A Deep Dive into Biomolecular Condensates using Vibrational Raman and Single-Molecule FRET

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• Speaker to be confirmed
• Friday 09 June 2023, 14:00-15:00
• Unilever Lecture Theatre, Department of Chemistry.

If you have a question about this talk, please contact Margarida Rodrigues.

Formation of biomolecular condensates via liquid-liquid phase separation of intrinsically disordered proteins/regions (IDPs/IDRs) and nucleic acids into membraneless organelles is involved in critical cellular functions and debilitating human diseases. We discovered that the prion protein (PrP) (well-known for its association with mad cow disease and Creutzfeldt-Jakob disease) can undergo phase separation via weak, multivalent, transient intermolecular interactions between the N-terminal IDR that resembles a yeast prion-like domain. An intriguing disease-associated amber stop codon mutation (Y145Stop) of PrP yields a C-terminally truncated intrinsically disordered fragment. We demonstrated that Y145 Stop spontaneously phase-separates into highly dynamic liquid droplets under physiological conditions. Upon aging, these highly dynamic liquid droplets undergo a liquid-to-solid phase transition into highly ordered, beta-rich, amyloid-like aggregates that exhibit a characteristic autocatalytic self-templating behavior. The propensity for the aberrant phase transition is much lower for the full-length PrP indicating an evolutionarily conserved role of the folded C-terminal domain. Our recent results also showed intriguing spatiotemporal modulations in complex coacervation of PrP with other neuronal IDPs (alpha-synuclein and tau) into heterotypic, multicomponent, multiphasic, multilayered condensates in the presence of RNA . If time permits, I will also discuss our surface-enhanced Raman scattering (SERS) and single-molecule FRET (Förster resonance energy transfer) studies that capture exquisite molecular details of biomolecular condensates and dissect the crucial molecular events of phase separation.

This talk is part of the Centre for Physical Biology talks series.

This talk is included in these lists:

• Centre for Physical Biology talks
• Unilever Lecture Theatre, Department of Chemistry

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