Refine, Reduce and Replace the use of animals in research

As the largest human organ in the body, skin is a major reservoir for bacterial invasion and infection. As such, skin infections are the fourth commonest cause of all human disease, effecting almost 900 million people in the world at any time.

There is a current lack of suitable research models to fully understand the complex mechanisms of skin infections. Group A Streptococcus (GAS) is a bacterium that causes severe skin diseases and is a major contributor to the global burden of infectious diseases. 

The precise molecular mechanisms of the development of GAS skin infections are still largely unknown. The majority of studies into GAS infection heavily rely on the use of animal models, however they fail to fully recapitulate human physiology and in particular, human skin. Thus, efforts in developing potential GAS treatments have been significantly hampered. 

“We saw a real need for a more biologically relevant skin infection model, as well as the need to move away from animal testing,” said Dr Diane Ly who was this year’s recipient of the 3Rs grant, aiming to refine, reduce and replace the use of animals in research. 

“Not only is it ethically preferable not to use animals such as mice in our research but this new in vitro model will better mimic the clinical condition by using human skin cells. I am very passionate about reducing the need to use animal models in research, and believe that this model will provide a better understanding of the mechanisms involved during GAS infection in a more clinically relevant environment, and potentially reduce the need to use animal models,” said Dr Ly. 

The Chair of the UOW Animal Ethics Committee, Dr Malcolm France, has commended the University for its 3Rs Research Grant initiative. 

He said “To the best of my knowledge, UOW was the first university in Australia to initiate an independent funding program specifically to support research with the potential to replace, reduce or refine the use of animals in research.” 

Dr France said there are still important research questions that can only answered by studying animals. He noted, however, that the community rightly expects the scientific community to seek alternatives to animals wherever possible and that the regulatory code actually requires this. 

“I am hopeful that UOW’s lead in this area will encourage other institutions to offer similar support for researchers interested in finding replacements to the use of animals in research,” he said. 

Dr Ly’s work will build on the 3D skin in vitro culture model system developed at Swinburne University by the team’s collaborators Prof. Sally McArthur and Dr Aleta Pupovac. 

“I will be visiting Professor McArthur’s team at CSIRO to learn how to build the 3D human skin model, and adapting it here at UOW to establish and characterise the world’s first human 3D organotypic GAS skin infection model to better understand GAS virulence in a more relevant (human skin) environment,” said Dr Ly.

To date there have been no studies employing in vitro 3D human skin models to study streptococcal skin infections. 

“There are successfully established models to study mechanisms of infection by Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii, but to our knowledge none for GAS skin infections.” 

Being able to change or manipulate the model to test for other infections will significantly contribute to reducing animal testing in research and will help researchers understand (and treat) diseases more effectively. 

“The data generated from this work will be new and will significantly contribute to our research field. We will also be able to use this model to expand projects within our research team including investigating the formation of bacterial biofilm communities in GAS-infected skin wounds, which are becoming a major concern in clinical settings due to their high resistance to current antibiotic treatment.” 

Researchers involved in this study are: 

Dr Diane Ly and A/Professor Martina Sanderson-Smith SCMB in SMAH and affiliates of IHMRI and Molecular Horizons.
Prof. Sally McArthur and Dr Aleta Pupovac are from CSIRO and Swinburne University of Technology.