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Using miniature guts grown in a dish and 3D biophysical modelling, FMI researchers and their collaborators have uncovered the forces that give the intestinal wall its classic brushlike appearance. The findings can help to understand how the gut takes form during development — and how this process goes awry in disease.

The spatial organization of the genome is fundamental for the regulation of our genes and has to be established de novo during early embryogenesis. By combining powerful Drosophila genetics with 3D chromosome modelling, a collaboration between the Giorgetti group at the FMI and the MPI of Immunobiology and Epigenetics in Freiburg revealed a critical role of the epigenetic regulator HP1 in the establishment of 3D genome organization in the early Drosophila embryo.

The protection of genome integrity of germ cells is essential for animal fertility. Researchers from the Grosshans group characterized a defense mechanism against selfish genetic elements in the C. elegans germline. They identified a protein processing mechanism that controls the activity of small RNAs to achieve specific silencing of transposons while sparing endogenous genes.

The brain's emotion-processing center — the amygdala — is one of several brain regions involved in social behavior. But the exact role that this almond-shaped structure plays in the so-called 'social brain' remains mysterious. Now, the Lüthi group has found that the activity of different populations of neurons in the amygdala reflects whether mice interact with their peers, or whether they focus on self-centered behaviors such as grooming.

During development, scores of molecular signals prod cells to take on specialized identities and functions. In response to some of these signals, the cellular machinery awakens specific genes called 'immediate early genes' within minutes. The Rijli group has now identified a unique molecular signature that keeps immediate early genes quiet yet poised for rapid activation.

Chromatin remodelers are needed to take nucleosomes away from DNA in order to make room for transcription factors to bind, and regulate the activity of our genes. It has been unclear how dynamic this process is. Researchers from the Schübeler group now revealed that active regulatory regions undergo continuous cycles of chromatin opening.

Transposons are foreign DNA elements capable of random insertion into the genome, an event that can be very dangerous for a cell. Their activity must be silenced to maintain genomic integrity, which is primarily achieved by H3K9me3-mediated repression. Researchers from the Gasser group identified two parallel pathways that are essential for H3K9me3- mediated transcriptional repression and thus for protecting the genome from toxic transposon activation.

Just like people, cells get stressed too. A sudden drop in oxygen, overheating, or toxins can trigger a cascade of molecular changes that lead cells to stop growing, produce stress-protective factors, and form stress granules - proteins and RNA molecules huddled together into membrane-less organelles.

How do molecules involved in activating our immune system discriminate between our own DNA and foreign pathogens? Researchers from the Thomä group, in collaboration with the EPFL, deciphered the structural and functional basis of a DNA-sensing molecule when it comes in contact with the cell's own DNA, providing crucial insights into the recognition of self vs.

Intestinal organoids recapitulate not only the structure of intestinal epithelium but also its ability to regenerate following damage. Using this research tool, the group of Prisca Liberali unraveled mechanisms orchestrating organoid formation and intestinal regeneration with a unique image-based screening approach.

DNA damage can occur anywhere in the genome, but most DNA is wrapped around nucleosomes making it inaccessible to the repair machinery. Researchers from the Gasser group now show that DNA damage induces histone depletion, which increases the accessibility and flexibility of the DNA fiber and enhances the rate of homology search during repair by homologous recombination.

The group of Helge Grosshans characterized the " C. elegans oscillator", over 3,700 genes that are rhythmically expressed during the larval development of C. elegans . They demonstrated the coupling of the oscillator with molting and got insights into how it is wired. Their findings suggest that the oscillator functions as a developmental clock with a developmental checkpoint function.

The cytosolic iron sulfur assembly (CIA) pathway is required for the insertion of Fe-S clusters into proteins, including many DNA replication and repair factors. Despite its essential cellular function, this pathway remains enigmatic. A new integrative structural and biochemical study from the Thomä group now provides detailed insights into the mechanisms of Fe-S protein biogenesis.

In a comprehensive study, researchers from the Rijli group found that a single Hox transcription factor expressed in a group of neurons of the pontine nucleus - the cerebral cortex most important brainstem relay to the cerebellum - determines the wiring onto these neurons of somatosensory cortical neurons, while avoiding visual cortical neurons.

While the first genome-wide DNA methylation map in mammalian cells was established over 10 years ago, such maps only provide snapshots and do not inform about the actual dynamics of this epigenetic mark. Researchers from the Schübeler group now quantified actual rates of methylation and demethylation for 860,404 individual CpGs in mouse embryonic stem cells.

The Peters group studies chromatin formation and regulation in mammalian germ cells and during early embryonic development. Now researchers from the group identified a novel pathway that is essential for maintaining the integrity of heterochromatin, and therefore for securing chromosome stability. Chromatin - made up of DNA wrapped up around histone proteins - plays a major role in gene regulation by modulating the accessibility of transcription factors to their target sequences in the genome.

The Gasser group discovered that silencing of heterochromatic regions - and more specifically of hundreds of Polycomb-target genes enriched for H3K27me3 - can occur through selective RNA degradation, and not only through transcriptional repression. The study links the epigenetics state of a gene with the fate of its RNA transcript.

Mutations in the nuclear structural protein lamin A produce rare, tissue-specific diseases called laminopathies. To study these diseases, researchers from the Gasser group introduced a mutation inducing a human laminopathy in C. elegans and monitored its effect on chromatin. Not only did they understand the molecular basis of the disease, they found a way to counteract the dominant defects of the mutation, suggesting a novel therapeutic pathway.

Scientists from the Friedrich group have developed a new virtual reality system that allows them to manipulate the sensory environment of adult zebrafish at will, while simultaneously analyzing neural activity. This approach can be used to explore how the brain processes complex sensory inputs and how it uses internal models of the world to control behaviors.

RNA decay plays a fundamental role in gene expression by controlling the quality and quantity of messenger RNAs. However, it has proved difficult to study and is still shrouded in mystery. Scientists from the Bühler group now uncovered key targets, components and functions of mammalian RNA decay pathways, and found that RNA decay is tightly connected to another crucial stage of gene expression: protein synthesis (translation).