U of T researchers receive funding for projects on muscular dystrophy and gene regulation

Two faculty members at the Donnelly Centre for Cellular and Biomolecular Research have successfully secured funding through the Fall 2023 competition of the Canadian Institutes of Health Research (CIHR) Project Grant program. The program supports researchers across Canada whose projects have the greatest potential, according to international standards of scientific excellence, for making advancements in health. Collectively, Penney Gilbert and Timothy Hughes received more than $2.6M in funding for projects to be executed over the next five years.

Evaluating the nerve-muscle connection as a Duchenne muscular dystrophy therapeutic target

Penney Gilbert, associate professor of biomedical engineering, received funding, along with University of Toronto Mississauga professor Bryan Stewart, for a project using an innovative 3D muscle cell culture system to determine the effects of Duchenne muscular dystrophy (DMD) mutations on the physiology of human muscle and synapses. DMD is a genetic disease impacting muscular tissue in males, eventually leading to loss of mobility and death from cardiac and respiratory complications. The research team will analyze the neuromuscular physiology and structure of human muscle cells grown from healthy and DMD-patient stem cells to improve therapeutic treatments of affected muscular tissue.

Developing a comprehensive and accurate codebook of motifs for human transcription factors

Timothy Hughes, professor and chair of molecular genetics and Canada Research Chair in Decoding Gene Regulation, received funding for a project on elucidating the sequence specificity of more than 1,000 known transcription factors. Transcription factors are proteins that recognize and bind to specific DNA sequences for gene regulation. The Hughes lab found that human transcription factors often have unique specificities that are different from those in other organisms; the research team plans to apply techniques and their computational expertise to determining if known transcription factors exhibit higher specificity than previously thought. This project will be undertaken in collaboration with former Donnelly Centre postdoctoral researcher and McGill University assistant professor Hamed Najafabadi.

Analyzing human C2H2 zinc finger proteins systematically

Timothy Hughes also received funding, along with assistant professor Hamed Najafabadi, for a project using a new technique to measure DNA binding of C2H2 zinc finger proteins. These rapidly evolving proteins comprise one of the largest classes of gene-regulating factors in humans and have the unique ability to bind to DNA sequences that are longer and highly specific. The research team plans to develop computational techniques to determine which fingers of the proteins are used at different binding sites.

"Penney Gilbert and Timothy Hughes are exemplary members of the Donnelly Centre community," said Stéphane Angers, professor and director of the Donnelly Centre. "They are pushing the boundaries of their respective fields through technological innovation and collaboration with other leading scientists. Their funded projects will pave the way for treating genetic disease and deepening our understanding of gene regulation."