Prof K Al-jamal, Prof Claire Wells
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
Pancreatic cancer (PC) currently has no effective treatment. The development of exosomes as delivery systems for biologics is an emerging topic in the field of cancer therapy. An attractive target is the PAK family kinases (PAK1-6) many of which are overexpressed in pancreatic cancer and have previously been shown to drive both proliferation and cell invasion.
This 3+1-year project aims to validate the role of PAK family in PC progression using a combination of gene-editing approach and exosomal delivery (nanomedicines).
In the rotation project, the candidate will learn techniques such as culturing PC cells, isolation and characterisation of exosomes: size and surface markers (CD81/CD9) by nanoparticle tracking analysis and flow cytometry, respectively. Exosomes will be fluorescently labelled and uptake in cancer cells will be studied by flow cytometry.
Plans for Years 1-3 are as follows:
Year 1: Target validation and engineering of exosomes
Initially, the role of PAK family genes will be studied by siRNA technology using commercial transfecting reagents. The two most effective genes will be picked up for subsequent CRISPR-gene-editing studies. Exosomes (as carriers) will be engineered to carry Cas9/gRNA complex (therapeutic cargo).
Year 2: In vitro efficacy studies
The ability of exosomes to deliver Cas9/gRNA complexes into pancreatic cancer cells will be studied by flow cytometry. Gene-editing and effect on cell proliferation will be studied by molecular biology techniques (PCR, Western Blotting, T7 assay) and cell proliferation assay, respectively.
Year 3: In vivo biodistribution and therapy studies
Quantitative uptake of exosomes will be assessed in orthotopic pancreatic cancer mouse model by ex vivo gamma counting. Therapeutic effect will be monitored by measuring tumour size by live animal bioluminescence imaging.
This project is under Theme 1, Molecules, Cells, and the Basis for Disease.
Funding Notes
Please note that MRC DTP Projects offer both a ‘0+3.5’ PhD only track, and a ‘1+3’ MRes/PhD track with laboratory rotations.
To apply to the MRC DTP in Biomedical Sciences (https://kcl-mrcdtp.com/), please visit the webpage (https://kcl-mrcdtp.com/application-process/) to submit an online application via King's Apply (https://apply.kcl.ac.uk/)
Further information and FAQs are available at: https://kcl-mrcdtp.com/faqs/
References
Bai J, Wang J T-W, Rubio N, Protti A, Heidari H, Elgogary RI, Southern P, Al-Jamal WT, Sosabowski JK, Shah AM, Bals S, Pankhurst QA and Al-Jamal KT. (2016) Triple-modal imaging of magnetically-targeted nanocapsules in solid tumors in vivo, Theranostics. 6(3): 342–356.
Helen King, Kiruthikah Thillai, Andrew Whale, Prabhu Arumugam, Hesham Eldaly, Hemant M Kocher and Claire M Wells (2017). PAK4 interacts with p85 alpha:implications for pancreatic cancer cell migration. Nature Scientific Reports 7:42575
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