by: Sophie Fiola
I study a type of brain tumour called low grade glioma. These are tumours that arise in young, otherwise healthy people. Right now, the best possible treatments we have for low-grade gliomas are surgery, radiation and chemotherapy. The problem with these treatments is that they’re not very specific and have a lot of side effects. Chemotherapy, for example, affects all the cells in your body. It just so happens that it affects cancer cells more because those grow faster. That’s the reason chemotherapy has so many toxic side effects.
For my thesis, I want to find better treatments for low grade gliomas using an idea called synthetic lethality.
Let’s say you have Gene A and Gene B. If you have a mutation in only Gene A and in only Gene B, your cells will survive. But a mutation in both Gene A AND Gene B results in cell death. The cool thing about synthetic lethality is we can design really specific treatments against really specific cancers. This way, if I target B, only the cells that already have a mutation in A will die.
Now, back to our original question. What do beer, bread and brain tumours have in common. Well, that would be… yeast! I want to look for Gene B using yeast.
Now, some of you might be thinking: “Yeast don’t have brains, so how could they possibly be used to study brain tumours?”. Well, it all comes down to this little molecule called 2-hydroxyglutarate, or 2HG for short. 90% of all low grade gliomas have this really specific mutation in which cells make too much of this molecule, 2HG. We haven’t really figured out how, but it’s this molecule that leads to the formation of cancer.
So, I gave my strain of yeast a mutation so that they made too much of this molecule, 2HG. This is my Gene A. And then, I did a screen to try to find Gene B. To do this, I mated our strain with 5000 different strains of yeast, each of which had a mutation in a different gene. And then I looked for cells that died. And guess what? I found a Gene B! We found that a mutation in a specific gene causes cell death, but only in cells that already make too much 2HG.
This is interesting because in the future, we could maybe make drugs that also target this gene. And this isn’t just a target for low grade gliomas. There are other types of cancers that make too much 2HG, like certain types of blood and breast cancers. This has the potential to treat a lot of people.
Now who would have thought I could figure all this stuff out with a single-celled, brainless organism? The next time you eat a slice of bread or drink a beer, remember: yeast, also for brain tumours.
