iiinova — where your digital self keeps evolving

Coleen Murphy @ctmurphy1.bsky.social · 01/08/2026

The joint Bargmann/Kenyon lab meeting is responsible for our kids

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Coleen Murphy @ctmurphy1.bsky.social · 25/05/2026

2025+2026 graduates Alden Weiner, Borja Ceballos Llera, and Dinora Rivas Rodriguez

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Coleen Murphy @ctmurphy1.bsky.social · 17/05/2026

Athena in her roast chicken pose

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Coleen Murphy @ctmurphy1.bsky.social · 22/02/2026

And here are some foxes who visit our yard

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Coleen Murphy @ctmurphy1.bsky.social · 15/01/2026

Summary: THIS AI REVIEWING TOOL IS DANGEROUS. If editors use AI tools to review, they may desk-reject papers just because the tool suggests many but pointless experiments, while missing fundamental flaws.

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Coleen Murphy @ctmurphy1.bsky.social · 15/01/2026

b. Our paper: the review tool missed the whole point of the paper (memory) and suggested about 3yrs worth of pointless experiments (all were on lifespan/healthspan, not at all the point of the paper).

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Coleen Murphy @ctmurphy1.bsky.social · 15/01/2026

a. JC-reviewed paper: our lab's JC review identified a fatal, fundamental flaw in the paper that rendered the whole study useles, as well as other more minor problems layered on top of that, but the review tool only identified the minor issues, and missed the major problem with the whole paper.

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Coleen Murphy @ctmurphy1.bsky.social · 15/01/2026

4. AI reviewing tools: This was most eye-opening to me. Submitted two bioRxiv papers we knew well - one we had a journal club on to review, the other from our lab - to the new open-access reviewing tool available through bioRxiv. Results were terrible in both cases:

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Coleen Murphy @ctmurphy1.bsky.social · 15/01/2026

3. AI and fraud: terrifyingly good facsimiles of Western blot data. Not sure how journals are going to deal with this.

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Coleen Murphy @ctmurphy1.bsky.social · 15/01/2026

2. What AI is not OK/very bad for: a. Writing - we are trying to teach students to write, so if they use AI, they are not learning the material and they are not learning how to write well.

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Coleen Murphy @ctmurphy1.bsky.social · 11/01/2026

Good to see people out protesting against ICE - and lots of support from drivers passing (the exceptions were notable and few)

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Coleen Murphy @ctmurphy1.bsky.social · 06/12/2025

This is a ridiculous place to sleep

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Coleen Murphy @ctmurphy1.bsky.social · 01/11/2025

The Princeton museum opening was (is) a blast! Best costumes: Frida Kahlo (several), Louvre heist crew

Woman in green next to painting of woman in green

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Coleen Murphy @ctmurphy1.bsky.social · 28/10/2025

Saw a nice moon through a telescope tonight

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Coleen Murphy @ctmurphy1.bsky.social · 18/10/2025

Andrew Zwicker - physicist & Representative

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Coleen Murphy @ctmurphy1.bsky.social · 18/10/2025

Checking in from the Princeton NJ No Kings rally

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Coleen Murphy @ctmurphy1.bsky.social · 08/06/2025

Apparently this is now Athena's favorite place to sleep and Dash's favorite chew toy - meanwhile the scratching post hasn't been touched Also: Abolish ICE

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Coleen Murphy @ctmurphy1.bsky.social · 07/06/2025

Of course the box is better than the toy

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Coleen Murphy @ctmurphy1.bsky.social · 05/06/2025

Jane Boyer read and annotated my book cover to cover! So impressive

Jane Boyer with annotation stickies throughout "How We Age"

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Coleen Murphy @ctmurphy1.bsky.social · 04/06/2025

Our model is that non-autonomous regulation of memory might be a good way to extend the memory function in times of stress on a longer timescale than neurons might provide, paralleling the effects seen from blood factors that are secreted from the liver that improve cognition (Horowitz, Villeda).

Non-autonomous signaling may allow a longer timescale of memory function than neuronal memory regulation - that could be important in times of low nutrients - and is dependent on CREB transcription

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Coleen Murphy @ctmurphy1.bsky.social · 04/06/2025

So why the hypodermis? We think that the hypodermis is not just skin; it is also a highly metabolic tissue, with a transcriptome that best matches the human liver and blood plasma.

The hypodermis is a highly metabolic tissue that transcriptionally resembles blood plasma and liver

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Coleen Murphy @ctmurphy1.bsky.social · 04/06/2025

Finally, we see that aged daf-2 mutants rely on CREB almost entirely for their extended memory span, so there is a shift from neurons using CREB-independent to CREB-dependent targets to extend memory.

Unlike young daf-2 mutants, ALL of older daf-2 mutants' memory extension is CREB-dependent

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Coleen Murphy @ctmurphy1.bsky.social · 04/06/2025

We found that CREB is required for about half of daf-2's short-term memory extension, and for all of hyp DAF-2 and OSM-11 overexpression memory extension

about half of daf-2's memory extension is gone when CREB is removed

CREB is required for all of hyp DAF-2's memory extension

All of osm-11 overexpression's memory extension requires CREB

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Coleen Murphy @ctmurphy1.bsky.social · 04/06/2025

When we used snSeq to figure out the signaling, we found that the CREB transcription factor is broadly upregulated in neurons, including “memory” neurons, as are CREB’s targets.

CREB/crh-1 is broadly upregulated, including in "memory" neurons like AIM

CREB's memory targets (Lakhina et al Neuron 2016) are also upregulated

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Coleen Murphy @ctmurphy1.bsky.social · 04/06/2025

In the neurons, Notch signaling components (receptor LIN-12 and transcriptional co-factors SEL-8 and LAG-1) are all required for hyp DAF-2 memory - so DAF-2 degradation in the hypodermis induces OSM-11 expression and signaling to Notch in the neurons

lin-12 in the RIG neuron is required for hyp DAF-2 memory

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Coleen Murphy @ctmurphy1.bsky.social · 04/06/2025

So, how is this skin-like tissue regulating memory? First, we sought the signal, and narrowed it down to the Notch ligand OSM-11, which is expressed in the hypodermis. Knocking osm-11 down prevents hypodermal DAF-2 memory, and overexpressing it improves memory.

osm-11 is a daf-2/daf-16 target expressed in the hypodermis that is upregulated in hyp DAF-2 but not neuronal DAF-2 degraded worms

Reduction of osm-11 prevents Hyp DAF-2 degradation-induced memory increase

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Coleen Murphy @ctmurphy1.bsky.social · 04/06/2025

Even more weirdly, gene expression changes caused by this regulation by daf-2 in neurons and hypodermis are totally different.

Venn diagram of whole-worm targets of DAF-2 degraded in hypodermis vs neurons shows little overlap

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Coleen Murphy @ctmurphy1.bsky.social · 04/06/2025

But we were totally surprised that reduction of daf-2 in the hypodermis GREATLY improved memory! And mid-life reduction of DAF-2 in the hypodermis also improves memory in aged worms.

DAF-2 degradation only in the hypodermis extends memory

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Coleen Murphy @ctmurphy1.bsky.social · 04/06/2025

Not surprisingly, reduction of daf-2 in neurons extended memory, while other tissues had no effect (including intestine, which regulates lifespan – so lifespan and memory are totally uncoupled).

Degradation of DAF-2 only in neurons extends memory, like daf-2 mutants

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Coleen Murphy @ctmurphy1.bsky.social · 04/06/2025

We previously found that long-lived insulin signaling daf-2 mutants also extend memory duration (Kauffman 2010, Kaletsky 2016) and memory span (Weng & Murphy, 2024). So when Meng-Qiu Dong asked us to test her tissue-specific DAF-2 strains (Zhang 2022) for memory, we were happy to.

daf-2 mutants have longer memory than wild-type (N2)

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Coleen Murphy @ctmurphy1.bsky.social · 23/04/2025

So we have three different pathogenic Pseudomonas species with three different small RNAs that have perfect 16-17nt matches to three different sequences in two genes (maco-1, vab-1) that act in the same genetic pathway to regulate daf-7 expression and the switch from attraction to avoidance.

We have three different pathogenic Pseudomonas species with three different small RNAs that have perfect 16-17nt matches to three different sequences in two genes (maco-1, vab-1) that act in the same genetic pathway to regulate daf-7 expression, ASI function, and the switch from attraction to avoidance.

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Coleen Murphy @ctmurphy1.bsky.social · 23/04/2025

PF15 training also induces avoidance of PA15, P. vranovensis, and the beneficial bacterium, P. mendocina, reinforcing the idea that these mechanisms overlap - but also that avoidance of PF15 prevents attraction to beneficial food sources, so could be good to forget!

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