Publications by Felix Naef | EPFL Graph Search

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Translation elongation plays a key role in cellular homeostasis, and dysregulation of this process has been implicated in various diseases and metabolic disorders. Uncovering the causes of intragenic heterogeneity of translation, especially in contexts of different amino acid deprivations, could help increase our understanding of these disorders and pave the way for novel therapeutics. Ribosome profiling provides accurate measurements for the genome-wide ribosome footprints, which could be utilized to inves

In mammals, a hierarchically organized circadian timing system orchestrates daily rhythms of nearly all physiology. A master pacemaker in the brain’s suprachiasmatic nucleus (SCN) synchronizes subsidiary clocks in most peripheral organs. By driving anabolic and catabolic cycles of proteins, lipids, and carbohydrates and by detoxifying endo- and xenobiotic components, the liver plays an important role in adapting the metabolic needs to rest-activity rhythms. In keeping with these functions, the liver express

Single-cell RNA sequencing (scRNA-seq) reveals heterogeneity in circadian clock states across individual cells, yet accurately inferring circadian phase and distinguishing biological desynchrony from technical noise remains challenging. Here, we introduce scRitmo, a probabilistic framework that infers single-cell circadian phases from mRNA count data, providing both a point estimate and a posterior uncertainty for each cell. A simulation-calibrated variance decomposition separates the observed phase dispers

The circadian clock and associated feeding rhythms have a profound impact on metabolism and the gut microbiome. To what extent microbiota reciprocally affect daily rhythms of physiology in the host remains elusive. Here, we analyzed transcriptome and metab ...

The timing and duration of sleep results from the interaction between a homeostatic sleep-wake-driven process and a periodic circadian process, and involves changes in gene regulation and expression. Unraveling the contributions of both processes and their ...

Translation elongation plays an important role in regulating protein concentrations in the cell, and dysregulation of this process has been linked to several human diseases. In this study, we use data from ribo-seq experiments to model ribosome densities, ...

Cells need to reliably control their proteome composition to maintain homeostasis and regulate growth. How protein synthesis and degradation interplay to control protein expression levels remains unclear. Here, we combined a tandem fluorescent timer and pu ...

Cell differentiation and proliferation are fundamental to the development of multicellular organisms. While studies in various non-mammalian species show that development can proceed despite disrupted cell cycle progression, the extent to which normal cell cycle dynamics are required in mammals remains unclear. Using mouse gastruloids, we examined the effects of cell cycle inhibition on development. Despite near-complete growth arrest, gastruloids still underwent symmetry breaking, elongation, and germ laye

The circadian clock and the cell cycle are two biological oscillatory processes that coexist within individual cells. These two oscillators were found to interact, which can lead to their synchronization. Here, we develop a method to identify a low-dimensi ...

The circadian clock drives extensive temporal gene expression programs controlling daily changes in behavior and physiology. In mouse liver, transcription factors dynamics, chromatin modifications, and RNA Polymerase II (PolII) activity oscillate throughou ...

BACKGROUND: To understand cancer-related modifications to transcriptional programs requires detailed knowledge about the activation of signal-transduction pathways and gene expression programs. To investigate the mechanisms of target gene regulation by hum ...

In prokaryotes and eukaryotes, most genes appear to be transcribed during short periods called transcriptional bursts, interspersed by silent intervals. We describe how such bursts generate gene-specific temporal patterns of messenger RNA (mRNA) synthesis ...

Mammalian physiology resonates with the daily changes in the external environment, allowing processes such as rest-activity cycles, metabolism, and body temperature to synchronize with daily changes in the surroundings. Studies have identified the molecula ...

U2OS cells harbor a circadian clock but express only a few rhythmic genes in constant conditions. We identified 3040 binding sites of the circadian regulators BMAL1, CLOCK and CRY1 in the U2OS genome. Most binding sites even in promoters do not correlate w ...

Mammals have evolved an internal timing system, the circadian clock, which synchronizes physiology and behavior to the daily light and dark cycles of the Earth. The master clock, located in the suprachiasmatic nucleus (SCN) of the brain, takes fluctuating ...

BACKGROUND: The development of vertebrate limbs has been a traditional system to study fundamental processes at work during ontogenesis, such as the establishment of spatial cellular coordinates, the effect of diffusible morphogenetic molecules or the translation between gene activity and morphogenesis. In addition, limbs are amongst the first targets of malformations in human and they display a huge realm of evolutionary variations within tetrapods, which make them a paradigm to study the regulatory genome

Mammalian energy homeostasis depends on coordinated metabolism across tissues, with the liver acting as a central hub for systemic energy balance and biosynthetic precursor supply. Although hepatic mitochondrial dysfunction is implicated in diverse pathologies, mitochondrial regulation across liver microanatomical space and time remains incompletely defined. Here, we mapped how mitochondrial- and nuclear-encoded genes supporting mitochondrial function vary along spatial gradients within the lobule and acros

In eukaryotes, RNA is synthesised in the nucleus, spliced, and exported to the cytoplasm where it is translated and finally degraded. Any of these steps could be subject to temporal regulation during the circadian cycle, resulting in daily fluctuations of ...

Observing cellular responses to perturbations is central to generating and testing hypotheses in biology. We developed a massively parallel microchemostat array capable of growing and observing 1,152 yeast-GFP strains on the single-cell level with 20 min t ...

The mammalian liver is a central hub for systemic metabolic homeostasis. Liver tissue is spatially structured, with hepatocytes operating in repeating lobules, and sub-lobule zones performing distinct functions. The liver is also subject to extensive tempo ...

Felix Naef

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Conditional Deep Learning Model Reveals Translation Elongation Determinants during Amino Acid Deprivation

Daily liver rhythms: Coupling morphological and molecular oscillations

Inferring circadian phases and quantifying biological desynchrony across single-cell transcriptomes

The Mouse Microbiome Is Required for Sex-Specific Diurnal Rhythms of Gene Expression and Metabolism

Sleep-wake-driven and circadian contributions to daily rhythms in gene expression and chromatin accessibility in the murine cortex

Towards improving full-length ribosome density prediction by bridging sequence and graph-based representations

Single Live Cell Monitoring of Protein Turnover Reveals Intercellular Variability and Cell-Cycle Dependence of Degradation Rates

Cell-cycle inhibition preserves robust development but rebalances lineages in mouse gastruloids

Low-dimensional dynamics of two coupled biological oscillators

Oscillating and stable genome topologies underlie hepatic physiological rhythms during the circadian cycle

Relationship between estrogen receptor alpha location and gene induction reveals the importance of downstream sites and cofactors

Mammalian genes are transcribed with widely different bursting kinetics

Cross-regulatory circuits linking inflammation, high-fat diet, and the circadian clock

Non-Circadian Expression Masking Clock-Driven Weak Transcription Rhythms in U2OS Cells

Systems Chronobiology: Global Analysis of Gene Regulation in a 24-Hour Periodic World

Analysis of the dynamics of limb transcriptomes during mouse development

The hepatic mitochondrial landscape

Comprehensive analysis of the circadian nuclear and cytoplasmic transcriptome in mouse liver

A chemostat array enables the spatio-temporal analysis of the yeast proteome

Space-time logic of liver gene expression at sub-lobular scale