a man in a suit and tie is smiling and says you 're gonna love it ALT: a man in a suit and tie is smiling and says you 're gonna love it

#USASP_2026 Come see some cool research using novel tools to measure neuronal activity by the Szablowski Lab at Rice @jerzyszablowski.bsky.social

Because my lab was located at a @nprcnews.bsky.social we had resources to move fast and within months Jerzy and Sin had redesigned a version of the RMA protein for IG1 Fc receptor in primates they called, NHP-RMAs. We injected the protein into the brain and O.M.G it worked inspiring this tweet.

We will be making a marmoset version soon fwiw, but the NHP version worked in mice, so I wouldn't be surprised if the macaque version worked in marmoset.

i think i have an ipod shuffle somewhere

Monitoring gene expression in the brain with a simple blood test?

In collaboration with @jerzyszablowski.bsky.social & his lab we figured out how to do it nonhuman primates using noninvasive neuroengineering of synthetic serum markers.

nam11.safelinks.protection.outlook.com?url=https%3A...

How can serum marker tests be made more sensitive? The lab of @jerzyszablowski.bsky.social shows that editing markers in vivo to reduce their half-life can provide more sensitive measurement of gene expression dynamics. Read more:

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

A humanized NOVA1 splicing factor alters mouse vocal communications - Nature Communications The neuron-specific RNA binding protein NOVA1 has a single amino acid substitution unique to modern humans. Here, the authors characterize the evolutional specificity and the function of the substitut...

Neat

www.nature.com/articles/s41...

I wonder if it's a statistically significant uptick.

Addgene now has the NHP-RMAs available - the synthetic serum markers for measuring transgene and Cre-dependent expression, from the preprint (www.biorxiv.org/content/10.1...) with @vincentcostaphd.bsky.social lab.

plasmids for order:
www.addgene.org/browse/artic...

It does take a lot. The hope is that all the companies doing BBB permeable AAVs like Apertura, Capsida, Sangamo, Voyager etc. will find something that works 10-100-fold more efficiently.

Ultrasound BBB opening in large animals (or humans) is doable but somewhat complex. I do think the prices and complexity will go down over time for both gene delivery and BBB opening.

Acoustically targeted measurement of transgene expression in the brain - PubMed Gene expression is a critical component of brain physiology, but monitoring this expression in the living brain represents a major challenge. Here, we introduce a new paradigm called recovery of marke...

Doing whole brain BBB-permeable gene delivery + with FUS release of synthetic markers could allow to study multiple sites without surgery and monitoring intracellular gene expression. e.g.
pubmed.ncbi.nlm.nih.gov/39110811/

That would be neat. Hong Chen at WUSTL has done some pioneering work in using FUS to release native proteins from the brain into the blood. There's non zero chance that native proteins carry sufficient information. If not, then the synthetic markers probably will, but would need gene delivery.

What do you want to study? I am always curious about what are the experimental hurdles people have. I am wondering if it site-specific liquid biopsy would be useful for you. It's much more technically complicated but can study different regions on different days.

There are some hurdles for human translation eg need for exogenous gene delivery. There are also ways to mitigate them. If our bright focus grant works out it should make translation realistic. There will be more work on optimization in nhps like higher signal, longer duration, recording c-fos etc

Author list:

How can you know if gene delivery in a primate worked Typically through expensive scans or histology. With
@vincentcostaphd.bsky.social
and co-authors we made synthetic markers that monitor gene delivery and Cre-dependent expression with a blood test:
www.biorxiv.org/content/10.1...

Thanks Mark. I think we were surprised it worked so robustly. Still lots of work to do, in mice we could do orders of magnitude signal and track c-fos, arc etc. Next paper, if we can get the funding. This was done on a shoestring.

Site-Specific Noninvasive Delivery of Retrograde Viral Vectors to the Brain Neuronal activity underlies the brain function. Different behaviors, physiological processes, and disorders depend on which neurons are active at a given moment. Treating brain disorders without side ...

www.biorxiv.org/content/10.1...

Lead author: Manwal Harb, who also contributed to engineering AAV.FUS, vector optimized for noninvasive site specific gene delivery to the brain.
www.nature.com/articles/s41...

Work supported by The G. Harold & Leila Y. Mathers Charitable Foundation

What is the next frontier in brain therapy? Small molecules act everywhere; our work targets brain regions with mm precision. Next frontier? Targeting microscale - neuronal connections, ensembles. Here, we test AAV9.retro for noninvasive transduction of neuronal projections. preprint comments

Jordan, we missed you at the ACS! I hope you're doing well

The MIT McGovern Institute’s story celebrating the 10th birthday of expansion microscopy (ExM). One highlight: ExM is not only easy to do, it’s easy to modify - so lots of people are altering and applying ExM for custom purposes, leading to unexpected innovations: mcgovern.mit.edu/2025/03/03/t...

Posting this image of neurons transfected to secrete proteins that @jerzyszablowski.bsky.social bioengineered to enable noninvasive monitoring of neuronal integrity in NHPs for #fluorescentfriday.

This technology will eventually lead to improved treatments for neurodegenerative disorders.

We are starting our
@ARIA_research
Precision Neurotechnologies project and have two non-postdoc positions in neuroscience and bioengineering. This funding is independent of US government.

Jobs:
emdz.fa.us2.oraclecloud.com/hcmUI/Candid...

More info:
tinyurl.com/hwsnrwpe

-- please RT --

Did you all start sciencing harder recently, or something?

i think it would be for more surprising if the mixture wasn't racemic...

They are about a half of what we get paid here, but money isn't everything.

A quick reminder: For every $1 of research funding, NIH generated $2.46 in economic activity. This includes funding jobs in all 50 states. This isn't a red/blue thing: 8.9 jobs per $1M in CA & 12 jobs per $1M in GA. #AcademicSky #PhDSky #MedSky #HealthSky #healthequity #SciComm
bit.ly/40NkIc0

I am looking forward to working with @LignaniLab_UCL and others on this @ARIA_research neurotechnologies grant. A ~$2.5m contribution to our lab's work that will help us make next generation noninvasive brain therapies for specific brain circuits.

news.rice.edu/news/2025/ri...

this book brings back good memories!