science wire

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.

In order to examine how synaptic inputs to individual neurons are organized in a distributed memory network, researchers from the Friedrich group performed electrophysiological recordings in the zebrafish homolog of the olfactory cortex. They found that large excitatory inputs were paired with large inhibitory inputs, which may seem counterintuitive because inhibition cancels excitation.

The European Research Council (ERC) has awarded a prestigious ERC Synergy Grant - perhaps the most competitive funding scheme from ERC - to the research groups of Prof. Filippo Rijli from the

As in previous years, several internal prizes were awarded during the FMI Annual Meeting, a 3 day scientific meeting attended by most scientists in the institute.

In a collaboration, Matthias Heindorf (FMI/Biozentrum), Silvia Arber (FMI/Biozentrum), and Georg Keller (FMI) investigated the role of motor cortex in the control of movement. Their study - published in 'Neuron' today - demonstrates that motor cortex is necessary for the execution of corrective movements in response to unexpected changes of sensory input but not when the same movements are executed spontaneously.

This summer four FMI postdocs have been awarded an EMBO fellowship and one an HFSP fellowship. These fellowships spark huge interest among young researchers but are rare, and hard to get.

Botond Roska from the Friedrich Miescher Institute for Biomedical Research and the Institute of Molecular and Clinical Ophthalmology in Basel is the recipient of the 2018 Bressler Prize.

Helge Großhans and his group at the Friedrich Miescher Institute for Biomedical Research (FMI) have elucidated the mode of action of the RNA-binding protein and stem cell factor LIN41. In an animal model, they showed that LIN41 silences four specific mRNAs, by two distinct mechanisms. They found that the choice of mechanism is determined by where on the mRNA LIN41 binds.

Scientists in the group of Andreas Lüthi have identified two neuronal circuits that mediate the association of contextual information with emotional memories. In their publication in Cell, they describe networks of neurons that are active in the hippocampus and the amygdala, when we associate for example an unpleasant situation with a certain place.

One of the fundamental questions in neuroscience is how neuronal circuits are wired to process information. The research group led by Rainer Friedrich has developed new methods to determine the complex morphology of densely packed neurons and their synaptic connections by 3D electron microscopy. As reported , these methods allowed them to reconstruct the entire olfactory bulb of a zebrafish larva, comprising more than 1000 neurons.

Understanding learning and memory processes is of fundamental importance to the study of brain function and provides valuable insights for disorders where these processes are disturbed. The current study of Pico Caroni from the Friedrich Miescher Institute for Biomedical Research, identifies plasticity induced at the time of learning, which is necessary during 12-14 hours after acquisition for long-term memory formation.

A better knowledge of RNA metabolism is key to understanding how RNAs regulate development and differentiation, and how their malfunction leads to disease. A team led by Helge Grosshans of the Friedrich Miescher Institute for Biomedical Research (FMI) has now identified a novel and evolutionarily conserved mechanism that preserves the stability of RNases and keeps them poised for RNA processing and degradation.

Understanding how different cell populations arise within a tumor - so-called tumor heterogeneity - is widely regarded as a major challenge for cancer biology. Mohamed Bentires-Alj and his group at the FMI have discovered how the most frequent mutation in human breast cancer leads to tumor heterogeneity.

Andreas Lüthi, Botond Roska, Dirk Schübeler and Nicolas Thomä, leading scientists at the Friedrich Miescher Institute for Biomedical Research in Basel, will each receive one of the prestigious ERC Advanced Grants from the European Research Council (ERC).

Marc Bühler and his team at the Friedrich Miescher Institute for Biomedical Research (FMI) have elucidated the mechanism underlying small RNA-mediated gene silencing, thus solving a mystery which has been puzzling the research community for over a decade. Back in 2002, the discovery by several research groups that small RNA molecules can shut down clearly defined genome regions was hailed by Science as the Breakthrough of the Year.

Jeff Chao, Junior group leader at the FMI, together with colleagues in New York and Heidelberg, has developed a sophisticated technique that makes it possible to monitor the precise time and place of the first translation event within a cell. This novel method, known as TRICK, is described and initial results are reported in Science today.

Neurobiologists at the Friedrich Miescher Institute for Biomedical Research (FMI) have shown that neurons critical for learning can be divided into two subpopulations with different functions. Almost as if learning processes in the brain mimicked machine learning, one subpopulation is responsible for collecting a broad range of potentially relevant information, while the second subsequently helps to consolidate a successful strategy.

It has generally been believed that microRNAs control biological processes by simultaneously, though modestly, repressing a large number of genes. But in a study published in Developmental Cell, a group of scientists led by Helge Grosshans have now shown that miRNAs can control the development of a roundworm through regulation of a single target.

Vision - so crucial to human health and well-being - depends on job-sharing by just a few cell types, the rod cells and cone cells, in our retina. Botond Roska and his group have identified a novel function for rod photoreceptor cells in the retina in daylight. Driven by cones and mediated by horizontal cells, rods help to increase contrast information at times when they are not directly sensing light.

Patrick Matthias from the FMI, together with scientists from the ETH Zurich, has discovered that the influenza virus takes advantage of the cellular process that deals with misfolded proteins, to crack open its capsid. They could show that the viral capsid, by carrying unanchored ubiquitin, mimics misfolded protein aggregates.

Mohamed Bentires-Alj and his team at the Friedrich Miescher Institute for Biomedical Research (FMI) together with scientists from the Novartis Institutes for BioMedical Research (NIBR) show in a study that a promising therapeutic approach for metastatic breast cancer elicits deleterious effects after cessation of the treatment.

Rafal Ciosk and his group at the FMI have identified an important regulator of the transition from germ cell to embryonic cell. LIN-41 prevents the premature onset of embryonic transcription in oocytes poised for embryonic development, thus ensuring a successful passage between generations. This finding also holds promise for efforts to reprogram differentiated human cells into induced pluripotent stem cells.

Large molecular motors consisting of up to a dozen different proteins regulate access to the genome, which is essential for the transcription of genes and for the repair of DNA damage.

Nancy Hynes and her group at the Friedrich Miescher Institute for Biomedical Research have discovered an important mediator of breast cancer metastasis. The protein called Memo is not only required for cell migration and invasion, it is also an excellent prognostic marker for poor patient outcome and points the way to new therapeutic approaches.

Witold Filipowicz and his team have discovered how microRNAs repress translation of mRNAs. In a structure-function study published in Molecular Cell, they report different modes of recruitment of the CCR4-NOT complex to mRNAs targeted by microRNAs. They also demonstrate that CCR4-NOT recruits and activates the ATPase DDX6, an important translational inhibitor.

Learning can only occur if certain neuronal "brakes" are released. As the group led by Andreas Lüthi at the Friedrich Miescher Institute for Biomedical Research has now discovered, learning processes in the brain are dynamically regulated by various types of interneurons. The new connections essential for learning can only be established if inhibitory inputs from interneurons are reduced at the right moment.

Structural biologists at the Friedrich Miescher Institute for Biomedical Research have resolved the 3D structure of a protein machine that plays an important part in the maintenance of genomic stability. They have revealed how one unit of the machine, RMI, modulates the workings of an enzyme, topoisomerase III? (TopIII?), thus allowing double Holliday junctions - key intermediates in DNA repair - to be disentangled.

Motor commands issued by the brain to activate arm muscles take two different routes. As the research group led by Professor Silvia Arber at the Basel University Biozentrum and the Friedrich Miescher Institute for Biomedical Research has now discovered, many neurons in the spinal cord send their instructions not only towards the musculature, but at the same time also back to the brain via an exquisitely organized network.

Neurobiologist from the Friedrich Miescher Institute for Biomedical Research show how a network of neurons in hippocampus and cortex switches states to turn on and off learning in the adult. They further show how a stimulating environment promotes this switch, and thus learning. Their findings are published today in the renowned journal Nature and have far reaching implications also for diseases where learning and memory is impaired, such as Alzheimer's or dementia.

Neurobiologists at the Friedrich Miescher Institute identify a novel feature of the olfactory system that resembles functions engineered for digital cameras. Interneurons in the olfactory bulb stabilize odor-encoding neural activity patterns when the intensity of an odor stimulus varies over a large range.

Neurobiologist from the Friedrich Miescher Institute for Biomedical Research proved that excitability protects motoneurons from degeneration in amyotropic lateral sclerosis, a rare neurodegenerative disease. By modulating excitability they could influence the rate of motor dysfunction and muscle denervation, and slow the progression rate of the disease.

FMI scientists have identified a novel inhibitor, which synergizes with low-doses of other DNA damaging agents, to induce a dramatic chromosome fragmentation even in normal cells. Unexpectedly, the compound acts an as inhibitor of a large kinase complex called TORC2, which regulates actin polymerization.

Neurobiologists from the Friedrich Miescher Institute for Biomedical Research have been the first to measure the concerted activity of a neuronal circuit in the retina as it extracts information about a moving object. With their novel and powerful approach they can now not only visualize networks of neurons but can also measure functional aspects.

Scientists at the Friedrich Miescher Institute for Biomedical Research have identified a novel and unexpected regulatory activity of RNA at the edge of inactive chromosomal regions. In their publication they showed that non-protein coding RNAs demarcate active and inactive chromosomal regions by evicting the proteins necessary for the spreading of repressive chromatin marks.

Under the leadership of Nancy Hynes, scientists from the Friedrich Miescher Institute for Biomedical Research have identified a potential novel target for breast cancer treatment. The scientists could show that breast cancer patients with high levels of the receptor tyrosine kinase Ret have a worse prognosis; and that blocking Ret not only decreases tumor growth but also impacts the potential of the cancer to spread throughout the body.

In a comprehensive study, scientists at the Friedrich Miescher Institute for Biomedical Research identified the molecular logic underlying the retention of histones and their marks during the development of the sperm. These findings set the stage to address a fundamental question in epigenetics: whether and how chromatin marks in sperm are passed on to the next generation and contribute the epigenetic inheritance of traits shaped by experience or the environment.

A team of scientists at the Friedrich Miescher Institute for Biomedical Research and the University of Geneva has functionally dissected the molecular processes that ensure the stability of chromosomes.

Scientists from the FMI have identified a molecular mechanism that may explain how early pregnancy reduces the risk for breast cancer. Their Early pregnancy is the best protective agent against breast cancer. Very young mothers are particularly protected: Their lifelong breast cancer risk is cut in more than half when compared to other women.

Using the fruit fly as a model organism, neurobiologists from the Friedrich Miescher Institute for Biomedical Research have identified the L1-type CAM neuroglian as an important regulator for synapse growth, function and stability. They show that the interaction of neuroglian with ankyrin provides a regulatory module to locally control synaptic connectivity and function.

Scientists from the FMI identify how a family of proteins reads the methylation marks on the DNA so critical for cell development. These MBD proteins bind directly to methylation marks and inactivate the respective stretches of DNA. The findings are important because they provide the means to better understand how this epigenetic mark influences cell fates.

Neurobiologists at the FMI have been able to dissect a mechanism in the retina that facilitates our ability to see both in the dark and in the light. They identified a cellular switch that activates distinct neuronal circuits at a defined light level. The switch cells of the retina act quickly and reliably to turn on and off computations suited specifically for vision in low and high light levels thus facilitating the transition from night to day vision.

Scientists from the Friedrich Miescher Institute for Biomedical Research identify a novel mechanism in early germ cell development. They show how the chromatin modulator PRC1 coordinates the timing of sexual differentiation of germ cells during embryonic development. The study, which enhances our understanding of the mechanisms regulating stem-ness and cell fate determination, is published .

Neurobiologists at the Friedrich Miescher Institute for Biomedical Research (FMI) are the first to show that directional migration of neurons during brain development is controlled through epigenetic processes. In an elaborate study bridging epigenetics and neurobiology, the scientists found that the migratory pattern is orchestrated through epigenetic regulation of genes within neurons and spatial signals in the environment.

Scientists discovered how resistance mechanisms arise during the treatment of incurable metastatic breast cancer and suggest strategies to circumvent these by a combination therapy. Triple-negative breast cancers are the bad guys among the different types of breast cancer. They affect younger women, metastasize more easily, are tougher to treat and once treated become therapy resistant faster.

New point of attack for breast cancer with poor prognosis Scientists from the Friedrich Miescher Institute for Biomedical Research describe how the protein phosphatase SHP2 promotes breast cancer with poor prognosis. As they report Medicine, SHP2 is necessary for the maintenance of the few tumor initiating cells (TICs) in a breast tumor.