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SUMMARY:A Deep Dive into Biomolecular Condensates using Vibrational Raman 
 and Single-Molecule FRET - Speaker to be confirmed
DTSTART:20230609T130000Z
DTEND:20230609T140000Z
UID:TALK202168@talks.cam.ac.uk
CONTACT:Margarida Rodrigues
DESCRIPTION:Formation of biomolecular condensates via liquid-liquid phase 
 separation of intrinsically disordered proteins/regions (IDPs/IDRs) and nu
 cleic acids into membraneless organelles is involved in critical cellular 
 functions and debilitating human diseases. We discovered that the prion pr
 otein (PrP) (well-known for its association with mad cow disease and Creut
 zfeldt-Jakob disease) can undergo phase separation via weak\, multivalent\
 , transient intermolecular interactions between the N-terminal IDR that re
 sembles a yeast prion-like domain. An intriguing disease-associated amber 
 stop codon mutation (Y145Stop) of PrP yields a C-terminally truncated intr
 insically disordered fragment. We demonstrated that Y145Stop spontaneously
  phase-separates into highly dynamic liquid droplets under physiological c
 onditions. Upon aging\, these highly dynamic liquid droplets undergo a liq
 uid-to-solid phase transition into highly ordered\, beta-rich\, amyloid-li
 ke aggregates that exhibit a characteristic autocatalytic self-templating 
 behavior. The propensity for the aberrant phase transition is much lower f
 or the full-length PrP indicating an evolutionarily conserved role of the 
 folded C-terminal domain. Our recent results also showed intriguing spatio
 temporal modulations in complex coacervation of PrP with other neuronal ID
 Ps (alpha-synuclein and tau) into heterotypic\, multicomponent\, multiphas
 ic\, 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 ex
 quisite molecular details of biomolecular condensates and dissect the cruc
 ial molecular events of phase separation. 
LOCATION:Unilever  Lecture Theatre\,  Department of Chemistry
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