Leading scientists from Biomedical Proteomics and Bioinformatics at CMRI contributed to a recent article that advanced understanding of dysferlinopathy, a progressive muscular dystrophy disease. The study was led by Dr Frances Lemckert at the Kids Neuroscience Centre, The Children’s Hospital at Westmead. 

Dr Lemckert’s team use CRISPR/Cas9 gene editing to knock out murine Dysf exon 40a, to specifically assess its role in membrane repair and development of dysferlinopathy. Proteomics and Bioinformatics analysis at CMRI compared each mouse line, identifying and quantifying thousands of proteins, to show all three 40a knockout (KO) lines (with protein expression ranging from ~10%-90%) are spared the profound proteomic imbalance that characterises dysferlin-deficient BLAJ muscles. 

Collective results indicated that ~ 10–20% of wild type (WT) dysferlin protein expression is sufficient to maintain the muscle lipidome, proteome and membrane repair capacity to crucially prevent development of dysferlinopathy. Thus, a small restoration of dysferlin function in dysferlinopathy patients may have profound effects, offering hope that future treatments might be successful if they can meet this threshold. This study used a streamlined proteomics and bioinformatics workflow that is available to our customers to help accelerate their research goals.

Read the full article* here, and if you are interested in accessing our Proteomics and Bioinformatics services, contact Josh Studdert, CMRI Research Facilities, e: jstuddert@cmri.org.au, m: 0419 175 521.

*Joe Yasa, Claudia E. Reed, Adam M. Bournazos, Frances J. Evesson, Ignatius Pang , Mark E. Graham , Jesse R. Wark , Brunda Nijagal , Kim H. Kwan, Thomas Kwiatkowski, Rachel Jung, Noah Weisleder, Sandra T. Cooper and Frances A. Lemckert (2023) Minimal expression of dysferlin prevents development of dysferlinopathy in dysferlin exon 40a knockout mice. Acta Neuropathologica Communications 11:15