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Si Lab

Our lab investigates how distinct experiences in time may result in lasting behavioral changes.

Research Summary

How are memories created?

Research Areas

Neuroscience, Molecular and Cell Biology, Systems Biology

Organisms

Fruit flies, Donated human brain

The Si Lab investigates how a transient experience produces a persistent change in behavior and how, among the many experiences an animal encounters, only some result in this modification.

The research focuses on a type of protein, prion-like proteins, that have the propensity to aggregate or cluster together into an amyloid state. Historically, clustering of prions or prion-like proteins has been associated with Alzheimer’s and other neurodegenerative diseases. However, the Si Lab has found that some prions have a positive side and are essential for long-term memory, contradicting the long-held assumption that protein aggregates in the brain cause memory loss.

The Si Lab discovered that CPEB, a protein with prion-like properties, may be at the center of a series of biochemical changes at the connection points between brain cells that form the basis for memory persistence. Working with the sea snail Aplysia, the lab demonstrated that neuronal activity generates prion-like CPEB aggregates that stabilize connections between neurons. The fruit fly version of CPEB, called Orb2, undergoes prion-like changes to establish a persistent “memory trace,” and that disrupting Orb2 impaired the formation of long-term memory in fruit flies.

Thanks to a partnership with the Department of Neurosurgery at the University of Kansas Medical Center and generous living donors, the Si Lab is also analyzing brain tissue samples donated from patients who have undergone brain surgery. These tissues provide a new invaluable way to study the human brain.

Principal Investigator

Kausik Si

Scientific Director

Stowers Institute for Medical Research

Get to know the lab

Rendering of fruit fly

Science

Orb2, an amyloid with a known biological function in the fruit fly brain was purified and described structurally, indicating that it may be able to adopt the shape of an amyloid as part of its normal and necessary function.

Group of people outside

Our Team


Why Stowers?

Why would you want to start your lab at Stowers? Freedom. Listen as Scientific Director Kausik Si explains why he is excited to be here every day.

Visit the Lab

Featured Publications

Cryo-EM structure of a neuronal functional amyloid implicated in memory persistence in Drosophila.

Hervas R, Rau MJ, Park Y, Zhang W, Murzin AG, Fitzpatrick JAJ, Scheres SHW, Si K. Science. 2020;367:1230-1234.

Amyloid-like Assembly Activates a Phosphatase in the Developing Drosophila Embryo

Nil Z, Millan RH, Gerbich T, Leal P, Yu Z, Saraf A, Sardiu M, Lange JJ, Yi K, Unruh J, Slaughter B, Si K. Cell. 2019;178:1403-1420 e1421.

Antimicrobial peptides modulate long-term memory ​

Barajas-Azpeleta R, Wu J, Gill J, Welte R, Seidel C, McKinney S, Dissel S, Si K. PLoS Genet. 2018;14:e1007440. doi: 1007410.1001371/journal.pgen.1007440.

Regulated Intron Removal Integrates Motivational State and Experience

Gill J, Park Y, McGinnis JP, Perez-Sanchez C, Blanchette M, Si K. Cell. 2017;169:836-848.e815.

Immediate perception of a reward is distinct from the reward's long-term salience

McGinnis JP, Jiang H, Agha MA, Perez Sanchez C, Lange JJ, Yu Z, Marion-Poll F, Si K. eLife. 2016;5:e22283. doi: 22210.27554/eLife.22283.

A Putative Biochemical Engram of Long-Term Memory

Li L, Sanchez CP, Slaughter BD, Zhao Y, Khan MR, Unruh JR, Rubinstein B, Si K. Curr Biol. 2016;26:3143-3156.


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