Dufour Lab to investigate the biological role of calpain 3 in muscle

Coalition to Cure Calpain 3 (C3) is celebrating the New Year with a new research grant! We are pleased to announce a grant has been awarded to Dr. Antoine Dufour, Assistant Professor of Physiology and Pharmacology at the University of Calgary. The project, titled ‘Unbiased Systems-wide Investigation of Calpain 3 in Patients with LGMD2A/R1 Using Mass Spectrometry,’ aims to better understand the biological role of calpain 3 in muscle.

Calpain 3, the protein that is missing or defective in LGMD2A/R1, belongs to a class of proteins called proteases. Proteases have the ability to cleave other proteins. Dr. Dufour’s project aims to identify the proteins cleaved by calpain 3. To do this, his team will use a technique called mass spectrometry to screen all of the proteins present in muscle cells to identify which are cut by calpain 3. Muscle samples from LGMD2A/R1 mouse models and patients will be analyzed. Screens will also be performed to identify changes in protein expression and the role of calpain 3 in signaling to other proteins. This project has the potential to help the scientific community more fully understand the biological function of calpain 3, and how its dysfunction leads to LGMD2A/R1.

C3 Scientific Director Dr. Jennifer Levy comments, ‘We do not yet have a full understanding of the biological role of calpain 3 in skeletal muscle. Dr. Dufour’s study has the potential to increase our understanding of which proteins calpain 3 acts on in healthy muscles, and why calpain 3 absence causes muscular dystrophy. Further, the proteins identified in this project could serve as biomarkers of disease or as druggable targets for treating LGMD2A/R1.’

Dr. Dufour says, ‘Our unique technique (N-terminomics/TAILS) allows for the identification of the cut ends of proteins cleaved by calpain 3 by selectively purifying them from the rest of the proteins, therefore, making it easier to find the needle in the haystack. The identification of these segments cut by calpain 3 will help to understand the faulty mechanisms involved in LGMD2A progression. Using our unbiased and system-wide analyses, we will further characterize the development of LGMD2A and we will elucidate the disease mechanisms underlying LGMD2A.’

Click here for the Dufour Lab’s twitter feed