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'Flightless' protein helps heal wounds

Professor Allison CowinProfessor Allison Cowin

25 June 2009

Under normal conditions, our skin has amazing powers of healing. But in extreme cases such as traumatic or burns injuries, we often end up with horrific scarring, disfigurement or even disability.

In trying to determine the molecular mechanisms involved in healing skin, Associate Professor Allison Cowin and her team at the Wound Healing Laboratory in Adelaide focused on a cytoskeletal protein called ‘flightless’. To their surprise, they found that reducing this protein’s activity improved wound repair.

In this podcast, Assoc Prof Cowin explains to Dr Andi Horvath how the flightless protein got its name and how its antibodies may provide a new therapy for healing wounds.

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Transcript of podcast

Voice-over: Welcome to this special National Health and Medical Research Council podcast on Ten of the Best Research Projects for 2008. Our podcasts aim to keep you in touch with major health and medical research issues and the people who shape them.

Introduction: Hi I’m Dr Andi Horvath and I have the pleasure of interviewing Associate Professor Allison Cowin. She’s the head of the Wound Healing Laboratory at the Women’s and Childrens Health Research Institute in Adelaide.

Interviewer: Congratulations to you and your research project team. Allison, give us a small précis of how wound healing works.

Assoc. Prof. Cowin: Well wound healing as you can imagine is a very complicated process with many overlapping phases. We get an initial inflammatory phase, which is then followed by the phase where the wound edges have to come together, which is called re-epithelialisation, and then finally we get a phase where remodeling occurs when all the collagens have to be remade underneath the skin so that we don’t get a scar from occurring. And all those processes are regulated by the cytoskeleton which is the area of research that we are very involved with.

Interviewer: Now wound healing and proper wound healing is really important for all sorts of injuries in terms of burns right through to accidents simply because the skin is our major line of defence against infection, is that right?

Assoc.Prof. Cowin: That’s correct, it’s the largest organ in the body and its major role is, as you say, to keep us safe from all those horrible little pathogens and micro-organisms which are out there. But like you say, there’s a whole range of different wounds that we can get, ranging from the burns injuries right up to the chronic wounds, which are an important area for the elderly and people with diabetes. And they happen to have skin which just doesn’t want to heal, so they’ll end up with open weeping sores on their lower legs and feet and it’s incredibly painful for them. I think as our society ages and we get more obese people and more diabetic individuals we’re going to see many, many more wounds occurring and it’s going to be a much more significant issue for the whole population.

Interviewer: Take us back in time. What was the premise of your investigation that formulated your research directions?

Assoc. Prof. Cowin: Well what we knew was that under normal conditions our body has an amazing ability to be able to heal itself. I mean we’ve all cut ourselves and we’ve all fallen over and our body has been able to repair itself so often you can’t even see where the original injury had occurred. But in many situations such as in response to a trauma or a burns injury, the body just cannot meet the challenge and you often end up with horrific scarring and disability and disfigurement and this is of particular importance in children who are still growing. So we are really keen to try to understand the mechanisms that are involved in wound healing so that when it goes wrong we can potentially put it back on the right track. And I guess we’re interested in learning how the cells actually work and all of our cells contain a cytoskeleton. And a cytoskeleton is really just similar to the skeleton that we all have in our body, which gives us structure and support and allows us to move, but the cytoskeleton in a cell allows it to be able to migrate and proliferate which is key processes in wound repair. So what we wanted to do was to try and understand the role of the cytoskeleton in wound healing.

Interviewer: Allison, what aspect of wound healing did you focus in on? Did you go right down to the molecular level? What was the approach?

Assoc.Prof. Cowin:  Yes, we were very interested in trying to determine the molecular mechanisms involved in wound healing, so looking at how cells can actually proliferate and adhere, because these are key processes in how a wound is able to re-epithelialise and heal itself. So we were interested in the proteins that are involved in the cytoskeleton and one of these proteins which we identified was called ‘flightless’, and that was the protein that we focused in on this particular project.

Interviewer: So Allison, the name of the protein is ‘flightless’ like a bird, is that right?

Assoc. Prof. Cowin: That’s right. It was first identified by some geneticists who were studying the drosophila. And they identified that if they actually deleted, they mutated this protein, then the flies were no longer able to fly, so they called it flight-less. So we’ve been stuck with this great name for the protein, which has nothing to do with flying in wounds but about how flies can fly.

Interviewer:  Associate Professor Allison, what were the research outcomes of your investigations into the flightless protein and the cytoskeleton structure of the cell? What was the end result of all this research?

Assoc. Prof. Cowin: Well we actually were very fortunate to be able to use some transgenic mouse models, so we were able to over-express this gene and were able to knock it out by about 50% to be able to look at how we can actually reduce the levels. And we found quite surprisingly that decreasing the expression of this protein actually improved wound repair and this wasn’t what we were expecting, so we were quite excited about this. And we also found that this protein was actually secreted in response to wounding and that was totally novel and unexpected. But this actually allowed us to be able to potentially make antibodies, which can actually neutralize the activity of the protein, and we’ve developed a whole series of antibodies which when we apply them to the wounds, we can actually knock out this protein and the wounds heal much better.

Interviewer: Are you actually using this antibody knock-out right now to heal wounds?

Assoc. Prof. Cowin: Well not in patients so far. We are still at the very early stage, but what we have been able to do is to make these antibodies and put them into our mouse models and find that our wounds heal much, much better. And we’re currently developing some more specific antibodies, some monoclonal antibodies, which we can see is a route to a new therapy that we might be able to take to the public in five to seven years time.

Interviewer: One of the questions you probably get asked by a couple of people is, ‘Why do you do this research?’ Because it’s amazingly complex and has long time frames.

Assoc. Prof. Cowin: It is, but it’s incredibly important to be doing something that is worthwhile to me, to be doing research which potentially will improve patient care and improve clinical outcomes. I personally don’t particularly want to be doing research just for the sake of answering a research question. I want to be doing research which will help the public in the future. So that’s what motivates me. I see these patients with horrific burn injuries or patients whose wounds just won’t heal and I just want to be able to do something to help them and that’s what keeps me interested.

Interviewer: Allison, introduce us to your multi-disciplinary team, because these types of projects require lots of different types of expertise. Firstly what was your expertise?

Assoc. Prof. Cowin: Well I started doing wound research about 15 years ago now as a post doc in one of the best wound laboratories in the world, in Manchester, and that really got me interested in doing wound research. And I came to Australia in 1996, just for 3 years, just so I could tick on my CV that I’d done my overseas three year visit and go back to the UK, but I just loved Australia so much and the research that we were doing here and there’s some incredible research happening, that I just never went back. So yes, it’s been a good journey for me.

Interviewer: Allison, introduce us to your team members. Who are they and how did they contribute to the project?

Assoc. Prof. Cowin: I was first introduced to Dr Hugh Campbell who is at ANU and he was actually the first person who actually discovered this particular protein in humans. And he had developed these amazing mouse models but didn’t know what it actually did, and because my background was looking at cytoskeletal proteins and their function in wound repair, it just seemed an obvious interaction to make. So we did some preliminary studies and showed that it was potentially important and then we put together the application and with the help of Barry Power who was another CI (Chief Investigator) we found this project worked really well.

Interviewer: Associate Professor Allison, can you recall a research project anecdote that you like to tell colleagues?

Assoc. Prof. Cowin: Well I don’t really have any anecdotes as such, but I think I just might mention the serendipitous nature of science. I mean this project would never of happened if it hadn’t been for a conversation over a coffee with a colleague who used to work with Hugh Campbell at ANU, and if he hadn’t known that Hugh was doing what he was doing and what I was doing, we would never have got together and this would never have worked. So just conversations can lead to such important breakthroughs and potentially lead to totally new treatments which might never have happened.

Interviewer: Allison, some final reflections on being a chief investigator. Will you do it all again and why?

Assoc. Prof. Cowin: Oh I absolutely will do it all again and I’ve just got an NH&MRC project grant to continue the work that we’re doing, and also a development grant to continue the development of the antibodies. So I’m keen to keep going with this line of research I think it’s very worthwhile and very exciting.

Interviewer: Thank you. We’ve been talking to Associate Professor Allison Cowin who is the head of the Wound Healing Laboratory at the Womens and Childrens Health Research Institute. She was also a Chief Investigator in an NH&MRC project. Good luck with your next adventures Allison.

Assoc. Prof. Cowin: Thank you.

Voice-over: This podcast was brought to you by the National Health and Medical Research Council, working to build a healthy Australia. You'll find more information about this and other health and medical research issues on our website at www.nhmrc.gov.au.

Page reviewed: 7 April, 2011