The Naef Lab

🕰️ The 'Towards clinically actionable molecular biomarkers of the circadian clock' symposium in Venice has just kicked off. Looking forward to insightful discussions ahead! #CircadianResearch #WarwickInVenice

In humans, low hepatic #VLDLR expression correlates with a medical history of heart attack, and with atherosclerosis severity. (4/5)

Conversely, VLDL particle generation shows a periportal bias. (3/5)

We showed that the #VLDL receptor is restricted to the area around hepatic pericentral veins, with much higher mRNA and protein expression in female mice and women compared to male counterparts. (2/5)

How do our internal 24h #rhythms change across sex and age? @lollotala and @TebogCirdec’s paper is now out in @ScienceMagazine. Congrats to everyone for this stimulating project! science.org/doi/10.1126/scie… #circadian #gtex #aging

Amazing colors this week coming to @epflSV

Then we stratified by age, and to our surprise the core clock was conserved. In contrast, rhythmic programs overall were strongly dampened in aged donors, with almost a 10-fold decrease in the number of rhythmic genes with amplitudes higher than two log2 units. (9/n)

The adrenal gland exhibited marked female-specific rhythmic mRNA levels centered at midday (GR targets suggestive of autocrine signaling); an early night heat shock stress response was supported both by mRNAs and predicted HSF1 transcription factor activity. (8/n)

We compared the core clock across sex, which showed that the structure of the genes was indistinguishable, however the number of rhythmic genes was globally higher in females by a factor of about 30%. (6/n)

DIPs also allow assessing genome-wide rhythmicity across tissues. These 24h rhythmic programs showed morning (7am) and evening (7pm) waves of gene expression throughout the body, with metabolic tissues harboring the most and brain tissues the least rhythmicity. (5/n)

Using DIPs, we found that core clock genes behave similarly to mice, and were tightly synchronized across the human body with a spread of ~2 hours (adrenal gland peaking first). (4/n)

Using a new algorithm, we inferred for each donor one reliable Donor Internal Phase, DIP. These DIPs allowed us to study 16k samples from 46 tissues and 914 donors giving a full-body view of rhythmic transcripts in humans. (3/n)

More of the same in the replies: "We find that Bmal1 is also rhythmic in Bma1l+/+ tissue, as is Cry2 (Fig. 1B)." q=0.005!

Very swiss

If true, that sounds pretty worrisome... (air quality in 2/3 of swiss classrooms is bad) we should be able to do better than that

Looking for an exciting #postdoc in #circadian #biology and/or quantitative gene regulation? Available #position at Naef-lab epfl.ch/labs/naef-lab #epfl @epfl_SV. Apply now: goo.gl/4BRjJX or goo.gl/X7gmCf. #generegulation #ribosome #singlecell #omics Pls RT

🚴‍♂️ to the lab @epfl_en every morning #biketowork. 4 months past already in 2018... One shot every morning, beautiful Lac Léman @SustainableLake. What a treat. Long winter this year, finally it's spring! Next update end of the summer.