Nathan Moerke

Rapamycin's Secrets

Never assume that you know all about what any drug molecule is doing in the body - where it's going, what it's binding to. A new example:

Used to see them all the time in Brookline close to Harvard Medical School, they sometimes could act aggressive around people.

CBER Roundtable on Cell and Gene Therapy The Roundtable will provide you with an opportunity to share your thoughts on advancing the field of cell and gene therapy.

🔊 TOMORROW, June 5: Join @fda.gov’s Cell and Gene Therapy Roundtable featuring ASGCT Board Members Terry Flotte, Paula Cannon, and more, on the panel! Watch on YouTube from 9 a.m. to noon (ET).

Do not miss out on this opportunity to hear from top regulatory leaders! www.fda.gov/vaccines-blo...

Vancouver council is debating a giant permanent sign that says "VANCOUVER", and staff say an issue is putting the sign in a place that won't interfere with film shoots.

In other words, a giant "VANCOUVER" sign could interfere with vancouver's lucrative business of pretending to be any other city

Allen’s hummingbird flying above an Anna’s hummingbird perched

Sheer luck to freeze this moment where both hummingbirds are both sharp in the same frame

I’ve had my share of photos with two or more birds in the same frame. Even a few lucky enough to have two different species interacting

This Allen’s and Anna’s hummingbird being territorial is a good one 📷🪶

The End of Disease

Thoughts on Demis Hassabis of Google DeepMind saying that AI could cure disease in general in ten years.

Bonus index to my longer posts on AI/computational drug discovery over nearly 20 years!

Odd that Booker doesn't show up in this poll, since in the Echelon poll just released he was in 2nd at 11%, seems like his stock has been rising after the marathon speech.

Harsh truths in drug discovery: we still have so much to learn about biology.

There is much work to be done before we cure every disease.

Great Cell article from James Fraser and Matt Murcko (yes, open access)

www.sciencedirect.com/science/arti...

A gray wolf clone with dire wolf DNA edits.

It's not a dire wolf. It's a gray wolf clone with 20 dire-wolf gene edits, and with some dire wolf traits. And here's my story! Gift link: www.nytimes.com/2025/04/07/s...

A cerebrospinal fluid synaptic protein biomarker for prediction of cognitive resilience versus decline in Alzheimer’s disease - Nature Medicine The ratio between the levels of two synaptic proteins in cerebrospinal fluid predicts future cognitive resilience versus decline among presymptomatic individuals and individuals with early Alzheimer’s...

Nice work to identify a new CSF biomarker for cognitive decline in AD via the ratio of two synaptic proteins - the team is also working on developing an equivalent plasma biomarker:

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

MIT engineers turn skin cells directly into neurons for cell therapy MIT researchers devised a process to convert a skin cell directly into a neuron, eliminating the need to generate induced pluripotent stem cells. Such neurons could be used to treat spinal cord injuri...

New streamlined method to directly convert mouse fibroblasts into functional motor neurons, with significantly improved efficiency:
news.mit.edu/2025/mit-eng...

The discovery of a pro-invasive mechanotransduction pathway driven by cell crowding suggests that an ion channel called TRPV4 may be a promising therapeutic target for inhibiting metastasis.
buff.ly/lNQRGux

Good question - I don't know anything about their data privacy policies, but you do have the option of running DeepSeek offline locally on your own machine (assuming it has enough horsepower).

Playing around with DeepSeek for literature review - so far seems good at summarizing individual articles but when asked to provide references relevant to a specific topic tends to hallucinate articles that don't actually exist.

Clinical Trial Readouts Are A-Comin'

Some clinical trial results to look forward to this year:

Nice examples of the use of brain organoids to study the relationship between HSV-1 infection and neurodegeneration:

www.alzforum.org/news/researc...

Confronting risks of mirror life Broad discussion is needed to chart a path forward.

Gearing up vs the potential of building "mirror life"
A looming danger of bioengineered reversed-chirality bacteria and microbes.
www.science.org/doi/10.1126/... @science.org

Perception of Temperature Even in the Absence of Actual Change is Sufficient to Drive Transgenerational Epigenetic Inheritance Can processes occurring in one individuals nervous system influence the physiology of the descendants? Here we explored the provocative hypothesis that parents sensation or perception of environmental...

Scared to share this after 10 freaking years of waiting, but here we go: We found that temperature *perception* can change the biology of the next generations, even when “it’s just in the parents' head”. Read how C. elegans neurons control epigenetic inheritance!
www.biorxiv.org/content/10.1...

Whole-brain spatial transcriptional analysis at cellular resolution Recent advances in RNA analysis have deepened our understanding of cellular states in biological tissues. However, a substantial gap remains in integrating RNA expression data with spatial context acr...

Kanatani et al. report the development of a brain tissue–clearing method called TRISCO, which enables three-dimensional in situ hybridization on the whole brain, allowing the visualization of specific mRNAs in the complete brain at cellular resolution

www.science.org/doi/10.1126/...

Gene therapy to treat chronic pain - Sangamo has received FDA clearance to start clinical trials for their zinc finger repressor targeting SCN9A:
investor.sangamo.com/news-release...

CNS Drug Development: Same As It Ever Was

Developing new drugs for central nervous system diseases like depression is extremely difficult - and the story of Sage Therapeutics illustrates that all too well:

Exploring the full bluesky firehose, in three dimensions: firehose3d.theo.io

I’m creating a drug development starter pack, reach out to join or suggest additions: go.bsky.app/B2pzQm2

Miner bee on dandelion

First post on Bluesky. Let's do some Macro photography and see how thos works 📸😊 #photography

Nice library of free public domain illustrations for figures and presentations from NIH:
bioart.niaid.nih.gov

Encoded Demonstrates Therapeutic Potential of a Vectorized miRNA-based Approach for Angelman Syndrome at the FAST Annual Global Science Summit New preclinical data for candidate ETX201 illustrate its potential as a first-in-class gene therapy for Angelman syndrome. Studies in non-human primates demonstrate safety, biodistribution, and target...

New preclinical data on a first-in-class gene therapy for Angelman syndrome:
encoded.com/press-releas...

AlphaFold (and its peers) are wonderful tools, but don't imagine that they can replace actual experimentally determined protein structures. The details:

A weirdly effective way to make better antibodies even ones that have already been optimized: