How a single kinase switch dissociates sleep depth, quantity, and circadian timing
Audience: Member of University - ALL Format: In PersonFriday, 3 July 2026, 3pm to 4pm
CNCB Seminar
Speaker(s): Staci Jakyong Kim (KAIST)
Series: CNCB Seminar Series
Venue:
Sherrington Building - Sherrington Library
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Sherrington Library Sherrington Building off Parks Road Oxford Oxfordshire OX1 3PT United Kingdom
Department: Physiology Anatomy and Genetics (Department)
Organiser: Fiona Woods
Host: Haram Park
More info:
The two-process model describes sleep as the interplay of a homeostatic drive and a circadian process, yet the physical substrate that stores and reads out sleep need has remained elusive. Through an unbiased forward-genetic screen in mice, we identified Salt-Inducible Kinase 3 (SIK3) and Histone Deacetylase 4 (HDAC4) as central regulators of sleep. The SIK3–HDAC4 signaling axis acts as a kinase-controlled molecular switch governing sleep amount and depth. This regulation generalizes across paralogues and across kinase inputs, and runs in both directions. A phospho-resistant mutation in HDAC5, the close paralogue of HDAC4, reproduces the HDAC4 phenotype: both bias the repressor toward the nucleus, increase repression of sleep-promoting genes, and reduce NREM sleep and delta power. Conversely, reducing HDAC4 dosage relieves repression and increases sleep. A second kinase, CaMKII, converges on the same HDAC4 node through distinct phosphorylation sites, extending the switch to a second upstream pathway. Previous evidence that this axis may couple sleep state to physiology beyond the sleep circuitry itself point toward the broader question now driving the lab: how a compact set of phosphoregulated switches links the molecular machinery of sleep to the circuit-level control of brain state, and to the longer arc of brain and body health.