Biology subjects

Fischer, B.

Publications and source records attributed to Fischer, B..

4 recordsLinked to original sources

bioRxiv2018

Understanding RNP remodelling uncovers RBPs functionally required for viral replication

The compendium of RNA-binding proteins (RBPome) has been greatly expanded by the development of RNA-interactome capture (RNA-IC). However, it remains unknown how responsive is the RBPome and whether these responses are biologically relevant. To answer these questions, we created comparative RNA-IC to analyse cells challenged with an RNA virus, called sindbis (SINV). Strikingly, the virus altered the activity of 245 RBPs, many of which were newly discovered by RNA-IC. Mechanistically, alterations in RNA binding upon SINV infection are caused by changes in the subcellular localisation of RBPs and RNA availability. Moreover, RBPome responses are crucial, as perturbation of dynamic RBPs modulates the capacity of the virus to infect the cell. For example, ablation of XRN1 causes cells to be refractory to infection, while GEMIN5 moonlights as a novel antiviral factor. Therefore, RBPome remodelling provides a mechanism by which cells can extensively rewire gene expression in response to physiological cues.\n\nHIGHLIGHTSO_LIA quarter of the RBPome remodels upon SINV infection.\nC_LIO_LIThe remodelling is caused by changes in protein localisation and RNA availability.\nC_LIO_LIRewiring of the RBPome is crucial for viral infection efficacy.\nC_LIO_LIWe discover RBPs with previously unknown anti- or pro-viral activity.\nC_LI

molecular biology↗

bioRxiv2018

Anticipated ITD statistics built-in human sound localization

A neural code adapted to the statistical structure of sensory cues may optimize perception. We investigated whether interaural time difference (ITD) statistics inherent in natural acoustic scenes are parameters determining spatial discriminability. The natural ITD rate of change across azimuth (ITDrc) and ITD variability over time (ITDv) were combined in a Fisher information statistic for assessing the amount of azimuthal information conveyed by this sensory cue. We hypothesized that natural ITD statistics drive the neural code for ITD and thus influence spatial perception. Human spatial discriminability and spatial novelty detection of sounds with invariant statistics correlated with natural ITD statistics. The lack of natural statistics in the stimuli suggests that this correlation results from natural statistics driving the neural code. Additionally, the density distribution of ITD tuning matching natural statistics is consistent with classic models of ITD coding and can explain the ITD tuning distribution observed in the mammalian brainstem. Impact statementHuman brain has incorporated natural statistics of spatial cues to the neural code supporting perception of sound location. Major subject areaNeuroscience; Research organismHuman;

neuroscience↗

bioRxiv2018

Onset of differentiation is posttranscriptionally controlled in adult neural stem cells

The contribution of posttranscriptional regulation of gene expression to neural stem cell differentiation during tissue homeostasis remains elusive. Here we show highly dynamic changes in protein synthesis along differentiation of stem cells to neurons in vivo. Examination of individual transcripts using RiboTag mouse models reveals that neural stem cells efficiently translate abundant transcripts, whereas translation becomes increasingly controlled with the onset of differentiation. Stem cell generation of early neuroblasts involves translational repression of a subset of mRNAs including the stem cell-identity factors Sox2 and Pax6 as well as translation machinery components. In silico motif analysis identifies a pyrimidine-rich motif (PRM) in this repressed subset. A drop in mTORC1 activity at the onset of differentiation selectively blocks translation of PRM-containing transcripts. Our data uncovers how a drop in mTORC1 allows robust simultaneous posttranscriptional repression of key stem cell identity-factors and translation-components and thereby stemness exit and migration.

neuroscience↗

bioRxiv2017

Emphasizing the ‘positive’ in positive reinforcement: Using non-binary rewarding for training monkeys on cognitive tasks

Non-human primates constitute an indispensable model system for studying higher brain functions at the neurophysiological level. They can be trained on highly demanding cognitive tasks, and studies involving these animals elucidated the neuronal mechanisms of various cognitive and executive functions, such as visual attention, working memory, and decision-making. The training of behavioral tasks used to study these processes builds on reinforcement learning and involves many discrete stages. It may takes several months, but frequently lasts a year or longer. The training is usually based on applying a liquid reward as the reinforcer to strengthen the desired behavior, and absence of the reward if the animals response was wrong. We here propose an alternative, non-binary rewarding scheme that aims to minimize unrewarded behavior. We show the potential of this alternative scheme to significantly speed up the training of an animal at various stages, without trade-off in accessible task difficulty or task performance.

animal behavior and cognition↗