Investigating extracellular vesicle mediated cell-to-cell communication as a disease mechanism
Lab rotation project description
The rotation will introduce the student to a range of techniques which will be essential for the project:
- Week 1: Lab inductions/Introduction to cell culture
- Week 2-3: Cell culture and microscopy
- Week 4-5: Vesicle isolation
- Week 5-6: Western blotting and other molecular techniques
- Week 7: DTP report writingTraining: Cell culture, vesicle isolation, western blotting.
Molecules, cells and organisms
School of Veterinary Medicine and Science
Linked PhD Project Outline
Once thought to be little more than a way for cells to offload waste, extracellular vesicles (EVs) are now recognised to be a deliberate way for a cell to secrete cargos of RNA, DNA and proteins to reshape tissues and act as signal carriers. These somewhat overlooked organelles may hold the key to understanding how tissues and systems in our bodies communicate, particularly within complex diseases (e.g. cancer and dysfunctional immune cells). Our work is the first to look at how the cargo of cancer EVs selectively reprogramme the cells of the bone to create a supportive pre-metastatic niche; to promote cancer spread. When prostate cancer metastasizes, it predominantly spreads to bone. The reasons for this remain unclear and cannot be simply explained by the circulating pattern of blood flow.
This project will explore how the type of EV released by cancer cells changes depending upon their co-culture environment, exploring the hypothesis that a specific mechanism of communication exists between bone cells and prostate tumour cells and providing proof of principle that such mechanisms exist to remodel tissues in pathological states.
The above aims will be achieved though the following:
- Prostate cancer cell lines with different bone-metastatic propensities within in vivo models will be used to compare changes in vesicle characteristics and protein cargos.
- The effect of cell-to-cell communication on prostate cancer EVs will be determined by exposing prostate cancer to the same environment as stromal bone cells (cells present at sites of prostate cancer metastasis).
- Manipulation of prostate cancer EVs to determine their influence on bone stromal (metastatic site cells) behaviour.