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The Groundbreaking Discovery at Stowers Institute
Researchers at the Stowers Institute for Medical Research in Kansas City, Missouri, have unveiled a pivotal mechanism in how the brain transforms fleeting experiences into enduring memories. This breakthrough centers on a previously overlooked tiny protein known as Funes, a micropeptide that acts as a molecular chaperone. Published in the Proceedings of the National Academy of Sciences (PNAS) on January 30, 2026, the study provides the first direct evidence that the nervous system intentionally forms amyloid structures to store long-term memories.
Led by Scientific Director Kausik Si, Ph.D., the Si Lab team built upon over a decade of work exploring prion-like proteins in memory. Their findings challenge the long-held view of amyloids solely as villains in neurodegenerative diseases like Alzheimer's, revealing their beneficial role when precisely regulated.
Understanding Memory Formation: From Synapses to Stability
Memory formation begins at the synapse, the junction between neurons where electrical signals convert to chemical ones. Short-term memories rely on transient changes, but long-term memories require structural remodeling for persistence. This process, known as long-term potentiation (LTP), strengthens synaptic connections, but how these changes endure remained elusive.
The brain must select which experiences merit permanence amid constant sensory input. The Si Lab's research pinpoints functional amyloids—self-assembling protein fibrils—as the stable scaffold. Unlike pathological amyloids that clump destructively, these are activity-triggered and localized.
Amyloids: From Disease Markers to Memory Architects
Amyloids are proteins that fold into beta-sheet-rich fibrils, historically infamous for roles in Alzheimer's (amyloid-beta plaques), Parkinson's, and Huntington's. Yet, nature employs amyloids functionally in yeast prions for inheritance and bacterial biofilms for adhesion.
In the brain, the protein CPEB (cytoplasmic polyadenylation element-binding protein), or Orb2 in fruit flies, was implicated in 2012 by Si's team as a prion-like engram. Orb2 aggregates post-learning, locally translating mRNAs to maintain synaptic strength. The new study identifies Funes as the regulator preventing random aggregation.
Unveiling Funes: The Tiny Chaperone Protein
Funes, a J-domain-containing chaperone (first mention: J-domain protein family assists protein folding), was discovered by screening 30 chaperones in Drosophila mushroom bodies—the fly's memory hub. Overexpressing candidates and training flies on odor-sugar associations revealed Funes boosts long-term memory (24+ hours).
- Funes binds unstable Orb2 monomers, inhibiting basal fibrillation.
- Learning-induced neuronal activity releases Orb2, allowing Funes-guided seeding into ordered amyloids.
- This step-by-step: monomer binding → seed formation → fiber elongation → synaptic stabilization.
"I wanted to understand how unstable proteins help create stable memories," Si explained. Human Funes homologs link to schizophrenia, hinting broader roles.
Experimental Models: From Flies to Mammals
The team used Drosophila for genetic tractability, Aplysia californica (sea slug) for giant synapses mimicking sensorimotor plasticity, and cultured mouse neurons. Techniques included:
- Thioflavin-T staining for amyloid detection.
- Electron microscopy visualizing Funes-Orb2 fibers.
- Behavioral assays: flies forgetting odors without Funes, retaining with overexpression.
- FRAP (fluorescence recovery after photobleaching) showing amyloid stability.
Cross-species conservation: Mouse CPEB3 forms similar regulated amyloids, suggesting universality.
Aplysia studies confirmed Funes-like chaperones gate amyloid in gill-withdrawal reflex memory.Stowers Institute press release
Building on a Decade of Si Lab Innovations
Si's 2012 Science paper proposed CPEB prions for memory. 2016 Current Biology identified Orb2 aggregates as engrams predicting recall strength. 2020 cryo-EM resolved neuronal amyloid structure. This PNAS work completes the regulatory circuit.
Stowers, founded 2000, excels in non-university model organism research, fostering graduate programs and collaborations.
Postdoc opportunities in neuroscience abound at institutes like Stowers.Implications for Brain Health and Neurodegenerative Diseases
This dual amyloid nature—beneficial vs toxic—offers therapeutic hope. Dysregulated chaperones may underlie Alzheimer's amyloid-beta overaccumulation. Targeting Funes-like proteins could enhance memory or clear pathological forms selectively.
Statistics: 6.7M US Alzheimer's cases (2023), projected 13.8M by 2060. Functional amyloid insights may refine anti-amyloid drugs like lecanemab, avoiding memory side effects.
| Amyloid Type | Role | Example Disease |
|---|---|---|
| Functional | Memory storage | None |
| Pathological | Synaptic toxicity | Alzheimer's, Parkinson's |
Stakeholders: NIH funds such basic research; pharma eyes translation.GEN coverage
Stakeholder Perspectives and Expert Opinions
Kausik Si: "The research forces us to rethink... amyloid formation in the brain." Neuroscientists praise the rigor; critics note animal-to-human translation challenges. Alzheimer's Association welcomes amyloid nuance.
- Benefit: Precise memory enhancers for aging.
- Risk: Unintended amyloid promotion.
- Solution: Chaperone-specific drugs.
Future Outlook: Next Frontiers in Memory Research
Upcoming: Human brain organoids testing Funes orthologs; AI modeling amyloid dynamics; clinical trials modulating chaperones. Stowers plans conferences on amyloids (April 2026).
Timeline: 5-10 years to therapeutics; immediate impact on basic neuroscience curricula.
Career Opportunities in Memory and Neuroscience Research
This discovery spotlights demand for experts in molecular neuroscience. US universities like Harvard, Stanford, and UCSF seek postdocs, faculty in amyloid/memory labs. Research assistant jobs in Drosophila/mammalian models proliferate.
Actionable: Network via SfN; pursue PhDs at Stowers Graduate School. Salaries: Postdoc $60K+, Prof $150K+.Professor salaries data
Conclusion: A New Chapter in Brain Science
The Funes discovery illuminates memory's molecular poetry, blending instability into permanence. For academics eyeing professor ratings, higher ed jobs, or career advice, this exemplifies cutting-edge research driving progress. Explore university jobs or post a job to join the quest.
Stay informed: amyloid research promises revolutions in cognition and disease treatment.
