Allison Cowin will lead off the session with her group’s latest findings on the regulation of cellular adhesion and migration during wound repair. Cowin hails from England originally, where she did her PhD and postdoctoral training at the University of Manchester. In 1996, she saw the light and headed for Australia, where she now runs the wound healing group at the Women’s and Children’s Health Research Institute in Adelaide.

Cowin’s overall research aim is to understand the mechanisms involved in wound healing and scar formation. A lot of the players involved are known, but how do they all work together at the cellular and signalling level as cells migrate and fill in a wound site, and what are the best targets for therapy?

The goal for Cowin and for the field in general is to develop new therapies for wounds and burn injuries. Currently, no effective mechanism-driven products exist for countering wound healing-related health problems: that is, something that will make the cells do a better job.

Treatments still rely on bandaging and compression measures, and just trying to stop the associated tissue oedema from taking over. So, there is a huge market out there for something that would work to fix or alleviate the problem from the source.

The major applications for this work are to make chronic wounds heal and to reduce scarring in burns and other injuries. Chronic wounds tend to be something that people don’t think about but they are an increasingly large problem in our society, particularly in the elderly and in patients with diabetes.

“They get these wounds that just will not heal,” Cowin says. Chronic wounds and scarring are really two sides of the same coin, and the same molecules are probably regulating both.

Cowin has wanted to know what regulates wound healing for many years. She is interested in the mechanisms behind cells migrating to and repopulating a wound site under different physiological and pathological conditions.

“We knew already that the cytoskeleton was important in this whole process, in the ways cells travel into a wound and in bringing the wound margins together to re-epithelialise the site,” she says. In particular, Cowin was looking at the roles of actin and actin-remodelling proteins such as gelsolin and paxillin, which are important mediators of cell adhesion and migration.

As is often the case, a serendipitous conversation (and subsequent collaboration) with some scientists at the Australian National University in Canberra turned Cowin’s attention to a cytoskeletal protein she had previously not investigated. Called Flightless I (Flii), it belongs to the same family of actin-remodelling molecules as gelsolin.

“So, I looked at it in our experimental systems, and it now turns out that Flii might be more important than any of the other family members in the wound healing process.”

Using some transgenic and knockout mouse models from the ANU labs and an incisional wounding assay, Cowin identified Flii as a negative regulator of wound healing, with the findings published in the Journal of Pathology in 2007.

Over-expression of Flii impaired the healing process, while knocking it down made the incisions heal much better. “It was quite a fundamental discovery, that this important protein is actually a bad guy in wound healing. Since then we have been designing methods to reduce its activity within a wound in the hope of improving wound healing.”