BMC Biology (in press)

Alyah H. Shamsah, Sarah H. Cartmell, Stephen M. Richardson, Lucy A. Bosworth “Mimicking The Annulus Fibrosus Using Electrospun Polyester Blended Scaffolds” 2019 Nanomaterials 2019 Apr 3;9(4)

Ruikang Xue, Benedict Chung, Maryam Tamaddon, James Carr, Chaozong Liu, Sarah Cartmell “Osteochondral Tissue Co-Culture: An In Vitro and In Silico Approach” 2019 Biotechnology & Bioengineering 2019 Nov;116(11):3112-3123

Lucy Ann Bosworth, Wanxiao Hu, Yingnan Shi and Sarah Cartmell, “Enhancing biocompatibility without compromising material properties: an optimised NaOH treatment for electrospun polycaprolactone fibres” Journal of Nanomaterials Volume 2019, Article ID 4605092, 11 pages
https://doi.org/10.1155/2019/4605092

Huh, D., Matthews, B.D., Mammoto, A. Montoya-Zavala, M., Hsin, H.Y., and Ingber, D.E. Reconstituting Organ-Level Lung Functions on a Chip. Science 2010: 1662-1668.

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