Biology subjects

Kopp, F.

Publications and source records attributed to Kopp, F..

5 recordsLinked to original sources

bioRxiv2026

A cilia-dependent inflammatory programme links bacterial detection to kidney disease

The primary cilium is a microtubule-based sensory organelle projecting from the plasma membrane of most mammalian cells. Genetic defects in ciliary components cause chronic kidney disease (CKD) characterized by heightened production of inflammatory and fibrogenic mediators by tubular epithelial cells. Yet, whether this reflects a physiological role of the primary cilium remains unknown. Here, we show that primary cilia on kidney tubular cells bind uropathogenic Escherichia coli and, in response to bacterial components, initiate a fibro-inflammatory program reminiscent of CKD. Integrating single-cell transcriptomics with conditional mouse models, we observed that epithelial cilia orchestrate a similar fibro-inflammatory response in the absence of infection during CKD. This convergence reveals a shared cilia-dependent signalling axis governing both host-pathogen responses and CKD progression. Mechanistically, cilia ablation selectively impairs tubular responses to ADP-heptose, a pathogen-associated molecular pattern that activates NF-{kappa}B via the cytosolic innate immune receptor ALPK1. In human kidney organoids, ADP-heptose induces robust fibro-inflammation, and genetic or pharmacological inhibition of ALPK1 attenuates this response in a rodent CKD model. Together, these findings identify primary cilia as central orchestrators of a fibro-inflammatory program linking pathogen detection to kidney disease progression.

physiology↗

bioRxiv2019

PUMILIO, but not RBMX, binding is required for regulation of genomic stability by noncoding RNA NORAD

NORAD is a highly-conserved and abundant long noncoding RNA (lncRNA) that is required for maintenance of genomic stability in mammals. Although initial characterization of NORAD established it as a negative regulator of PUMILIO (PUM) proteins in the cytoplasm, a nuclear role for NORAD in genome maintenance through an interaction with the RNA binding protein RBMX has also been reported. Here we addressed the relative contributions of NORAD:PUM and NORAD:RBMX interactions to the regulation of genomic stability by this lncRNA. Extensive RNA FISH and fractionation experiments established that NORAD localizes predominantly to the cytoplasm with or without DNA damage. Moreover, genetic rescue experiments demonstrated that PUM binding is required for maintenance of genomic stability by NORAD whereas binding of RBMX is dispensable for this function. These data therefore establish an essential role for the NORAD:PUM interaction in genome maintenance and provide a foundation for further mechanistic dissection of this pathway.

molecular biology↗

bioRxiv2018

PUMILIO hyperactivity drives premature aging of Norad-deficient mice

Although numerous long noncoding RNAs (lncRNAs) have been identified, our understanding of their roles in mammalian physiology remains limited. Here we investigated the physiologic function of the conserved lncRNA Norad in vivo. Deletion of Norad in mice results in genomic instability and mitochondrial dysfunction, leading to a dramatic multi-system degenerative phenotype resembling premature aging. Loss of tissue homeostasis in Norad-deficient animals is attributable to augmented activity of PUMILIO proteins, which act as post-transcriptional repressors of target mRNAs to which they bind. Norad is the preferred RNA target of PUMILIO2 (PUM2) in mouse tissues and, upon loss of Norad, PUM2 hyperactively represses key genes required for mitosis and mitochondrial function. Remarkably, enforced Pum2 expression fully phenocopies Norad deletion, resulting in rapid-onset aging-associated phenotypes. These findings provide new insights and open new lines of investigation into the roles of noncoding RNAs and RNA binding proteins in normal physiology and aging.

molecular biology↗

bioRxiv2017

10-Month-Old Infants Are Sensitive To The Time Course Of Perceived Actions: Evidence From A Study Combining Eye-tracking And EEG

Research has shown that infants are able to track a moving target efficiently - even if it is transiently occluded from sight. This basic ability allows prediction of when and where events happen in everyday life. Yet, it is unclear whether, and how, infants internally represent the time course of ongoing movements to derive predictions. In this study, 10-month-old crawlers observed the video of a same-aged crawling baby that was transiently occluded and reappeared in either a temporally continuous or non-continuous manner (i.e., delayed by 500 ms vs. forwarded by 500 ms relative to the real-time movement). Eye movement and rhythmic neural brain activity (EEG) were measured simultaneously. Eye movement analyses showed that infants were sensitive to slight temporal shifts in movement continuation after occlusion. Furthermore, brain activity related to sensorimotor rather than mnemonic processing differed between observation of continuous and non-continuous movements. Early sensitivity to an actions timing may hence be explained within the internal real-time simulation account of action observation. Overall, the results support the hypothesis that 10-month-old infants are well prepared for internal representation of the time course of observed movements that are within the infants current motor repertoire.

neuroscience↗

bioRxiv2017

Visual Context Modulates Action Perception In 10-Month-Old Infants

Research on early action perception has documented infants astounding abilities in tracking, predicting, and understanding other peoples actions. Common interpretations of previous findings tend to generalize across a wide range of action stimuli and contexts. In this study, ten-month-old infants repeatedly watched a video of a same-aged crawling baby that was transiently occluded. The video was presented in alternation with videos displaying visually either dissimilar movements (i.e., distorted human, continuous object, and distorted object movements) or similar movements (i.e., delayed or forwarded versions of the crawling video). Eye-tracking behavior and rhythmic neural activity, reflecting attention (posterior alpha), memory (frontal theta), and sensorimotor simulation (central alpha), were concurrently assessed. Results indicate that, when the very same movement was presented in a dissimilar context, it was tracked at more rear parts of the target and posterior alpha activity was elevated, suggesting higher demands on attention-controlled information processing. We conclude that early action perception is not immutable but shaped by the immediate visual context in which it appears, presumably reflecting infants ability to flexibly adjust stimulus processing to situational affordances.

neuroscience↗