Recipient organisationCardiff UniversitySource-published name: Cardiff University
Funding£1.3M
PeriodMay 2023 — May 2027
In plain English
AI plain-English summary
Glioblastoma cells that are more aggressive contain more protein than their less aggressive counterparts, and this project will investigate why. This matters because glioblastoma is the most aggressive adult brain cancer, with no cure and a typical survival of just 15–18 months after diagnosis. The tumours are a diverse mix of cell types, and the most aggressive cells drive regrowth after treatment. Understanding how these cells produce and manage excess protein could reveal a vulnerability that current treatments miss. The research focuses on a protein called HECTD1, which controls the ribosome—the cell’s protein-making factory. If HECTD1 helps aggressive cells churn out more protein, blocking it might stop tumours from regrowing. The team will also test a new microscope technique that measures protein levels in individual cells, using human patient samples to see if it can identify aggressive cells faster and more sensitively than existing methods. This is fundamental science: it explores a basic mechanism of cancer cell behaviour. If successful, it could lead to new drug targets or a diagnostic tool that helps clinicians spot the most dangerous cells, improving treatment planning for a disease that currently offers patients few options.
View original technical description
Glioblastoma is the most aggressive type of brain cancer in adults. There is no cure, and most patients die within 15-18 months after diagnosis, even with treatment. Developing effective therapies against glioblastoma is very difficult, because these cancers are made up of a very diverse mixture of different cancer cells. We have found that a type of glioblastoma cells that is more aggressive than other cells from this cancer also contains more proteins than less aggressive glioblastoma cells. We think this allows more aggressive glioblastoma cells to grow quicker which helps these cells to be more aggressive and regrow into new tumours after treatment. Our project will investigate differences in proteins between more aggressive and less aggressive glioblastoma cells to find new ways for treating glioblastoma by stopping more aggressive cells from growing. We want to understand how protein production is conducted in each glioblastoma cell type, and we will combine different ways of investigating proteins inside glioblastoma cells. This will allow us to study not only the type of proteins being made, but also how they interact with one another and how they are broken down. As part of our project, we will investigate the protein HECTD1 since it controls the factory which makes proteins, called the ribosome. We will test whether HECTD1 helps more aggressive glioblastoma cells to make more protein and therefore helps glioblastomas to grow back after therapy. This may help find new ways of treating glioblastoma. Finally, we are using a new type of microscope for measuring protein amounts inside glioblastoma cell types and this is exciting because this technology has the potential to readily identify more aggressive glioblastoma cells, with increased sensitivity and quicker than ever before. We will test this in human patient material to evaluate its diagnostic/prognostic value. This new technology could help other scientists and clinicians in the future by making it easier to identify and study more aggressive cancer cells.
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