2025 Hallett Memorial Scholarship - Mahdi Lavasani

Mahdi Lavasani received his BSc in Applied Chemistry and MSc in Organic Chemistry from Azad University of Tehran, followed by a second MSc in Industrial Chemistry from the University of Milan. He joined the University of Guelph in 2022 to pursue a PhD in Biophysics, focusing on the molecular underpinnings of Parkinson’s Disease (PD) through the study of alpha-synuclein (α-syn), a neuronal protein implicated in both physiological function and neurodegeneration. Throughout his studies, Mahdi has demonstrated originality and technical excellence, and a strong potential as a researcher.

Alpha-synuclein exists in a balance between its soluble monomeric form and membranebound states, with the latter prone to forming pathogenic aggregates. Emerging research suggests that α-syn may also interfere with autophagy, impairing the cell’s ability to clear damaged proteins and further promoting aggregation.

Mahdi’s thesis aims to elucidate the molecular interactions among α-syn, cellular membranes, and the autophagy-related protein LC3B. He has developed advanced solidstate Nuclear Magnetic Resonance (NMR) methods to probe the conformational states of membrane-bound α-syn, demonstrated that a reduction in membrane charge alters both protein mobility and membrane-binding affinity, and identified new exposed potential interaction sites. Complementing these findings with Thioflavin T assays, he has shown that membrane charge significantly influences the kinetics of α-syn aggregation. Mahdi has further used solution NMR to map three key regions that mediate α-syn’s interaction with LC3B, and is currently employing targeted mutagenesis to assess their individual contributions to complex stability.

The results he has obtained so far lay the foundation for addressing the final and central objective of his thesis: determining how membrane interactions modulate α-syn’s ability to engage with LC3B. Mahdi’s work offers valuable molecular insight into how α-syn may impair autophagy through its interactions with both membranes and autophagy machinery, thereby advancing our understanding of Parkinson’s Disease.