Cellular ability to react to stressors such as extreme temperatures, hypoxia, determines the sustainability of the entire organism. Tim Audas at Simon Fraser University has uncovered the mechanism by which proteins are reversibly folded and immobilized in amyloid bodies in response to stress. In a presentation he gave at the Keystone Symposium on “Cellular Stress Responses and Infectious Agents” in Santa Fe, Tim Audas describes this process of amyloidogenesis as a means of ensuring survival and homeostasis under adverse conditions. Amyloidogenesis, which is well-known in the context of neurological disorders such as Alzheimer’s and Parkinson’s disease, helps the cell to enter a state of protective dormancy by sequestering diverse proteins in sub-nuclear foci, termed A-bodies. To mimic physiological stress, Dr. Audas cultured cells at 1% oxygen in the HypOxystation, also exposing them to acidosis for additional stress. The HypOxystation’s closed workstation format ensures controlled oxygen, CO2, temperature and humidity conditions throughout the duration of culture and manipulation. Dr. Audas states that, “The workstation is critical because it allows us to manipulate the cells within a low oxygen environment and, unlike an incubator, maintains the O2 levels when cells are taken in and out, avoiding spikes of normoxia“.

 Dr. Audas was able to show that proteins are targeted to the A-bodies by a specific motif which interacts with ribosomal intergenic noncoding RNA (rIGSRNA). Thus, A-body formation effectively halts cell proliferation, helping cells to remain viable during periods of stress. He demonstrated that inhibition of rIGS28RNA-mediated A-body formation via shRNA abrogates that cellular dormancy in highly hypoxic tumor regions. The results obtained by the Audas lab provide important insight into both physiological and pathological amyloidogenesis and “will enhance our understanding of neurological diseases”.  Click here to view published paper.