Aquaporin 4: water and our brains

Interviewer: Sam Walter (Interviewer, Ideas Lab)
Guest: Dr Alex Conner
Recorded: 04/04/2014
Broadcast: 02/06/2014

Intro VO: Welcome to the Ideas Lab Predictor Podcast from the University of Birmingham. In each edition we hear from an expert in a different field, who gives us insider information on key trends, upcoming events, and what they think the near future holds.

Sam: So today we’re with Dr Alex Conner, who is a Senior Lecturer in Medical Sciences, here at the University of Birmingham. Hello Alex. 

Alex: Hello.  

Sam: So can you tell us a little bit about what you do here at the university?

Alex: Yeah, sure. So I’m slightly unusual in that I have something of a portfolio career here. I’m a Senior Lecturer in Medical Sciences, which means I teach general medical sciences to lots of students. I’m also a professional trainer and facilitator of non-academic courses and also facilitating conferences and I run a small research group looking at protein structure and function.

Sam: Fantastic. So how do those things all intertwine? How does having this other aspect to academia influence your research?

Alex: With business, but they have an added value. Each influences the other. I think I’m a teaching-led researcher, so they definitely help each other. When I’m teaching courses in academia that can influence how I teach. Training courses and the skills using that directly influence how you do other teaching and the other research is influenced by the teaching of course as well; they’re on the same sort of area.

Sam: Tell us a little bit about the research that you do here. What’s that in?

Alex: So I study protein structure and function. Proteins are tiny, tiny molecules inside human cells, in all cells, and they pretty much run everything we do. I’m interested in the ones that are outside of the cell, going through the membrane that transmit signals from outside to inside the cell and vice versa. A little bit like your hand turning on a light switch and then something happens. I’m interested in what it is that happens, what it looks like and how we can use that for therapies in the future.

Sam: What specific therapies? Are there any specific things that the cells you’re researching will help?

Alex: Yeah, one example is the protein aquaporin 4. This is found in the brain, specifically in astrocites, which means star cells, and this allows water to come in and out of the brain. Normally we have to regulate the size of the cells and one way we do that is through the swelling of them through water and  aquaporins are literally a water hole that lets water come in and out. And sometimes that goes wrong. For example, when you get a bang on the head, sadly like Michael Schumacher currently is experiencing, or if you have a stroke you can get brain swelling and this is thought to be through aquaporin 4. As water comes into the brain, from the bloodstream, swells up the brain and causes brain damage and even death.

Sam: How do these proteins react when we say we have a brain injury?

Alex: That’s a very good question. So these, think of them like doors of the cells and water can come through the door. What we’re interested in is what shape this door is, whether we can remove the doors so these aquaporins go inside the cells sometimes and we regulate that or we try and understand ways to regulate that with new drugs or new cell signalling behaviour that can regulate the number of doors available. Also we’ll try and block up the doors with new inhibitors, which a lot of drugs are, and then even if you have a stroke or a traumatic brain injury, maybe we can stop the water being able to get through those doors, get through those aquaporins and block some of this brain swelling and then hopefully block some of the dangerous effects of the swelling.

Sam: So it’s kind of staggering the speed at which these proteins move.

Alex: Actually blocking it completely, reducing the ability of the water because it takes hours for the brain swelling to happen clinically if you have one of these problems. And if we can just stop that happening we’ve got more time to stop the brain swelling and get to the site of injury.

Sam: So would this only be for injuries that aren’t say a direct impact of the head?

Alex: Yeah, absolutely. For example, if you have a stroke this can be a slight ischemic response, which means not very much oxygen to a certain part of the blood vessels in the brain and this stops the energetic processes working in the brain and therefore stops, causes water to come in through aquaporin 4 and cause exactly the same brain swelling that we see in traumatic brain injury. We also get oedemas elsewhere – pulmonary oedemas, kidney problems, cellular oedemas – anywhere where water has to move in large amounts, they move through one of the aquaporins. There’s thirteen in humans, thirteen different types, and they all seem to be regulated and we’re studying all of those regulations to see if there are potential therapeutics in the future there.

Sam: How would we be able to regulate these aquaporins?

Alex: This is exactly what my research group is working on right now up in the lab in the Medical School. We’ve shown that, for example, having calcium outside the cell is essential for these aquaporins moving about very quickly within seconds. We’ve shown that other proteins, called kinases, these are enzymes which add bits onto the aquaporin 4. These are necessary to move the aquaporin out into the surface, so if we can target those instead of the aquaporin directly, or if we can block the calcium interaction then we might be able to regulate the movement. Similarly, the aquaporin 4 has a hole, it is a water hole, but if we can block this hole with something that isn’t toxic to our bodies then this might simply block the water movement in forming oedema. So we’re approaching this from two angles; one is what’s the shape of aquaporin and can we block that? One is how is aquaporin regulated by other parties, other partners, and can we block them or interrupt them or somehow effect them to stop this happening, or to promote it happening but somewhere else in the cell? So that’s what we do in our group. 

Sam: So this isn’t the only protein you’re working on in your research group is it?

Brandon: That’s right. I am lucky enough to have received a grant from the British Heart Foundation, so those red shops in the high street, and they’ve funded us to look at another membrane protein, kind of similar to aquaporins, but these are thought to be involved in heart disease, they’re thought to be protective for heart disease and our job is to try and spot a drug binding pocket at the surface of the cell that will allow medicinal chemists or the pharmaceutical industry to take this forward in the future and create drugs that might help with heart disease. 

Sam: Fantastic. Well I look forward to hearing the results of that one when you finally reach the conclusion. So, Brandon Ashinoff, thank you very much for joining us today.

Brandon: Thank you.

Outro VO: This podcast and others in the series are available on the Ideas Lab website: There's also information on the free support Ideas Lab has to offer to TV and radio producers, new media producers and journalists. The interviewer and producer for the Ideas Lab Predictor Podcast was Sam Walter.