The 4th annual AWTRS conference was opened with a welcome from society president Dr Rachael Murray on Sunday afternoon the 4th of May at the Gold Coast Convention and Exhibition Centre in sunny Queensland. We launched straight into the first of the three days, hosted by QUT and the Institute of Health and Biomedical Innovation with a MasterClass session chaired by Dr Leila Cuttle which gave us a glimpse of the future of wound and tissue repair research. Presentations by 6 doctoral candidates or early career researchers demonstrated the breadth of research undertaken within the field, from lab bench to bedside. Research which ranges from understanding microRNA involvement in keratinocyte migration and intracellular trafficking within macrophages, through the characterisation of the wound healing phenotype of various mouse strains and cytokine profiling of chronic leg ulcers, all the way up to development of wound healing therapeutics from native plants and clinical trials of low dose aspirin as an adjunctive therapy in treating chronic ulcers. We certainly look forward to hearing more about the progress of this research at the next meeting!
The second Masterclass was a panel discussion with Prof Carien Niessen, Prof David Becker, Prof Rick Sturm and Dr Leila Cuttle, chaired by Associate Prof Sue McLennan who neatly summarised the careers of the speakers into key points which were helpful tips for students and early career researchers just beginning the journey. We were told to look for work in labs which fitted our personalities and that it helps to have colleagues who ‘laugh as loud as you do’. We learnt that a successful career may come from finding the right fit and staying there for a long time, or it may require making a big change and going where opportunities arise. We heard about the importance of international collaboration and taking time to learn from those who are experts in the field to improve your own research and finally that if you can’t research in an area which traditionally draws a lot of funding, make sure you are passionate about what you do and see the positive impact that you can make upon the lives of many via the improvement of wound care. The panel highlighted the importance of finding mentors to help you along the way and that fundamental to developing these relationships was networking at meetings such as this one.
Day one was concluded with a poster session and welcome reception, accompanied by hors d’oceurvres and wine, where a larger number of posters were presented by the society’s young researchers, presenting data showcasing their doctoral research. Following their poster presentations the students and ECRs had a great opportunity to practice their networking skills at the ECR social event held on this first night of the conference within Jupiters Casino where a free drink helped to open the lines of communication. There was much open discussion of research and exchange of ideas and email addresses, in an informal atmosphere where new relationships could be formed.
Day two began with the first plenary lecture by David Becker and chaired by Rachael Murray. Prof Becker described the development of a promising new treatment to promote the healing of chronic wounds by targeting the gap junction protein, Connexin 43 through the application of Cx43 specific antisense gel to diabetic and venous ulcers. The day’s first session ‘Mechanism of repair and fibrosis’ was chaired by Leila Cuttle and begun with Rob Parton from the Institute of Molecular Bioscience giving insights into the ‘little caves’ or small invaginations of the plasma membrane that are called caveolae and seen in many cell types. These lipid structures are formed and maintained by caveolin proteins and enriched with signalling molecules. Genetic ablation of caveolin proteins is associated with a number of muscle diseases. Parton showed in his presentation that cellular mechanoprotection is achieved by the disassembly of caveolar rosettes. Polarised distribution caveolin proteins and caveolae also suggest that they play a role in directed cell migration. Allison Cowin from the Mawson Institute and former president of the AWTRS presented data showing that Flightless I (Flii) is a potential target for the development of anti-scarring treatments due to the impact of this protein as negative regulator of hypotrophic scarring. Anti-Flii antibodies have shown to reduce scarring. If the seen effect is due to neutralisation of the secreted or intracellular form of Flii is yet unknown but could arise from the proposed link between intracellular Flii and regulation of pro-scarring TGFβ1 expression.
A mathematical model developed from cell culture experiments was presented by Matt Simpson from QUT and proved to accurately predict the position of the leading edge of a moving cell front – a feature essential of wound repair and cancer metastasis – and cell density profiles based on random motility and proliferation. Jemma Evans from Prince Henry’s Institute educated us about the rapid scar-free post-menstrual repair of the endometrium. Factors involved in this process seem to act in a paracrine manner to facilitate repair and have also shown to promote re-epithelisation in wound healing models of in vivo and ex vivo assays. Using a proteomic approach combined with functional assays Evan’s group was able to identify specific factors of menstrual fluid involved in the rapid re-epithelisation. Using a whole muscle autograft model of muscle regeneration Eleanor Mackie’s group at the University of Melbourne showed that skeletal muscle regeneration requires signalling via protease-activated receptor-1 (PAR-1) and that PAR-1 null muscles exhibit decreased numbers of neutrophils and macrophages and increased fibrosis of the tissue.
The second plenary speaker, Graham Lieschke from Monash University, talked about his studies of leukocyte behaviour in response to sterile wounding using an in vivo zebrafish model. Performing live imaging, he showed that neutrophils arrive at the wound first and can cell-autonomously down-regulate the post-wounding hydrogen peroxide gradient. This migratory behaviour could be altered by modifying the hydrogen peroxide gradient, which could explain defective leukocyte migration in situations of perturbed hydrogen peroxide dynamics after wounding. Prof Lieschke also showed that macrophage migration towards the wound site is slower than neutrophil migration but that macrophages remain at the wound margin for longer than neutrophils.
Rachael Murray, current president of the AWTRS, chaired the next session on ‘Inflammation, wound healing and regeneration’. The session started with the presentation of Chris Jackson from the Kolling Institute who showed us that activated protein C (APC) utilises Tie2 enhance endothelial barrier function and maintain blood vessel integrity in mice. As APC reduces the vascular permeability also fewer cells can infiltrate the surrounding tissue. The next speaker, Megan Lord from the University of NSW, presented her work on perlecan, which is a large multidomain heparan sulphate proteoglycan of the extracellular matrix that binds with high affinity to platelet factor 4 (PF4). PF4 itself gets released from the α-granules of activated platelets and acts as chemotactic for neutrophils, fibroblasts and monocytes and thus, plays a role in inflammation. Perlecan inhibits platelet activation by binding and controlling the activity of PF4 and through this binding exhibits an anti-inflammatory role by mopping up PF4 to prevent downstream signalling events that promote the on-going inflammatory response.
Coming all the way from the University of Otago in New Zealand Lyn Wise suggested an inhibitory role for Langerhans cells (LCs, epidermal dendritic cells) during cutaneous wound healing. She showed that depletion of said LCs improved wound closure and decreased the numbers of DCs while increasing the numbers of macrophages and cytotoxic T cells. This could mean that LCs may suppress the proliferative phase of cutaneous wound healing by modulating trafficking of immune cells. The session was completed by the presentation of Danqing Min from the Royal Prince Alfred Hospital. In her project, she analyses the profiles of circulating monocyte (CD14+) and their subsets (CD16+/-) in Diabetic foot ulcers and aims to correlate the observed changes of the circulating monocyte profiles to potentially predict wound healing outcomes.
Following lunch conference delegates were treated to two sessions covering all aspects of chronic wounds. Prof Sue McLennan and her research team from the University of Sydney gave us an update of their research investigating matrix metalloproteinases and their role in diabetic wound healing, including Prof McLennan’s doctoral student Tara Ng whose research has focused particularly on the role of MMP-9. Flavia Huygens from Queensland University of Technology presented her work her work to date in understanding microbiome environment of chronic wounds. The final presenter of the session was Jessica Sutcliffe, a doctoral student from Prof Becker’s lab. Jessica’s presentation followed on from Prof Becker’s plenary presentation, focusing on the expression of gap junction proteins, connexin 26, 30 and 43, their presence in chronic wounds and role in keratinocyte migration.
The second session on chronic wounds following afternoon tea was patient outcome orientated, hearing a number of presentations on various treatments currently being investigated for the treatment of chronic wounds. Dr Melissa Fernandez took us through her research and preliminary clinical trial progress into the use of topical allopurinol for the treatment of chronic venous leg ulcers, and Dr Claudia Rutherford from the University of Sydney gave us an insight into the quality of life of patients who live with pressure ulcers. The final talk of the day was from doctoral student Daniel Broszczak who took the audience through this research which uses mass spectrometry techniques to analyse wound exudate and swabs from chronic wounds in the aim of discovering biomarkers indicative of healing wounds.
The conference dinner was held at the Sofitel Gold Coast, where conference delegates were treated to a delicious three course meal. During the dinner the society’s travel awards were awarded to doctoral students and early career researchers, this year Dr Tara Fernandaz received an award to attend the 2014 European Tissue Repair Society Meeting in Edinburgh along with visiting “……’s” lab. Two national conference travel grants were also awarded to ….. and ….. to attend the 2014 Cutaneous Biology Meeting. Following dinner the room lights were turned down and the music turned up and the conference delegates danced away for the rest of the night
The final day of the conference was underway with a plenary from Prof Caren Nissen. Prof Nissen’s plenary session extensively covered her research into cell polarity and its role on cell fate and signalling. It was a great segue into the seventh session of the conference ‘Skin biology and cellular regeneration’. The first speaker of the session was Prof Rick Sturm from the University of Queensland gave an overview into his group’s genetic research on melanoma. Rick’s research group, Melanogenix, have studied the factors responsible for melanomas. His presentation mainly focused on complement of pigmentation and person’s specific single nucleotide polymorphisms. The following presentation was by Prof Pritinder Kaur from the Peter Mac Centre which delved more into the cellular environment of wound healing. Her group has found the important role of pericytes which not only differentiate into most cells but also secret important extracellular matrix components which are important in promoting wound healing. The next speaker in the session, Dr Tarl Prow, took us back to the topic of skin cancer. Queensland is the skin cancer capital of the world and Dr Prow’s team has developed an innovative device to take micro skin biopsies using a spring loaded lancet system with multiple needle probes. The scenario described was that this device could in the future be mailed to patients to peform biopsies themselves and send the samples directly to the clinic for analysis.
Dr Rodney Dilley from the University of Western Australia presented current scientific knowledge of the repair process of the tympanic membrane. The membrane is a delicate structure separating the external ear from the middle ear and if perforated can take a long time to heal. The current treatment for these hard to heal membranes is silk fibroin myringoplasty grafts which promote the closure through increased cell proliferation and migration. The final talk in the session was by Mrs Xanthe Strudwick who presented the next chapter in the Flightless I (Flii) protein story. She presented preliminary data which demonstrated that 40% of mice that had overexpressing Flii could regenerate a proximal amputation compared to none in the wild type group. She hypothesised that Flii might play a role in the switch from reparative wound repair to regenerative. The great diversity of the session was capped off by the plenary speaker Prof Mike Philpott which was the first presentation on the science of hair follicles. Mike is a very charismatic speaker who had a wonderful story to share about how he developed the first culture of hair follicles in vitro. This culture method was the first time hair follicles had been grown in cell culture flasks which opened the door into the research of hair loss. The method is still used to date and has helped answer several questions about hair cell cycles, metabolism of follicles and potential therapeutic targets.
The first speaker of the ‘Cells and Tissue Engineering’ session, Prof Anthony Weiss, summarised a vast amount of his team’s work which focused on 3D fabrication of scaffolds devised from the protein tropoelastin. The protein itself as the name suggests has elastic properties which allow it to be easily shaped and capable of withstanding stress applied to it. The human protein is well tolerated and could potentially be used for multiple tissues targets, including the skin, ligaments and arteries. Dr Jacqui McGovern presented her recent work in corneum thickening in the human skin reconstruct (HSR). This thickening greatly reduces the amount of time the HSR can be used in experimentation. Several kallikreins were identified as being key players in the role of the thickening process and might be targeted in future work. Dr Shiva Akbarzadeh reported on the proof of concept work that her team is working on in developing a human skin equivalent to treat burns. This involved the culture of the patients own keratinocytes and fibroblasts for implementation on the burned areas following expansion of the cells. The preliminary data was promising and may provide a novel way to help burn wounds close. The final talk of the session was by Mr Christian Aloe who investigated two natural products for their anti-inflammatory capabilities. This was coupled with the new delivery mechanism of using nano‑particles. In combination these treatments in vitro showed a reduction in pro-inflammatory pathways.
Professor Nicolas Voelcker introduced the Biomaterials session by presenting his work on porous silicon as a means of delivering personalised chronic wound treatments. He was then followed by three talented ECR podium presentations. The first was by CSIRO researcher Dr. Megan Osmond who talked about her research into nanoparticle safety, particularly zinc nanoparticles found in sunscreen. Dr Brooke Farrugia then presented data on her ongoing work exploring the mechanisms through which mast cells respond to implanted materials. Dr Tara Fernandez concluded the session with her talk on plasma polymerisation of wound dressings in order to promote cell migration and proliferation, and therefore healing, in superficial wounds.
The final session of the conference focussed on parallels between cancer and wound healing. Associate Professor Nick Saunders began the session with an interesting talk about the E2F transcription factor and its complex involvement in squamous cell carcinomas. Miss Lipsa Mohanty then presented some of her ongoing PhD work investigating the potential role of the epithelial to mesenchymal transition process during wound healing using a human skin reconstruct (HSR) model. Dr Roberta Mazzieri then went on to speak in depth about Tie-2 expressing macrophages in tumour angiogenesis, growth and metastasis. The final talk of the day was presented by Associate Professor Kiarash Khosrotehrani and focussed on Sox18 and the hierarchy of endothelial progenitor cells during angiogenesis.
Dr Rachael Murray concluded the day by announcing the recipients of prizes for the best ECR podium presentations and posters. Congratulations went to Xanthe Strudwick (University of South Australia) and Jessica Sutcliffe (University College London), who were awarded first and second places for their podium presentations, and to Joan Röhl and Arnulf Compay (both from Queensland University of Technology) who were awarded first and second places for their posters.
A final thank you to Dr Rachael Murray and the Conference Organising committee for an all-round informative and well-organised AWTRS conference. The next AWTRS meeting is scheduled for 2016 to be held in Melbourne, Australia.