Qualification Type: | PhD |
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Location: | Norwich |
Funding for: | UK Students |
Funding amount: | £19,237 for a maximum 3 years |
Hours: | Full Time |
Placed On: | 26th November 2024 |
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Closes: | 1st January 2025 |
Reference: | SobolewskiA_U25SCI |
Primary supervisor - Dr Anastasia Sobolewski
Non-small cell lung cancer (NSCLC) is diagnosed at a late stage and has a poor prognosis. Although some targeted treatments exist, chemoresistance frequently occurs. One mechanism through which chemoresistance can happen is through tunnelling nanotubes (TNTs).
TNTs are long cytoplasmic extensions that exist between cancer cells in the tumour microenvironment, and can be up to several hundred microns in length. TNTs are responsible for the trafficking of organelles ¬¬such as mitochondria, which can confer a more metastatic and aggressive cancer phenotype.
Understanding how TNTs are regulated are important for understanding new targets for therapeutic intervention.
Our research has shown that certain growth factors and cell surface receptors called integrins dysregulated in NSCLC, modulate TNTs (Awanis et al.2023). Integrins bind the extracellular matrix like collagens, and strikingly in the tumour microenvironment, cancer cells sit on a much stiffer matrix than healthy cells. This stiffness can cause the mechanical activation of different cell signalling pathways (Johnson et al. 2024), which we think can contribute to TNT formation.
This study will determine how:
i) Growth factor integrin and extracellular matrix signalling crosstalk controls TNT formation
ii) Stiffness of the tumour microenvironment regulates TNTs through mechanosensing cell signalling pathways
iii) Interplay between integrins and matrix stiffness regulates TNTs
The student will gain experience in tissue culture, time lapse, confocal and fluorescence microscopy, scanning electron microscopy, siRNA knockdown, Western blotting, mechanotransduction assays, hydrogels, prizm and Image J software analysis. The student will work independently towards objectives set through discussion with the supervisors. In addition to regular lab meetings the student will present their research within the School and at the Norwich Cancer Research Network conference, which will also provide an opportunity for networking, as well as at public engagement events like the Norwich Science Festival.
Entry requirements
The standard minimum entry requirement is 2:1 (Hons) in Pharmacology, any biologically related science degree such as Biological Sciences, Biochemistry, Biomedicine, Pharmacy.
Start date: 1 October 2025
Funding Details
Additional Funding Information
This PhD project is a Faculty of Science funded studentship. Funding is available to UK applicants and comprises ‘home’ tuition fees and an annual stipend of £19,237 (for a maximum 3 years).
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