Dr. Derrick Gibbings, an assistant professor of Cellular and Molecular Medicine at the University of Ottawa Faculty of Medicine, was published in the most recent edition of the prestigious journal, Nature Cell Biology in an article entitled “Selective autophagy degrades DICER and AGO2 and regulates miRNA activity”.
“Essentially,” explains Dr. Gibbings, “autophagy, which literally means self-eating, is a process whereby the cell can sense and eliminate dangerous or toxic materials from itself. It is a fascinating process that we sometimes portray a bit like PacMan operating in all of the cells in our bodies. In autophagy, the cell creates a large enclosure that swallows up the dangerous or damaged materials, hiding it from the cell until it can be degraded.”
Dr. Gibbings explains that it in the last ten to twenty years, we've recognized that autophagy is an essential process to help cells cope with many types of infection or disease. When the process of autophagy breaks down because of a genetic mutation or a disease, the cell can longer clean itself out and toxic materials accumulate. The cell can longer perform its functions and control its growth. Indeed, defects in autophagy are the cause of some cancers and neurodegenerative diseases such as Alzheimer's disease. The recognition of the importance of autophagy in these diseases has instigated enormous investments from drug companies in activating autophagy to treat cancer and Alzheimer's disease among others.
Dr. Gibbings, together with colleagues from The Swiss Federal Institute of Technology, Institut Pasteur and Imperial College London, believe they have discovered one of the reasons why autophagy has such severe consequences in diseases like cancer. They found that if they inhibited autophagy, mimicking a condition found in cancer cells, that a mechanism of regulating genes and cell functions stopped working too. They found that proteins essential for the activity of microRNA were being degraded by autophagy perhaps to renew and control aged components of the system. MicroRNA are a class of tiny RNA that was recently discovered and is known to regulate many processes in the body from learning to cell growth and cancer.
“What caught our attention,” Dr. Gibbings states, “was the fact that when autophagy was inhibited the levels of microRNA decreased as well. It has been known for over ten years that microRNA levels decreased in almost every cancer tested and this contributes to cancer growth and spread. We believe that what we've discovered is a missing link that connects defects in autophagy and microRNA in cancer. It's a new link between two things we thought were independent phenomena in cancer cells.”
Dr. Gibbings thinks that this information may help drug companies develop better drugs for treating cancer.
While Dr. Gibbings and his team did not examine other diseases where autophagy is known to be problematic, they do believe it suggests there may be microRNA complications in those diseases as well.
“It opens up a new aspect for researchers to look into other diseases such as Alzheimer's, Parkinson's and Huntington's, where we know autophagy is defective. Our work suggests that the microRNA pathway will not be working as a consequence and this may very well be an important contributor to the pathology that brings people to the hospital with these diseases” Dr. Gibbings said.
Dr. Gibbings is excited to be starting his own research group at the University of Ottawa and believes that with what we are learning now, there is much left to discover about how the misregulation of RNA affects many diseases.
“Mutations in many genes controlling RNA result in diseases – it's our job to discover how, to find a solution,” he said.