Biology subjects

Peter, E.

Publications and source records attributed to Peter, E..

6 recordsLinked to original sources

bioRxiv2026

Sexually antagonistic environments and the stability of environmental sex determination

Just as sexually antagonistic genetic variants have different effects on male and female fitness, environmental conditions too can have sexually antagonistic fitness effects. Such Charnov-Bull effects have been invoked to explain the origin and persistence of environmental sex determination (ESD), which allows development of each sex in the environments in which it has a comparative advantage. Here, we study different forms of Charnov-Bull effects to characterize how they shape the evolution and stability of ESD. We show that the precise functional form of Charnov-Bull effects can generate large differences in the vulnerability of ESD systems to the invasion of sex-biasing alleles, as well as in the fate of those alleles if they invade. For some configurations of Charnov-Bull effects, strong sex-biasing alleles are likely to spread to intermediate frequencies, rather than to fixation, resulting in mixed ESD systems in which large genetic effects segregate. Overall, our results indicate that the precise nature of Charnov-Bull effects can play a crucial role in the evolutionary dynamics of ESD.

evolutionary biology↗

bioRxiv2024

PTX3 Governs Fibroblast-Epithelial Dynamics in Lung Injury and Repair

Dysfunctional interactions between fibroblasts and epithelial cells contribute to the progression of chronic lung diseases, including idiopathic pulmonary fibrosis (IPF). In this study, we utilized a coculture model of human small airway epithelial cells and fibroblasts to investigate intercellular communication during disease progression. Our transcriptomic and proteomic profiling reveal that fibroblasts repair epithelial cells in acute injury by boosting epithelial fatty acid metabolism; conversely, they exacerbate epithelial damage in chronic injury scenarios. By delineating regulators involved in these responses, we identified pentraxin 3 (PTX3) as a key antifibrotic factor secreted by fibroblasts in response to acute epithelial injury. Importantly, PTX3 levels are decreased in bronchoalveolar lavage (BAL) samples from IPF patients compared to non-fibrotic controls, indicating a potential link between diminished PTX3 levels and fibrosis progression. Furthermore, adding PTX3 to chronically injured epithelial-fibroblast cocultures mitigated the pro-fibrotic response and restored the epithelial barrier integrity. These findings highlight the dual roles of fibroblasts and the critical function of PTX3 in lung injury and repair, offering insights for therapeutic strategies.

molecular biology↗

bioRxiv2022

WiChR, a highly potassium selective channelrhodopsin for low-light two-photon neuronal inhibition

The electric excitability of muscle, heart and brain tissue relies on the precise interplay of Na+- and K+-selective ion channels. The involved ion fluxes are controlled in optogenetic studies using light-gated channelrhodopsins (ChRs). While non-selective cation-conducting ChRs are well-established for excitation, K+-selective ChRs (KCRs) for efficient inhibition have only recently come into reach. Here, we report the molecular analysis of recently discovered KCRs from the stramenopile Hyphochytrium catenoides and identify a novel type of hydrophobic K+-selectivity filter. Next, we demonstrate that the KCR signature motif is conserved in related stramenopile ChRs. Among them, WiChR from Wobblia lunata features an unmatched 80-fold preference for K+ over Na+, stable photocurrents under continuous illumination and a prolonged open state lifetime. Well expressed in neurons, WiChR allows two-photon inhibition at low irradiance and reduced tissue heating,_recommending WiChR as the long-awaited efficient and versatile optogenetic inhibitor.

neuroscience↗

bioRxiv2020

The effect of salt on the dynamics of CoV-2 RBD at ACE2

In this article, we investigate the effect of electrolytes on the stability of the complex between the coronavirus type 2 spike protein receptor domain (CoV-2 RBD) and ACE2, which plays an important role in the activation cascade at the viral entry of CoV-2 into human cells. At the cellular surface, electrolytes play an important role, especially in the interaction of proteins near the membrane surface. Additionally, the binding interface of the CoV-2 RBD - ACE2 complex is highly hydrophilic. We simulated the CoV-2 RBD - ACE2 complex at varying salt concentrations over the concentration range from 0.03 M to 0.3 M of calcium and sodium chloride over an individual simulation length of 750 ns in 9 independent simulations (6.75 {micro}s total). We observe that the CoV-2 RBD - ACE2 complex is stabilized independent of the salt concentration. We identify a strong negative electrostatic potential at the N-terminal part of CoV-2 RBD and we find that CoV-2 RBD binds even stronger at higher salt concentrations. We observe that the dynamics of the N-terminal part of CoV-2 RBD stabilize the protein complex leading to strong collective motions and a stable interface between CoV-2 RBD and ACE2. We state that the sequence of CoV-2 RBD might be optimized for a strong binding to ACE2 at varying salt concentrations at the cellular surface, which acts as a key component in the activation of CoV-2 for its viral entry. SIGNIFICANCEA novel coronavirus, coronavirus type 2 (CoV-2), was identified as primary cause for a worldwide pandemic of the severe acute respiratory syndrome (SARS CoV-2). The CoV-2 spike protein is a major target for the development of a vaccine and potential strategies to inhibit the viral entry into human cells. At the cellular surface, CoV-2 activation involves the direct interaction between ACE2 and CoV-2 RBD. At the cellular surface, electrolytes play an important role, especially in the interaction of proteins near the membrane surface. We thus investigate the effect of ion conditions on the interaction of the CoV-2 RBD - ACE2 complex and find stabilizing effects. We speculate that CoV-2 RBD is optimized for strong binding to ACE2 at varying salt concentrations.

biophysics↗

bioRxiv2020

Inhibition of Corona virus spike protein binding to ACE2

In this paper, we investigate the molecular assembly processes of a Coronavirus Spike protein fragment, the hexapeptide YKYRYL on the ACE2 receptor and its inhibitory effect on the aggregation and activation of the CoV-2 spike receptor protein at the same receptor protein. In agreement with an experimental study, we find a high affinity of the hexapeptide to the binding interface between the spike receptor protein and ACE2, which we investigate using 20 independent equilibrium MD simulations over a total of 1 s and a 200 ns enhanced MD simulation. We then evaluate the effect of the hexapeptide on the aggregation process of the spike receptor protein to ACE2 in long-time enhanced MD simulations. In that set of simulations, we find that the spike receptor protein does not bind to ACE2 with the binding motif shown in experiments, but it rotates due to an electrostatic repulsion and forms a hydrophobic interface with ACE2. Surprisingly, we observe that the hexapeptide binds to the spike receptor domain, which has the effect that this protein only weakly attaches to ACE2, so that the activation of the spike protein receptor might be inhibited in this case. Our results indicate that the hexapeptide might be a possible treatment option which prevents the viral activation through the inhibition of the interaction between ACE2 and the spike receptor protein. SIGNIFICANCEA novel coronavirus, CoV-19 and a later phenotype CoV-2 were identified as primary cause for a severe acute respiratory syndrome (SARS CoV-2). The spike (S) protein of CoV-2 is one target for the development of a vaccine to prevent the viral entry into human cells. The inhibition of the direct interaction between ACE2 and the S-protein could provides a suitable strategy to prevent the membrane fusion of CoV-2 and the viral entry into human cells. Using MD simulations, we investigate the assembly process of a Coronavirus Spike protein fragment, the hexapeptide YKYRYL on the ACE2 receptor and its inhibitzory effect on the aggregation and activation of the CoV-2 spike receptor protein at the same receptor protein.

biophysics↗

bioRxiv2019

MerMAIDs: A novel family of metagenomically discovered, marine, anion-conducting and intensely desensitizing channelrhodopsins.

Channelrhodopsins (ChRs) are algal light-gated ion channels widely used as optogenetic tools for manipulating neuronal activity. ChRs desensitize under continuous bright-light illumination, resulting in a significant decline of photocurrents. We describe a novel, metagenomically identified family of phylogenetically distinct anion-conducting ChRs (designated MerMAIDs). MerMAIDs almost completely desensitize during continuous illumination due to accumulation of a late non-conducting photointermediate that disrupts the ion permeation pathway. MerMAID desensitization can be fully explained by a single photocycle in which a long-lived desensitized state follows the short-lived conducting state. A conserved cysteine is the critical factor in desensitization, as its mutation results in recovery of large stationary photocurrents. The rapid desensitization of MerMAIDs enables their use as optogenetic silencers for transient suppression of individual action potentials without affecting subsequent spiking during continuous illumination. Our results could facilitate the development of further novel optogenetic tools from metagenomic databases and enhance general understanding of ChR function.

biophysics↗