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Reconstructing structure and function of a neuronal circuit The function of neuronal circuits is thought to be determined largely by specific connections between neurons. But this assumption has been difficult to test because the reconstruction of the synaptic connectivity of a neuronal circuit - its "wiring diagram" - is a major challenge.

Thanks to their expertise in single-molecule imaging of RNAs, researchers from the group of Jeff Chao at the FMI helped to reveal the biological mechanism of a small molecule that restricts Ewing's sarcoma cell growth. The study - published - is further evidence that each step of the gene expression pathway may be druggable, and a great example of a Novartis-FMI collaboration.

How does the brain control the mechanisms of memory so that it only remembers major events in a constantly changing environment? The group of Andreas Lüthi has now described a fundamental neuronal microcircuit that allows mice to learn about unexpected important events and adapt their behavior accordingly.

Animals are able to attach simple ratings to complex objects in their environment to guide behavior. For example, humans can easily tell whether they like a wine or not, which will influence their future choices in the wine store. Similarly, animals can tell whether a complex odor is good or bad in order to decide whether to approach or avoid it.

The organization of chromatin in the three-dimensional space is complex and requires the help of many proteins, including CTFC. Researchers from the group of Marc Bühler have identified a new player in the process: the transcription factor ADNP. In a recent study, they show that ADNP competes with CTFC, acting as a local modulator of chromatin looping.

Although predisposing processes occur earlier, schizophrenia breaks out at young adulthood, suggesting it might involve a pathological transition during late brain development in predisposed individuals. Using a genetic mouse model of schizophrenia, researchers from the Caroni group at the FMI showed that, like in patients, characteristic network and cognitive deficits only emerge in adult mice.

Deubiquitinases (DUBs) play a general role removing protein-degrading ubiquitins throughout the cell and are not typically known for specificity. Analyzing the two protein complexes BRISC and BRCA1-A, which have the same DUB core but play different roles in human biology, the Thomä group - in a collaboration with the Novartis Institutes for BioMedical Research (NIBR) - showed that DUBs can have diversified targeting and regulatory functions.

The protein TRIM71 is an important regulator of animal development and plays a role in various diseases. In close collaboration, scientists from the groups of Helge Grosshans and Marc Bühler at the FMI elucidated the mechanism by which TRIM71 binds and turns off its RNA targets. They also identified several core targets of TRIM71, including proteins involved in genetic disorders.

The Friedrich Miescher Institute for Biomedical Research is a leader in the field of DNA and RNA research. DNA has become the icon of modern bioscience but few people realize that it was our namegiver, who - almost a century before Watson and Crick - laid the chemical groundwork for the molecular breakthroughs that followed.

Characterizing chromosome structure is fundamental to a better understanding of gene expression. Current experimental methods helped to build mechanistic models of chromosome folding, however they could not be formally validated so far by independent techniques. This is what the Giorgetti group just did - thanks to a new method they developed to measure chromosome structure quantitatively in living cells.

May 30, 2019 UV light damages the DNA of skin cells, which can lead to skin cancer. But this process is counteracted by the DNA repair machinery, acting as a molecular sunscreen. It has been unclear, however, how repair proteins work on DNA tightly packed in chromatin, where access to DNA damage is restricted by protein packaging.

May 22, 2019 From yeast to man, the genome is partitioned into subnuclear compartments, with active euchromatin spatially separated from silent heterochromatin, which is often found at the nuclear periphery. This spatial distribution correlates with gene expression and contributes to cell-type integrity.

April 25, 2019 Intestinal organoids are three-dimensional structures derived from a single intestinal stem cell. They are great tools for applications ranging from fundamental biology to personalized and regenerative medicine. However, despite their relevance in research, it is still unclear how a single cell can give rise to a fully formed organoid.

April 23, 2019 Our actions are driven by "internal states" such as anxiety, stress, hunger or thirst - which will strongly affect and motivate our behaviors. Not much is known about how such states are represented by complex brain-wide circuits, including sub-cortical structures such as the amygdala.

April 17, 2019 Chromatin remodelers have the ability to move nucleosomes, which represent a physical barrier for access to DNA. Work by the group of Dirk Schübeler helps to better understand how remodelers orchestrate the global organization of nucleosomes in mammals. In a study published in Nature, the researchers uncovered how two classes of remodelers selectively mediate the binding of distinct transcription factors.

Puberty is a period of extensive changes of body morphology and function. As much as we are familiar with these life-altering changes, relatively little is known about what sets the whole process in motion. Thanks to studies in the tiny worm C. elegans , the group of Helge Grosshans is getting closer to understanding how the onset of puberty is genetically controlled.

Epigenetic memory of transcriptional gene silencing has been observed in several organisms. However, it was not known whether mechanisms exist that convey transgenerational memory of a silencing "experience", without silencing the gene permanently. The Bühler group has now found such a phenomenon in a unicellular organism.

The heterochromatin of eukaryotes contains repetitive DNA, which can lead to genome instability when transcribed. These sequences are normally silenced through the methylation of lysine 9 in histone H3 (H3K9me). Researchers from the Gasser group explored the role and importance of H3K9me. In two recent publications, they shed light on how the process is regulated and how loss of H3K9me renders cells sensitive to the loss of the breast tumor suppressor, BRCA1.

Transcription of our genes mostly begins in regions of the genome called CpG islands. These are rich in the dinucleotide CpG (thus the name), critical for gene activity and devoid of DNA methylation. Despite the relevance of CpG islands, it is unclear if the CpG dinucleotide itself contributes to their activity.

Two hallmarks of the integrated stress response of cells are the inhibition of translation and the formation of stress granules (SGs) and processing bodies (PBs). However, it is not well understood how both processes are coupled. In a study published in Molecular Cell, researchers from the Chao group applied single-molecule RNA imaging to study the interactions of mRNAs with SGs and PBs, and found out that the generally accepted assumptions about the function of granules need to be revised.