I was a lucky participant in the inaugural HKLF in 2023. I had the honor of presenting my research to Laureates from different fields during the poster session, then to Franz-Ulrich Hartl and Peter Greenberg during my flash talk. What was exceptionally memorable was that Dr. Hartl stayed behind to chat with me about my research process and the rationale behind certain key experiments of my project. I gained so much inspiration from our interaction and from his interest in my work. In addition to meeting and learning from the Laureates, I also enjoyed networking with the fellow Young Scientists. Spending a week together attending lectures and touring Hong Kong helped us grow close, and I am grateful for the meaningful friendships and collaborative relationships I have made. In fact, a fellow Young Scientist recently invited me to give a research seminar to his students – a promise I look forward to fulfilling the next time I am in Hong Kong. HKLF 2023 was truly phenomenal and I would love to be invited back to HKLF 2025 to catch up with my old conference buddies, make new friends, and chat about science with more Shaw Laureates.

University of Toronto

The “synucleinopathies” is an umbrella term encompassing neurodegenerative diseases that have α-synuclein protein aggregates as their pathological hallmark, such as Parkinson’s. The conformational strain hypothesis, or the theory that the same α-synuclein protein monomer can aggregate into different structures, provides a potential explanation for the clinical and pathological differences among the human synucleinopathies. However, how different strains are formed remains unknown. Here, we examined α-synuclein aggregates made within a consistent molecular environment. Using recombinant A53T mutant human α-synuclein, wild type human α-synuclein, and transgenic mice that spontaneously develop α-synuclein aggregates (homozygous M83 mice), we observed that multiple conformers of α-synuclein aggregates were capable of forming under identical experimental conditions in vitro and in vivo. Upon inoculation into mice, these α-synuclein aggregates maintained their different biochemical properties and caused distinct disease progression rates and α-synuclein deposition patterns in the brain. We identified 2 distinct A53T mutant α-synuclein strains, 3 distinct M83 strains, and at least 3 distinct wild type α-synuclein strains. As their formation conditions were identical, we concluded that the emergence of distinct strains was due to stochastic misfolding. Our work brings important implications to the design and interpretation of experiments using recombinant aggregates or M83 mice.