Joel Watts

Perhaps the most important take home message from her work is that there is intrinsic structural variability between individual preparations of α-synuclein PFFs generated under identical conditions, which needs to be accounted for when designing and interpreting experiments.

One of Raphie's most interesting findings was that α-synuclein PFFs that mimic the seeding behavior of Parkinson's disease brain extract can be generated in vitro, but we only obtained the specific "PD-like" PFF polymorph once from 35 independent PFF preparations.

Online now in Neuron, the final published version of @xsakuraphie's PhD work on α-synuclein strain generation: Stochastic misfolding drives the emergence of distinct α-synuclein strains: Neuron cell.com/neuron/fulltex…

Genki's results support a model in which P4HB helps to stabilizes PrPC levels but also directly enhances the conversion of PrPC into PrPSc. Although much work remains to be done, targeting P4HB may constitute a new strategy for modulating prion replication.

I'm pleased to announce that our latest prion-related work is now available as a preprint: biorxiv.org/content/10.648… Dr. Genki Amano looked at whether P4HB, a protein disufide isomerase often identified in PrPC interactome screens, affects PrPC biosynthesis and prion replication.

The Protein Disulfide Isomerase P4HB/PDIA1 Modulates PrPC Levels and Prion Replication biorxiv.org/content/10.648… #biorxiv_neursci

A huge congratulations to Dr. Raphaella So (@xsakuraphie) on a wildly successful PhD defense today. Also, a big thanks to @lvolpic for serving as the external examiner.

Mount Pilatus in Lucerne, Switzerland. Amazing scenery and a fun luge-like ride down the hill.

Congratulations to all involved in this study (including @speedyerica), and a special thanks to Benedikt Frieg and José Camino for performing the cryo-EM experiments.

Furthermore, our work reveals that stochastic misfolding results in considerable prep-to-prep variability among PFFs, which can influence downstream phenotypes. Thus, the inherent variability of α-synuclein PFFs needs to be accounted for when designing/interpreting experiments.

It is my great pleasure to share our most recent work on α-synuclein strains: biorxiv.org/content/10.110…. This study was led by @xsakuraphie and represents an amazing collaboration with Gunnar Schröder's lab.

Lab field trip! It’s rare to have so many lab members at a conference together (since we usually travel in packs of 2-3, max) Thanks TRIDENT for having us :) Excited to be learning here in the beautiful town of London, ON @JoelWattsLab @SurabhiMehra5

@SurabhiMehra5 presenting her work on bank vole PrP knock-in mice at the @CJDFoundation Mechanisms of Neurodegeneration meeting.

Today is #CJDAwarenessDay. #Prions cause devastating neurological diseases such as CJD in humans. No cures are available, but promising research recently presented at the #Prion2024 conference. More about prion diseases and support here: cjdfoundation.org

Today is #CJDAwarenessDay. Check out this lovely collaborative video from the CJD International Support Alliance: cjdisa.com/video-globally… Help us spread the word to raise awareness and hope. #cjdawareness #priondiseaseawareness

A big thanks to everyone that contributed to this collaborative project. The bank vole PrP knock-in mice should be a useful resource for the field, and we're more than happy to share them with interested labs.

This suggests (perhaps not surprisingly) that the unusual properties of bank vole PrP are likely rooted in its intrinsic thermodynamic properties rather than its interaction with other proteins.

Our latest preprint is now online. Led by @NeuroHamza with contributions from @SurabhiMehra5, @speedyerica and others, we investigated the interactome of bank vole PrP (M109 isoform) using knock-in mice generated in collaboration with Walker Jackson. biorxiv.org/content/10.110…