jasonsynaptic - Network

On the cancer side, we are working on implanting tumors with that express PNMA2 to try and recapitulate the paraneoplastic neurological...

On the cancer side, we are working on implanting tumors with that express PNMA2 to try and recapitulate the paraneoplastic neurological syndrome from antibodies to behavior deficits. Also want to know if other PNMA proteins have similar biology and figure out their functions in the brain! We welcome comments and feedback. This was 90% the work of Junjie, an amazing student in the lab! #neuroscience #autoimmune #capsids #cancer 6/6

We then got our hands on some rare patient CSF samples associated with paraneoplastic disorders that have PNMA2 antibodies. These patient...

We then got our hands on some rare patient CSF samples associated with paraneoplastic disorders that have PNMA2 antibodies. These patient antibodies also preferred to bind human PNMA2 capsid "spikes"! we have solved why these genes are implicated in paraneoplastic disorders! Lots of Qs remain: what the hell are these capsids doing in the brain? Why no membrane? Do antibodies cause neurological deficits because they interfere with normal signaling? /5

However, it seems that PNMA2 is released as non-enveloped "naked" capsids...WTF?! This is cray cray but further explains the...

However, it seems that PNMA2 is released as non-enveloped "naked" capsids...WTF?! This is cray cray but further explains the connection withan autoimmune response. To directly test this, Junjie and Matt injected purified PNMA2 capsids into mice and assessed autoantibody production. We also designed capsid assembly mutants based on the structure and found robust antibody production only with PNMA2 capsids. These autoantibodies preferred binding to the external "spike". /4

It's highly and almost exclusively expressed in neurons in the brain. But..why do these genes have such a weird name? Turns out that...

It's highly and almost exclusively expressed in neurons in the brain. But..why do these genes have such a weird name? Turns out that PNMA genes are associated with autoimmune diseases that have neurological symptoms most likely caused by certain kinds of cancers. But it had been a mystery why these proteins were immunogenic. So we obviously thought...ha, CAPSIDS. Junjie made a weird observation..we had previously shown that Arc is released from cells with a membrane in extracellular vesicles. /3

Junjie started purifying these proteins and found that a number of them could form virus-like capsids! The prettiest one was PNMA2 (check...

Junjie started purifying these proteins and found that a number of them could form virus-like capsids! The prettiest one was PNMA2 (check them out 😍). So we set out to characterize the cell biology and came together with our dream team Cedric Feschotte and John Briggs. Simon Erlendsson resolved the atomic structure using cryo-EM (again 😍). These capsids are small T=1. Manu's phylogenetic analysis showed that PNMA2 evolved from another Ty3 retrotransposon in mammals. /2

New lab preprint 🎇! 🧵about Junjie's exciting work on another retrotransposon derived Gag-like gene that has ALSO retained the...

New lab preprint 🎇! 🧵about Junjie's exciting work on another retrotransposon derived Gag-like gene that has ALSO retained the ability to make beautiful virus-like capsids! 5 years ago we showed that Arc forms endogenous capsids but is Arc unique? Turns out there are probably over a dozen genes in mammals that have similar evolutionary histories. One family of genes is expressed in brains but are poorly characterized - the paraneoplastic Ma antigen (PNMA) genes. https://www.biorxiv.org/content/10.1101/2023.02.09.527862v1 /1

Honored to receive a Brain Research Foundation Scientific Innovations award! Stay tuned for a preprint that forms the basis of this project....

Honored to receive a Brain Research Foundation Scientific Innovations award! Stay tuned for a preprint that forms the basis of this project. https://uofuhealth.utah.edu/neurobiology/news/2023/01/innovative-neuroscientist-u-of-u-health-recognized-risky-rewarding-brain

5 years ago, we published my favorite (so far) science of my career @cellcellpress! It has, and still is, leading us into new and unknown...

5 years ago, we published my favorite (so far) science of my career @cellcellpress! It has, and still is, leading us into new and unknown territory! Excited to put out some follow up work soon that sheds some light on the function of Arc intercellular signaling...AND data on other genes that have retained similar virus-like biology, with implications for cancer and neurological diseases.

#neuroscience #cellbiology #science
https://www.sciencedirect.com/science/article/pii/S0092867417315040

I didn't get out and do nearly as much #photography this year as I would have liked! Am definitely hoping to change this in 2023....

I didn't get out and do nearly as much #photography this year as I would have liked! Am definitely hoping to change this in 2023.

Here's one of my fav shots from this year...Lofoten Islands, #norway

Ugh...Twitter had it's ups and downs..but it has become so useful for networking for scientists, let alone #EDI discussions that have...

Ugh...Twitter had it's ups and downs..but it has become so useful for networking for scientists, let alone #EDI discussions that have been super informative for me! Looks writing is on the wall though...can Mastodon or Post fill the void? #science #academia #neuroscience

I honestly enjoyed twitter for the range of folks I could follow and interact with...not so sure this is doable on here? Landscape...

I honestly enjoyed twitter for the range of folks I could follow and interact with...not so sure this is doable on here?

Landscape photography became a hobby after moving to Utah...and it's kept me sane. Here's one from the Utah desert.

Whelp...we may be all on here come next week! #twitterMigration #academia

Whelp...we may be all on here come next week! #twitterMigration #academia

No idea how this thing works...but here's my first post! Will see how the dumpster fire pans out on twitter. #neuroscience #scicomm...

No idea how this thing works...but here's my first post! Will see how the dumpster fire pans out on twitter.

#neuroscience #scicomm #academia