Raphaella So, PhD

My PhD work is now *published* at Neuron!
1) Multiple structures of #synuclein aggregates form under the same uniform condition
2) You can't predict which structure you'll get
3) Different structures cause different disease outcomes in mice
#NeuroSky #Parkinsons 🧪
www.cell.com/neuron/fullt...

Coolest thing I’ve read this week! 😎🧪

Check this 🧵 for some amazing implantation #science.

The neural control & computation lab is recruiting!

If you're interested in using large-scale neural population recordings to study how the brain learns to produce complex and flexible behaviours, please get in touch.

www.ncclab.ca

Hamster with paws on the ledge of a bin

Hamster with almond in his mouth

Hamster foraging on flax

Hamster with an expressionless face munching on dried sweet potatoes

Peanuts the hammy decided to grace us with his presence at lunch

With this, I would like to thank the CIHR, Croucher Foundation, Parkinson Canada @parkinsoncanada.bsky.social , Peterborough KM Hunter Charitable Foundation, and Ontario Graduate Scholarship for funding our research.
If you've read this far, thank you for reading and I'm happy to take any questions!

Our findings also imply that even when experimental conditions are all controlled for, strain variability inherently exists in de novo α-syn aggregates generated in vitro or derived from the M83 mouse model. This needs to be taken into account when we design/interpret α-syn studies in the future.

Our observations that distinct strains come from the same experimental setup (for recombinant α-syn) and from the same genotype of mice (for naturally occurring aggregates) suggest that random protein misfolding is a major driver of α-syn strains and disease heterogeneity in the synucleinopathies.

As homozygous M83 mice spontaneously develop synucleinopathies, we also examined the naturally occurring strain diversity of their α-syn aggregates, and found that they could form 1 of 3 types of aggregates, which propagated as 3 different strains.

i.e. Multiple strains arise naturally, randomly.

Using biochemical assays and cryo-EM, we found that in the same condition, wild-type and A53T-mutant α-syn can form multiple α-syn structures. These structures propagated as distinct strains in our mouse model (M83 mice, which overexpresses the A53T-mutant human α-syn and develops a fatal disease)

With the link between different strains and different diseases established, we then wondered why different strains form. Specifically, we asked whether different strains can form when aggregates are made in identical conditions -- because if so, the reason may be random misfolding.

Spoiler: yes.

α-Synuclein strains target distinct brain regions and cell types - Nature Neuroscience Lau et al. find that α-synuclein strains initiate distinct diseases when injected into mice, which provides a potential molecular explanation for the clinical and pathological differences between Park...

That shape/structure is what we call a "conformational strain." Previously, we published that making α-syn aggregates in the test tube in the presence vs. absence of salt creates two different strains that cause drastically different neurological diseases in mice www.nature.com/articles/s41...

α-Synuclein Conformational Strains as Drivers of Phenotypic Heterogeneity in Neurodegenerative Diseases The synucleinopathies, which include Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, are a class of human neurodegenerati…

Weirdly enough, a vast majority of Parkinson's and DLB patients, and all MSA patients, express the same wild-type version of α-syn. So why do different patients get different diseases? The secret may lie in the shape in which multiple α-syn proteins are attached www.sciencedirect.com/science/arti...

Alpha-synuclein protein aggregates are a common pathological hallmark of multiple neurodegenerative diseases, including Parkinson's, Multiple System Atrophy, and Dementia with Lewy Bodies. α-Syn gene duplications, triplications, and mutations are known causes for familial Parkinson's and DLB.

My PhD work at the Joel Watts lab is now online! It is an ultrastructural, biochemical, and neuropathological investigation into different structures of α- #synuclein (α-syn) aggregates, done in collaboration with Gunnar Schröder's lab.
#NeuroSky #Parkinsons 🧪
www.biorxiv.org/content/10.1...

Stochastic Misfolding Drives the Emergence of Distinct α-Synuclein Strains https://www.biorxiv.org/content/10.1101/2025.06.03.657690v1

I am constitutionally incapable of encountering this video without watching the whole thing.

With all noise out of DC, it's easy to forget that Greenland's ice sheet is fragile. It's melted away before raising sea level 6 m (20+ ft). Free read - fossil evidence from under the ice.
❄️💙📚
#scicomm
#climate
#UVMresearch
#science
🧪 🌎 ⚒️
#ClimateHealth
#ClimateAction

www.pnas.org/doi/10.1073/...

Hamster posing with flax

Hamster’s face squished trying to get to his flax

Hamster looks derpy trying to eat his flax

Hamster bends himself to seemingly impossible lengths for flax

My pet hamster Peanuts does derpy things when food is in sight.

FDA cancels vaccine advisory meeting for choosing flu strains for next season's shots It comes as RFK Jr., a vaccine skeptic who now leads the Department of Health and Human Services, makes moves that could affect vaccination uptake and policy.

If they don’t reverse course, we may not have lifesaving flu shots next year. Because actual inefficiency and antivaccine people have taken over our national healthcare agencies. 🧪

www.cnbc.com/amp/2025/02/...

Hold on while I copypasta into my CV....but also read up in thread for important tool on how to convey the importance of your work 🧪

New late night writing record: my upcoming paper's introduction section, 3am.
(last time was my committee meeting report, 1 sth am, >6 years ago)

I just wanted to get to the part where I yell about a-syn strains being strains because they fit the definition of strains. to spite the strain deniers.

Sir Snacks-a-lot is always working 🍎

Finally! The Hydroxychloroquine study by Gautret et al. has been retracted. I wrote a critical post about it in March 2020, days after it came out.

scienceintegritydigest.com/2020/03/24/t...

Microglial APOE3 Christchurch protects neurons from Tau pathology in a human iPSC-based model of Alzheimer’s disease

www.cell.com/cell-reports...

a cartoon drawing of a man standing next to another man Alt: a cartoon drawing of a man dancing and swinging a lanyard around his neck

I’ve got it, the next big innovation in conference technology!

…are you ready for this?

Printing the name on BOTH SIDES OF THE BADGE

🧪

The evolution of my font preferences through graduate school:
Times New Roman
—> Arial
—> Helvetica (currently here)

People | TRIDENT Website

My labmates just warned me that our "for funsies" photo made it to the joint-universities research project website.
As a representative "people" shot.

I'm getting a good laugh over this.

www.tridentpreclinicaltrials.org/people

trying to relate to people in the comments

Roborovski hamster with his paws on a flat wooden platform in front

Roborovski hamster eating a snack in a sand bath, facing the camera

Roborovski hamster crawling out of his sand bath

Roborovski hamster booping the camera

Some eye bleach for y’all:
My hamster Peanuts