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How does the brain make memory?

Atomic structure of biochemically active Orb2 amyloid reveals the stacked three-fold helical symmetry of the filament core.

Our Research

We wish to understand how a temporally restricted experience produces a persistent change in behavior and how, among the myriad experiences an animal encounters, only some produce persistent change in behavior.

Our work has provided a plausible biochemical mechanism addressing both issues. We have observed that the prion-like behavior of a neuronal RNA binding protein, CPEB, is required for the persistence of memory. The unique biophysical and functional properties of neuronal CPEB have now allowed us ask four key questions:

  • Where does prion-like conversion occur (site of memory formation?
  • What determines the engagement of the prion-like process?
  • How does this process occur (the specificity of memory formation)?
  • What happens to the prion-like species when memory decays (the basis of forgetting)?

We are also exploring the possibility that prion-based protein conformational switches may be utilized in other biological contexts to allow temporally restricted stimuli to produce persistent changes. We have carried out a systematic search of functional prion-like proteins in D. melanogaster and have identified a discrete number of proteins with the potential to be functionally prion-like. We are trying understand what specific function does the prion-like state of these proteins serve and how are they regulated.

Lab Philosophy

Kausik Si, Ph.D, discusses his lab philosophy and approach to science.

News from the Lab

Learn more about what's happening in the Si Lab

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