Dane Marijan
Hi, I'm a molecular cell biologist
passionate about education and science communication
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Research
To perform their duties proteins need to be of a certain shape, but sometimes they can get misshapen and uncontrollably clump together, an event often seen in disease. However, cells seem to have developed a way to precisely control the clumping of some proteins to survive harsh conditions like high temperature. My PhD research focused on figuring out what mechanism decides whether or not proteins will aggregate in this protective way in harmful environments.
Curriculum Vitae
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Research
Here are the main projects I worked on during my PhD. For a full list of publications click here.
Protein thermal sensing regulates physiological amyloid aggregation
To survive, cells must respond to changing environmental conditions. One way that eukaryotic cells react to harsh stimuli is by forming physiological, RNA-seeded subnuclear condensates, termed amyloid bodies (A-bodies). The molecular constituents of A-bodies induced by different stressors vary significantly, suggesting this pathway can tailor the cellular response by selectively aggregating a subset of proteins under a given condition. Here, we identify critical structural elements that regulate heat shock-specific amyloid aggregation. Our data demonstrates that manipulating structural pockets in constituent proteins can either induce or restrict their A-body targeting at elevated temperatures. We propose a model where selective aggregation within A-bodies is mediated by the thermal stability of a protein, with temperature-sensitive structural regions acting as an intrinsic form of post-translational regulation. This system would provide cells with a rapid and stress-specific response mechanism, to tightly control physiological amyloid aggregation or other cellular stress response pathways.See full publication here.
Stress‐specific aggregation of proteins in amyloid bodies
Physiological amyloid aggregation occurs within the nuclei of stress-treated cells. These structures, termed Amyloid bodies (A-bodies), assemble through the rapid accumulation of proteins into dense membrane-less organelles, which possess the same biophysical properties as plaques observed in many amyloid-based diseases. Here, we demonstrate that A-body proteomes vary significantly between stimuli. We propose that different environmental conditions induce the formation of A-body subtypes containing distinct protein residents, and that selective immobilization of proteins may have evolved as a finely tuned mechanism for surviving divergent stressors.See full publication here.
Stress-mediated aggregation of disease-associated proteins in amyloid bodies
The formation of protein aggregates is a hallmark of many neurodegenerative diseases and systemic amyloidoses. These disorders are associated with the fibrillation of a variety of proteins/peptides, ultimately leading to cell toxicity and tissue damage. Understanding how amyloid aggregation occurs and developing compounds that impair this process is a major challenge in the health science community. Here, we demonstrate that pathogenic proteins associated with Alzheimer’s disease, diabetes, AL/AA amyloidosis, and ALS can aggregate within stress-inducible physiological amyloid-based structures, termed amyloid bodies (A-bodies). Using a limited collection of small molecule inhibitors, we found that diclofenac could repress amyloid aggregation of the beta-amyloid (1–42) in a cellular setting, despite having no effect in the classic Thioflavin T (ThT) in vitro fibrillation assay. Mapping the mechanism of this repression indicated that dysregulation of cyclooxygenases and the prostaglandin synthesis pathway was potentially responsible for this effect. This work suggests that the A-body machinery may be linked to a subset of pathological amyloidoses, and highlights the utility of this model system in finding new small molecules that could treat these debilitating diseases.See full publication here.
Teaching
Teaching Assistant in undergraduate courses at Simon Fraser University• Cellular biology and biochemistry (MBB 231 - online) - Summer semester 2020
• Cellular biology and biochemistry (MBB 231) - Fall semester 2019
• Cellular biology and biochemistry (MBB 231) - Spring semester 2019
• Molecular biology and biochemistry (MBB 222) - Spring semester 2018
Curriculum Vitae
Education• PhD in Molecular Biology and Biochemistry (2017-2023)
Audas Lab, Faculty of Science, Simon Fraser University, CanadaThesis: A protein thermal sensing mechanism for newly characterized stress-specific amyloid body recruitment. link• BSc in Biology, module Molecular Biology and Physiology (2013-2017)
Faculty of Biology, University of Belgrade, SerbiaPublicationsMarijan D., Momchilova E.A., Burns D., Chandhok S., Zapf R., Wille H., Potoyan D., and Audas T.E. (2024), Protein Thermal Sensing Regulates Physiological Amyloid Aggregation. Nature Communications doi.org/10.1038/s41467-024-45536-0Chandhok S., Pereira L., Momchilova E.A., Marijan D., Zapf R., Lacroix E., Kaur A., Keymanesh S., Krieger C., Audas T.E. (2023), Stress-Mediated Aggregation of Disease-Associated Proteins in Amyloid Bodies. Scientific Reports doi.org/10.1038/s41598-023-41712-2Lacroix E., Pereira L., Yoo B., Coyle K.M., Chandhok S., Zapf R., Marijan D., Morin R.D., Vlachos S., Harden N., and Audas T.E. (2021), Evolutionary Conservation of Systemic and Reversible Amyloid Aggregation. Journal of Cell Science doi.org/10.1242/jcs.258907Theodoridis P.R., Bokros M., Marijan D., Balukoff N.C., Wang D., Kirk C.C., Budine T.D., Goldsmith H.D., Wang M., Audas T.E., and Lee S. (2021), Local Translation in Nuclear Condensate Amyloid-Bodies. PNAS USA doi.org/10.1073/pnas.2014457118Marijan D., Tse R., Elliott K., Chandhok S., Luo M., Lacroix E., and Audas T.E. (2019), Stress‐Specific Aggregation of Proteins in the Amyloid Bodies. FEBS Letters (Editor's Choice) doi.org/10.1002/1873-3468.13597Presentations (selection)Keystone Symposium: Protein-RNA Interactions & Biomolecular Condensates, Poster: "Protein thermal sensing regulates physiological RNA-seeded amyloid aggregation" (2023)Proteostasis Researchers in Canada (PRinCE) virtual seminar series, 1st place Presentation: "Protein Thermal Sensing Regulates Physiological Amyloid Aggregation" (2023)Ribowest Conference, 2nd place Presentation: "Intrinsic Protein Structural Properties Regulate Physiological Amyloid Aggregation" (2022)Frontiers in Biophysics Conference, 2nd place Presentation: "Intrinsic Protein Structural Properties Regulate Physiological Amyloid Aggregation" (2022)Autophagy and Other Cell Stress Networks Symposium, 1st place Poster: “Defining the Mechanism of Stress-Specific Amyloid Body Formation” (2019)Ribowest Conference, 1st place Poster (student selection): “Aggregation discrimination: two 90% identical RNA helicases are differentially targeted by a novel ncRNA mediated amyloid aggregation pathway” (2018)Awards and ScholarshipsSimon Fraser University, Canada
• MBB Dr. Bruce Brandhorst Best PhD Thesis Prize (2023)
• Graduate Fellowship (Awarded 6 times 2017-2023)
• Weyerhauser Graduate Scholarship (Awarded 3 times 2020-2023)
• David Baillie Graduate Fellowship (Awarded 2 times 2021-2023)
• President’s PhD Scholarship (2021)Teaching ExperienceWorkshops and Programs (SFU Centre for Educational Excellence)
• Completed Certificate Program in University Teaching and Learning (2022)
• Completed Instructional Skills Workshop (2019)Teaching Assistantships (Simon Fraser University)
• Cellular biology and biochemistry – undergraduate course (3 times, 2019-2020)
• Molecular biology and biochemistry – undergraduate course (2018)