York University biology Professor John McDermott, who is the McLaughlin Research Chair in the Faculty of Science, has received funding to explore how gene expression is controlled in the heart.
The total project grant from the Canadian Institutes of Health Research (CIHR) is $661,000, to be awarded over five years. The project, titled “Protein:Protein Networks in Regulation of Cardiomyocyte Gene Expression,” will aim to define the composition of transcription factor complexes involved in heart health and disease.
Transcription factors are proteins that regulate the transcription of genetic information from DNA into RNA. They can work alone, or as a complex with other proteins. By turning genes “on” and “off,” transcription factors make sure that genes are expressed in the right place at the right time and in the right amount. But when they don’t function properly, this can lead to disease-related changes in the heart.
“We already know that dysregulation of gene expression is implicated in heart disease,” says McDermott. “Despite the amazing progress in transcription factor biology over the last two decades, however, we are still in the early phase of understanding the complexity of how multisubunit transcription factor complexes in the heart function as receivers and effectors of pathological cellular signalling.”
McDermott’s team, comprising collaborators from Canada and around the world, will define the makeup of transcription factor complexes in normal heart cells, as well as in heart cells exposed to conditions simulating disease, such as cardiac hypertrophy (when the heart muscle becomes abnormally thick), cell death and the progression to heart failure.
This research will lead to insights concerning which transcription factors are involved in disease progression and how their abnormal function can contribute to heart disease, laying the foundation for future drug discovery and treatment to target specific transcription factor complexes.