Research group of Dr Angus McQuibban

Research group of Dr Angus McQuibban

from left to right, Jarungjit Rujiviphat, Jeffrey Lee, Silvia Pagoada-Vallecillo, Angus McQuibban, Eliana Chan, Natasha Frick

Dr Angus McQuibban is a principal investigator in the Department of Biochemistry at the University of Toronto. Research in the McQuibban lab focuses on the molecular mechanisms of mitochondrial membrane dynamics and their relation to cell function.

Angus studied his M.Sc. with Peter Lewis at the University of Toronto and then went on to complete his Ph.D. at the University of British Columbia with Chris Overall. Following a successful characterization of extracellular proteases, Angus decided to extend his expertise in protease biology by moving to the Laboratory of Molecular Biology (LMB) and conducted his Post-Doctoral Fellowship under the guidance of Matthew Freeman, with fellowship support from the European Molecular Biology Organization, the United Mitochondrial Disease Foundation, and the Natural Sciences and Engineering Research Council of Canada. It is at the LMB where Angus made his key discovery that a novel mitochondrial protease, called rhomboid, regulates cell life by controlling mitochondrial membrane dynamics.

Angus’ team hopes to determine the protein machinery that orchestrates and regulates mitochondrial membrane dynamics, particularly fusion. On a broader scale the team hopes to understand the biological significance of dynamic mitochondria and the consequences of disrupting this process in relation to human mitochondrial diseases. Angus uses Drosophila melanogaster as a model organism to investigate the dynamic behavior of mitochondria which is something that has not previously been pursued in this model organism. The reason for the dynamic behavior of mitochondria is not currently known; however disruption of these mitochondrial dynamics can result in diseases such as Dominant Optic Atrophy and Charcot-Marie-Tooth type 2A disease.

Previous studies have identified only a handful of factors that are involved in regulating mitochondrial membrane dynamics. Through his research Angus hopes to answer two fundamental questions.

  • What role do mitochondrial dynamics play in cell and tissue function?
  • What molecular machinery is required to orchestrate and regulate mitochondrial double membrane fusion?

In order to help advance this research Angus uses the latest fluorescence techniques to image mitochondrial dynamics as they happen using live tissues and cells. GFP (the molecule that won the 2008 Nobel prize in Chemistry) is integrated into the mitochondria of flies that are mutant for many genes that are thought to regulate mitochondrial dynamics. By imaging these molecular processes directly in live cells, Angus and his team can dissect out the mechanisms that regulate this biologically important process.

Angus uses Volocity exclusively to image these events. Angus says “I find Volocity to be the most user friendly and intuitive software program available. In addition, the power and ease of data management and presentation, especially 3-dimensional reconstructions, makes Volocity the best imaging package for our applications.”

Please visit the McQuibban lab to learn more about Angus' research.

 

During fly spermatogenesis, all of the mitochondria in the sperm cell come together and fuse into a giant mass called the nebenkern. They appear as spherical structures, similar to a billiard ball, shown here is a snapshot of a 3D reconstruction of localization of the OPA protein to these mitochondrial derivative called the nebenkern (~40 cells are shown). The GFP fluorescence shows that the distribution of OPA is not even throughout the nebenkern, but is found in peaks and valleys in the structure, likely areas where membrane fusion is the most active.