Sleep is a universal and complex physiological phenomenon, regulated by the interaction of circadian and homeostatic processes, as proposed by the two-process model. In our previous work, using a multi-omics approach, we found that while the circadian clock supplies mouse brain synapses with numerous transcripts in a time-of-day-dependent fashion, the translation into protein as well as their subsequent phosphorylation, is regulated by the homeostatic process. This exposes a binary molecular regulation that balances cellular energy and synaptic activity at opposite times of day.
Our current work, employing quantitative proteomics, focuses on investigating the role of circadian and sleep-wake signals in two areas:
1) synaptic function within defined neuronal populations across different brain regions, in collaboration with the group of Antoine Adamantidis (University of Bern) and supported by a Sinergia grant from the Swiss National Science Foundation (SNSF)
2) the dynamic protein composition of other subcellular compartments, beyond synapses, in diverse brain cell type. This work is done in collaboration with the group of Angel Barco (Institute for Neuroscience, Alicante, CSIC) and funded by the Chan Zuckerberg Initiative Neurodegeneration Challenge Network (NDCN).
ElGrawani, W, Sun, G, Kliem, FP, Sennhauser, S, Pierre-Ferrer, S, Rosi-Andersen, A, Boccalaro, I, Bethge, P, Heo, WD, Helmchen, F, Adamantidis, AR*, Forger, DB*, Robles, MS* and Brown, SA* (2024). BDNF-TrkB signaling orchestrates the buildup process of local sleep. Cell reports, 43(7), 114500. doi.org/10.1016/j.celrep.2024.114500 * Equal contribution
Kliem FP, Brüning F, Robles MS (2022) Proteomics Approaches to Assess Sleep and Circadian Rhythms. Circadian Clocks. Neuromethods doi.org/10.1007/978-1-0716-2577- 4_15
Brüning F, Noya SB, Bange T, Koutsouli S, Rudolph JD, Tyagarajan SK, Cox J, Mann M, Brown SA*, Robles MS*. (2019) Sleep-wake cycles drive daily dynamics of synaptic phosphorylation. Science. doi: 10.1126/science.aav3617 *co-corresponding author
Noya SB, Colameo D, Brüning F, Spinnler A, Mircsof D, Opitz L, Mann M, Tyagarajan SK*, Robles MS*, Brown SA*. (2019) The forebrain synaptic transcriptome is organized by clocks but its proteome is driven by sleep. Science. doi: 10.1126/science.aav2642*co- corresponding author