Abbie Fearon, ETH Switzerland
Kat - Iíve been off on my travels over the past month, including taking a trip to a Gordon Research Seminar at the Chinese University of Hong Kong, which was focusing on molecules known as fibroblast growth factors, or FGFs. But what are they? And what do they do? Abbie Fearon, a researcher from the Swiss Federal Institute of Technology in Zurich and co-chair of the meeting, gave me the low-down.
Abbie - Our cells need to be able to grow and divide, be able to form organs and basically make up the whole human body. To be able to grow, they need to be able to communicate with each other. And so, the growth factors are really important because thatís how the cells communicate to each other. So, one cell will release growth factors and they will then go across to another cell and theyíll bind to another protein that sits on the cell and then that transfers a message into the cell that tells the cell to grow and divide.
Kat - The conference that weíre at is looking at fibroblast growth factors. What are they? I mean, what's a fibroblast for a start?
Abbie - So, fibroblasts are a specific cell type and the name fibroblast growth factor is actually slightly confusing. Itís basically these proteins were originally found in fibroblasts. Itís thought that the people who discovered them basically found these proteins, chucked them on a specific cell type, found that it made those cells grow and divide and so, just called them fibroblast growth factors. But they're actually really important in loads of different types of cells.
Kat - How many different sorts of these growth factors Ė these FGFs - are there?
Abbie - So, there are 23 different FGFs I think. There are probably 23 different FGFs and there are 4 different FGF receptors. And so, each of these different FGFs binds to another protein called an FGF receptor. And that's how the signal gets transmitted into the cell. Each of these different fibroblast growth factors binds to different receptors and so thatís how you get sort of different signalling through the different pathways.
Kat - Because these were involved in making lots and lots of different parts of the body. So at some point, there has to be a Ė you're the signal to make that part of the brain and you're the signal to make that part of the body.
Abbie - Exactly and thatís what's really important. So, FGF receptor 2 for example is what I worked on for my PhD and thatís particularly expressed in the uterus. And so, only certain FGFs will bind to receptor 2 and will tell the uterine cells to grow and divide. But there can be other FGFs around and in the uterine cells that won't bind to that specific receptor and so therefore, you get this specificity that tells different cells to grow at different times and thatís also important that the FGFs are released at different times which makes the cells grow at different stages.
Kat - Itís all about getting the right cells doing the right thing at the right time in the right place to make an organism.
Abbie - Exactly, yeah. And thatís one thing that goes wrong in cancer. So these FGFs are really important. Theyíll go wrong in cancer quite often so though they're really tightly regulated. So the signal only happens a specific time. But in cancer, we can have loads of these receptors for example that just signal without having any of the FGF bound to it. So then you'll lose all the specificity. And so then the cells just grow and divide uncontrollably.
Kat - Itís just saying, ďGo! Go! Go! And do this.Ē
Abbie - Exactly, yeah.
Kat - And so, what are some of the things that we now know about these FGFs and how can we use that knowledge?
Abbie - And so, FGF receptors are particularly important for example in cancer. So there are drugs that will bind to the FGF receptors and can block them. And so, if we know that we can block the receptors then we know that we can Ė if this certain cancer is particularly reliant on that mutated FGF receptor, so the one thatís over active, if we can block that using a drug then we can maybe treat patients who have got mutations in this specific receptor.
Kat - But how does the cell know which signals to listen and what's actually coming in if there's all these kind of signals and noise going on?
Abbie - There will always be a level of background noise. So you'll always have these multiple different proteins that are doing similar sort of things. But then you'll have a predominant pathway. So, thatís particularly important when you have these different cells that are interacting. So you get some proteins, some FGFs that are released from a certain cell and you will have more of that protein in the mixture. So, that signal will be the predominant signal.
Kat - Itís kind of like whoever is shouting loudest at that time gets heard.
Abbie - Exactly, yeah. Thatís an excellent way of putting it.
Kat - Weíre studying all these different kinds of signals and how cells communicate and how cells know what to do. Tell me a bit more about the work that you're doing? What are you studying particularly?
Abbie - So right now, for my post-doctoral research, I work on the liver and the liver has this amazing capacity to be able to regenerate so we can chop off about two thirds of the liver and it will grow back almost perfectly fine. Itís the only organ that can do this so itís really interesting to understand how that happens. And whilst we have a broad overview of that knowledge, we really need to understand a little bit more how it does this. So, my work at the moment is predominantly focused on trying to figure out how the liver regenerates.
Kat - So, you're studying the sort of signals that say, ďAhh! Something awful has happened. Quick! We need to grow.Ē
Abbie - Exactly. So, these signals that are probably really important in development and then get switched off in normal healthy humans are then somehow reactivated once the liver has had this massive injury. For example, just chopping some of it off and those signals can be reinitiated. Itís amazing that the liver can do this, but this isn't seen in other organs. So, there's lot of scope to why this might be relevant to lots of different tissues.
Kat - That could really be amazing, could it, if you could just add the right growth factors and ďAhh! I can grow my kidney back again because my kidney has become diseased or grow my arm back again, so chop my arm off.Ē Is that a future that we could be looking at?
Abbie - I mean, I think thatís very, very far in the future and far away, but I suppose Ė I mean, this is the great thing about basic sciences. You donít know where itís going to end up. There are lots of different research projects that had started off just being, because we donít understand what's happening and then it ended up being there are treatments for cancers. So in the future, that could be really interesting.
Kat - Itís something that people donít really think about that all our cells have got this crackling network of communication and all these signals being sent around. Is that how you view biology Ė this sort of network of signals?
Abbie - Yeah, completely. Itís really strange now when I sometimes think about. In the day, I'm so focused on this one small thing but then you'd like to see them out slightly and itís this whole network of everybody talking to each other and there's so much background noise, and how do we get the specificity. Yeah, itís very, very visual in my mind then weíre all talking.
Kat - It must be like sort of sitting and being bombarded by a hundred different TV channels at once.
Abbie - Exactly. Itís just one massive conversation and then trying to break that down. Itís difficult but just absolutely fascinating to me.
Kat - Abbie Fearon from the Swiss Federal Institute of Technology in Zurich.