UQ Research Update
Brad Launikonis talks about the hard work at the University of Queensland’s Muscle Research Lab and further exciting developments. Firstly, I wish to thank all of you who have given us initial permission to access muscle biopsies for the purposes of our research into muscular dystrophy. We are very grateful for this and to Muscular Dystrophy Queensland for making the announcement to you all on our behalf. We are currently working across three institutions (Royal Brisbane Hospital, University of Queensland (UQ) & La Trobe University in Melbourne) to gain ethical approval to access the stored biopsies. This is necessary because both my laboratory at UQ and my collaborator at La Trobe University (Dr Robyn Murphy, an expert muscle biochemist) will be involved in working on the biopsies. When we have this clearance, a member from Muscular Dystrophy Queensland will bring a release form for you to sign, giving us the final ‘go-ahead’ to access the biopsies. We will only require a very small portion of the biopsies, leaving the majority of tissue in storage at the hospital for future work. We are very excited about the information your biopsies may present to us.
We have just published a paper on muscular dystrophy, which appears in American Journal of Physiology-Cell Physiology in the July issue. This is mainly the work of Dr Josh Edwards in my lab in collaboration with Dr Murphy. We compared a regulatory pathway in healthy mouse muscle with that in the mdx mouse, a model of muscular dystrophy. We found the proteins involved in the regulatory pathway to be increased 3 times in the mdx mouse and we think that this could be the mouse compensating for its dystrophic state to improve its muscle function. This leads us to our next project and the request for biopsies.
Because muscular dystrophy is a genetic disease, attempts are being made to develop ways to deliver a dystrophin gene to patients. One of the major problems is that the dystrophin gene is too large to fit in the vehicle used to deliver it to the muscle, which is a virus. Investigators in this field are attempting to ‘shorten’ the gene so that it packs into the virus and can be delivered to the muscles. Such work has been achieved in mouse but the benefits in terms of muscle function were not a good as hoped. Work continues in this area.
We wish to provide complimentary strategies to the delivery of the shortened dystrophin gene to the muscles. By identifying genes of other muscle proteins that can improve muscle function we hope that they can be delivered in conjunction with the shortened dystrophin gene for a better outcome, however much work is in front of us to show that other non-dystrophin genes will improve muscle function. Final implementation of our work will require other labs around the world to continue to develop the techniques of delivering genes with viruses, which has only been achieved in mice and other small animals to date.
The biopsies that you have kindly granted us access to will allow us to measure the levels of proteins in human muscle and compare them against those in the mdx mouse that we identified as important in our new paper. Because we believe the mouse is unique in its ability to increase production of muscle proteins to compensate for the decreased function in dystrophy, this makes it useful in identifying potential therapeutic targets for dystrophy. In conjunction with Dr Murphy, we will make these measurements. This is essential to identifying that the mice are indeed increasing the levels of these proteins to improve muscle function and offset the dystrophic state.
Next we will gain the technology to deliver genes to mouse muscle. Ms Tanya Cully, a PhD student in the lab, will be travelling to Melbourne soon to work with one of the experts in the field of delivering genes to muscles with viruses. This is difficult work we expect to take some time. I expect her to be there for several months. Upon arriving back in Brisbane with this technology Tanya will deliver the genes we have identified to mice to potentially improve muscle function in dystrophy. Tanya will then rigorously test the function of muscles of the mice she has delivered the gene to. We are very excited about the prospects of this work and thank Muscular Dystrophy Queensland for supporting this project.
We also welcome Ms Keira Burlinson, as a new PhD student in the lab, who will work on aspects of this project as well. We are teaching her techniques used in the lab to study muscle function at present. We are very pleased that Muscular Dystrophy Queensland has chosen to support her with a scholarship so that she may pursue research in muscular dystrophy.
On behalf of Robyn, Josh, Tanya and Keira, thank you once again and we look forward to keeping you informed on our research.