Jennifer Symonds - Building glands
Kat - To find out a bit more about how FGF signalling is involved in building different parts of the body as a baby grows in the womb, I spoke to Jennifer Symonds, from the National Institute of Dental and Craniofacial Research in Bethesda, Maryland, who's focusing on the role of these growth factors in making your mouth water - building the salivary glands that produce saliva - or spit, as it's more commonly known.
Jennifer - So, we want to understand what are the different stem cells within the human salivary gland. So, most people don't think about salivary glands every day because they work. But when they stop working, you really miss them. And so, with salivary glands, they provide saliva which lubricates the mouth that helps for you to eat. But it also just maintains your oral health. So a lot of people who have salivary gland issues, they have a lot of dental caries or cavities, and they have a lot of dental health issues, and their lives are very uncomfortable and can be very painful. And so, in our laboratory, we're trying to understand what's going on with the normal salivary glands so that we can develop therapies for patients who are not making enough saliva. And to do that, we are looking at the different stem cells so that maybe we could turn these stem cells back on after damage like radiation or due to other diseases that can cause defects in salivary flow.
Kat - So let's kind of go a little bit right back to basics. Where do our salivary glands come from? How do they start being made?
Jennifer - So you have 3 major salivary glands and the next time that you bite into something sour like an orange or if you take a sip of soda, you'll feel little pings in the side of your cheeks and those are your salivary glands turning on because it's time to eat. You'll never notice it until you think about it. Now, every time that I eat, I can feel them, these little tingly feelings in the sides of my cheeks. Those are the salivary glands turning on. And so, they develop really early in development. So, your tongue actually is two pieces and when your tongue fuses together, that is when your salivary glands start. So, right when your face is starting to look like a face, that's when the salivary glands start.
Kat - So, this is when like a human or an animal is growing in the womb and it's all kind of coming together.
Jennifer - Yes.
Kat - It's that early stage.
Jennifer - Very early stage, absolutely.
Kat - How do you go about studying and trying to figure out what's going on there?
Jennifer - So, we use mouse models in our laboratory but you can use other animal models too. And so, we also use pigs. We have micro pigs that we are looking at in collaboration. I, unfortunately don't get to work with the pigs. They look very cute. But yes, we study it in developing mouse embryos.
Kat - What are you starting to understand about how the salivary glands form and maybe what's going wrong in some cases?
Jennifer - So, the different cells within the salivary gland, they have to divide so that they can make up the salivary gland as it develops because it starts off as this very, tiny, tiny little thing and it has to grow to be quite large because the salivary glands in the human, they take up a good portion of your cheek.
Kat - What do they actually look like and what's the sort of the structure of salivary gland? I can poke my face and I can't really feel anything. What does it look like inside?
Jennifer - It actually looks like a tree. And so, a salivary gland is a branching organ. And so, like the branches of a tree, if you imagine the branches of a tree are kind of like the highways of saliva that go into your mouth and then the leaves of the tree are where the saliva is formed. And so, it kind of looks like a bush or a tree, but it looks quite fluffy. It's actually a very pretty organ because it has all of these small circles at the end that make the saliva.
Kat - It's a fluffy tree full of spit.
Jennifer - It's a fluffy tree full of spit, absolutely. And you have three of them on each side of the face.
Kat - What do we now know about the kind of the genes that are controlling how these are made? What have we started to discover?
Jennifer - So we started to see that some of the genes that are important for other organs all over your body are also important in salivary glands which is very exciting for not just people who study salivary glands like me, but for people who study other organs that resembles salivary glands and some that don't. And so, there are certain markers of cells that we know marks the different progenitor stem cells within these different tissues. And a lot of them they're the same in mammary gland and in pancreas and in other tissues.
Kat - So you might not think that your mammary glands, your breasts have anything to do with your salivary glands, but they're kind of similar then.
Jennifer - They're very similar. And so, if you imagine the tree again, mammary glands are exactly like a tree that make milk. And so, the leaves make milk and it goes through the branches of the tree and then out the main duct. And so, many different organs in your body have that tree kind of shape which is why we call them branching organs.
Kat - As the salivary glands, mammary glands are developing, there have to be signals that say, "Okay, we're going to do this here. We're going to make this organ and do this branching." What are those signals? What have you discovered about how they're working?
Jennifer - So, there are specific proteins that are secreted by certain cells in these branching organs. One that I'm studying is called fibroblast growth factor and we call it FGF for short. What we found in the salivary gland and it's the same in other branching type tissues like mammary gland is that you need FGFs in order to steer these signals to make these branches because like when a tree grows, you start with one shoot, maybe a few leaves and then you get multiple different boughs and branches, and multiple leaves. We know that these factors - FGFs - are essential for this whole process.
Kat - Is it the same FGFs that are in the salivary glands or in the pancreas or in other tissues because there's lots and lots of different types of FGFs, isn't there?
Jennifer - That's right. There's many types of FGFs and what we have found is that certain FGFs are especially important for this branching. And so, my work has shown that FGF 10 and the signalling that happens downstream or what I mean is, after the growth factor, this FGF comes in contact with the cells, there's lots of activity inside the cell. And so, this particular FGF, FGF 10 is important for all of these branching organs.
Kat - I guess that's kind of quite clever evolutionary trick then. As if you need to make something that branched that releases fluid like pancreas or breasts or salivary glands, you kind of do it in the same way.
Jennifer - Yes. These mechanisms are absolutely conserved which is a brilliant trick of nature if you like to think of it that way. And so this way, you don't have to use all these different genes. It's nice in development because you only have certain pathways that you can use, but it's also nice for therapy. Because that means that what I find in the salivary gland could be used to help people who have problems with their pancreas or maybe with your tears. Your tears are also made from a branching organ. Your lungs are also a branching organ. And so, the things that I have found in the salivary gland could also be used to treat people with defects in their lungs, in their kidneys, pancreas, any branching organ.
Kat - So I guess by using these same kind of pathways, the same molecules, it means that really, there isn't such a thing as salivary gland gene that makes a salivary gland or a breast gene that makes your boobs.
Jennifer - That's absolutely right and sometimes I know that I wish there was a salivary gland gene. It would make my life a lot easier. But on the other hand, it's very fascinating to me that the same pathways are used in different organs that do different things at different stages of development, and even in different disease states. And so, it's also important to note that the pathways I study in salivary glands, these FGFs, they're really important for cancer because these same pathways that are essential for normal development get altered in cancer. And so, it's nice that the things that I learn about normal FGFs, I can apply to cancer. And so, it's kind of like piecing a part of the puzzle and you already know the pieces but they're going to fit together differently.
Kat - It's kind of the solution, isn't it to how we only have 20,000 genes but we may call these amazing different tissues. I sometimes think it makes biology really simple because you're only dealing with this many genes. But actually, it's really complicated because all these genes do lots and lots of different things.
Jennifer - I don't know if you played with Legos or building blocks as a child but I did. I love Legos. I still play with Legos. Biology is a lot like Legos. All the different pieces, they sound so simple. You have 22,000 genes that, it's not that many really especially you and I are both sitting here, we're both women. We're very different people. It's because of our 22,000 genes. It's the way the different Lego pieces are fitting together. And so, once you know some of the rules, you can see how you can take the same Lego pieces and you can build an airplane, you can build a castle, you can build a Star Wars thing like I did over Christmas. You can do lots of things with Legos and genes are the same way. And that's why you can use these same genes to develop a salivary gland, develop mammary gland, lots of different things because they're just like Legos.
Kat - What's going to be the journey from the kind of lab studies that you're doing to finding these treatments? Is this just the first steps along the pathway?
Jennifer - These are some of the first steps. In our laboratory, we have multiple projects to look at this. In one of them, we're treating with another secreted growth factor called Nuturin and it influences the nerves within the salivary gland. And so, one of our - it's a little closer to the clinic than where I'm currently working on is, we hope that if we can give Nuturin to patients in their salivary glands that have lost salivary gland function, that maybe we can turn back on the salivary gland. And so, that's a little bit closer to therapy than yes, the very early stages of my personal project on FGFs.
Kat - Now, you're having a quick sip of coffee, can you feel your salivary glands working?
Jennifer - Yes, we can. Coffee is rather bitter so they do turn on but seriously, everyone should take a sip of lemonade. It's beginning to be very hot. It's hot where we are here in Hong Kong. If you take a sip of cold lemonade, you'll be able to feel your salivary glands turn on. It's really fascinating that you can feel this. And so, the next time that you're eating, try to remember that your salivary glands are working really hard for you to have a healthy life. We should really care about salivary glands even though most of the time they work just fine and we don't even realise they're there.
Kat - Jennifer Symonds, from the US National Institute of Dental and Craniofacial Research.