Cells, co-auth.:W.Wahli

The Opioid Receptor Influences Circadian Rhythms in Human Keratinocytes through the β-Arrestin Pathway

Paul Bigliardi 1 2Seetanshu Junnarkar 3Chinmay Markale 1 2Sydney Lo 1 2Elena Bigliardi 1 2Alex Kalyuzhny 4Sheena Ong 3Ray Dunn 3 5Walter Wahli 5 6 7Mei Bigliardi-Qi 1 2

. 2024 Jan 25;13(3):232.

 doi: 10.3390/cells13030232.


The recent emphasis on circadian rhythmicity in critical skin cell functions related to homeostasis, regeneration and aging has shed light on the importance of the PER2 circadian clock gene as a vital antitumor gene. Furthermore, delta-opioid receptors (DOPrs) have been identified as playing a crucial role in skin differentiation, proliferation and migration, which are not only essential for wound healing but also contribute to cancer development. In this study, we propose a significant association between cutaneous opioid receptor (OPr) activity and circadian rhythmicity. To investigate this link, we conducted a 48 h circadian rhythm experiment, during which RNA samples were collected every 5 h. We discovered that the activation of DOPr by its endogenous agonist Met-Enkephalin in N/TERT-1 keratinocytes, synchronized by dexamethasone, resulted in a statistically significant 5.6 h delay in the expression of the core clock gene PER2. Confocal microscopy further confirmed the simultaneous nuclear localization of the DOPr-β-arrestin-1 complex. Additionally, DOPr activation not only enhanced but also induced a phase shift in the rhythmic binding of β-arrestin-1 to the PER2 promoter. Furthermore, we observed that β-arrestin-1 regulates the transcription of its target genes, including PER2, by facilitating histone-4 acetylation. Through the ChIP assay, we determined that Met-Enkephalin enhances β-arrestin-1 binding to acetylated H4 in the PER2 promoter. In summary, our findings suggest that DOPr activation leads to a phase shift in PER2 expression via β-arrestin-1-facilitated chromatin remodeling. Consequently, these results indicate that DOPr, much like its role in wound healing, may also play a part in cancer development by influencing PER2.

Front Mol Biosci, Auth.: AM Cattaneo, group Benton

Heterologous investigation of metabotropic and ionotropic odorant receptors in ab3A neurons of Drosophila melanogaster

Johan Henning Pettersson 1Alberto Maria Cattaneo 1 2 3

. 2024 Jan 25:10:1275901.

 doi: 10.3389/fmolb.2023.1275901. eCollection 2023.


In insects, antennal ionotropic receptors (IRs) and odorant receptors (ORs) are among the main sensors of olfactory cues. To functionally characterize the subunits from these receptors, the use of ab3A neurons from transgenic Drosophila melanogaster represented one of the most powerful tools, allowing the identification of ligands (deorphanization) and decrypting their pharmacological properties. However, further investigation is needed to shed light on possible metabotropic functionalities behind insect olfactory receptors and test potentials from the up-to-now-used empty neuronal systems to express subunits belonging to variegate receptor classes. In this project, we adopted the most updated system of Drosophila ab3A empty neurons to test various olfactory receptors, ranging from human ORs working as metabotropic G-protein coupled receptors to insect ionotropic IRs and ORs. Testing transgenic Drosophila expressing human ORs into ab3A neurons by single sensillum recording did not result in an OR response to ligands, but it rather re-established neuronal spiking from the empty neurons. When transgenic D. melanogaster expressed ionotropic IRs and ORs, both heterologous and cis-expressed IRs were non-functional, but the Drosophila suzukii OR19A1 subunit responded to a wide asset of ligands, distinguishing phasic or tonic compound-dependent effects. Despite the use of Drosophila ab3A neurons to test the activation of some metabotropic and ionotropic receptor subunits resulted non-functional, this study deorphanized a key OR of D. suzukii demonstrating its binding to alcohols, ketones, terpenes, and esters.

CIG minisymposium: SNSF Starting grant candidates


December 13

GENOPODE Auditorium A

8:30 Babatunde Ekundayo Accessing DNA in condensed chromatin: Fundamental mechanisms and implications for gene therapy

9:10 Akanksha Jain TBD


10:20 Ehsan Habibi Deciphering the Principles of Embryo Development Across Space and Time  

11:00 Yoav Voichek Transcriptional Regulation in Plants – Unique Properties and Principles

December 14

GENOPODE Auditorium B

8:00 Ricardo Bocchi Molecular mechanisms underlying astrocyte origins and diversity

8:40 Irene Beusch Exploring functions of spliceosomal proteins through CRISPR-Cas9 base editing screens

9:20 Alessandra Brambati DNA Double-Strand Breaks: Drivers of Disease and Evolution

Johannes Larsch and Martina Legris got an SNSF starting grant



Johannes Larsch, an assistant Professor at the CIG, and Martina Legris, a postdoctoral fellow in Christian Fankhauser group, both got an SNSF starting grant. Martina will join the University of Neuchâtel, and Johannes will use this grant on his project at the CIG.