Ubiquitous proteins, empty noses

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Health Report 28 min 2 speakers 8 chapters transcribed 1 day ago

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What is Empty Nose Syndrome and why is it so hard to diagnose?

Joel Werner 0:00

Hey, I'm Joel Werner. This is the Health Report, and today, a poorly understood, frequently misdiagnosed condition that leaves the people it affects in a world of physical and psychological discomfort.

Erica Schneider 0:13

Your brain is hijacked by this feeling of suffocating every minute of the day and psychologically you just are in this panic state and then you have this physical anxiety from, you know, the breathing. So it all is extremely crazy.

Joel Werner 0:33

That's Erica Schneider, and she's felt like that for 13 years. We'll find out why later in the show. But up first, Darren Saunders is the kind of scientist who goes on mountain biking holidays with his mates, and he's also a cancer researcher who recently set up a unique collaboration. To set the scene, the story centers on a truly ubiquitous protein.

Darren Saunders 0:58

So we've been interested for a really long time in this system called the ubiquitin system. Now it's called ubiquitin, it's the name of a gene because it's everywhere. In every cell we look at, we find this gene switched on. And what this gene does is make a little protein that's kind of like a flag that gets stuck on other proteins in your cell. And that little flag tells your cell what to do with the protein. So it could flag it to get destroyed, like taking out the garbage if you like, or it could flag it for recycling to get taken to an Another part of the cell broken down and then remade into new proteins. Or it can help the cell signaling, it can help cells switch on the way that they communicate with each other and communicate with inside the cell.

Darren Saunders 1:33

And people, not just me, lots of people have been interested in this system for a very long time. It was discovered 30, 40 years ago, and the guys that discovered it won the Nobel Prize. And it's important in the way your immune system works, it's important in the way your brain works, basically everything. Mm.

Joel Werner 1:50

With your

Darren Saunders 1:50

work in cancer, what role were you thinking the ubiquitin

Joel Werner 1:55

system might play there?

Darren Saunders 1:56

Right. So it turns out that to be a cancer cell is a really stressful situation. So you have extra copies of DNA floating around, you've got mistakes in the genome, the metabolism of the cell has kind of gone out of control. And in order to deal with that, the cell needs to be able to handle this stress. Now we call that proteostasis. It's a big word, but it basically means maintaining normal protein chemistry, if you like. And one of the way the cells do that is using this ubiquitin system. And so for a long time people have been looking at this system as a therapeutic target. And there are therapies out there in the clinic that target this. So there's a drug called Velcade, which is used for multiple myeloma.

Darren Saunders 2:32

And basically the way that works is that if you take a cancer cell that's very stressed out and you take away its capacity to respond to that stress, the cancer cell dies. And now we're looking at that in a whole bunch of different contexts in cancer. What other context here? So so we think most cancer cells do this. The way we're approaching it is we're able to use a method that lets us look at all of the proteins in the cell that are flagged with this little ubiquitin tag. So we can do it sort of systematically. We smash the cells up or we smash up some tissue and we run it through a machine called a mass spectrometer, which is able to measure things very accurately. And that gives us a sort of a map, if you like, of what's being ubiquitulated or flagged with this little ubiquitin protein.

How does the ubiquitin system work and why is it important for cancer research?

Darren Saunders 3:09

at any one time. And what we're interested in is whether or not we can find specific proteins in the cell that we have drugs against that we can switch off and try and kill the cell. That's the the kind of principle behind it.

Joel Werner 3:20

Now what's super interesting about the work you're doing, apart from the work itself, is its potential application to another area of medical research. Before you describe what that application is, can you tell us about how this collaboration came about? It's seemingly rare in modern science for people to peer over the backyard fence of another researcher and say, Hey, we could actually work together.