Biology subjects

Apfeld, J.

Publications and source records attributed to Apfeld, J..

8 recordsLinked to original sources

bioRxiv2026

The C. elegans nervous system reads the internal state of the hydrogen peroxide-detoxification machinery to trigger escape from this common reactive chemical

Hydrogen peroxide (H2O2) is the most common reactive chemical threat faced by organisms. Here, we map the neural circuit that drives chemotactic escape from environmental H2O2 in the nematode C. elegans. Twenty-four neuron classes with sensory endings at the mouth and nose of the animal detect H2O2. Their response dynamics encode stimulus intensity and exposure history, and their partial redundancy makes avoidance resilient to the loss of individual inputs. Sensing begins when H2O2 oxidizes the peroxidatic and resolving cysteines of the cytosolic peroxiredoxin PRDX-2, which relays this oxidative signal to cysteines on the LITE-1 and GUR-3 ion channels, triggering calcium influx in sensory neurons that drive escape. Most of these neurons release glutamate to drive H2O2-dependent excitation of AIA interneurons, whereas others signal through non-glutamatergic routes, providing multiple routes for signal transmission. Thus, the C. elegans nervous system acts as a hydrogen peroxide sentinel that monitors H2O2-induced changes in the intracellular H2O2-detoxification machinery and relays them to interneurons driving organism-wide escape. This raises the possibility that circuit defects in aging and neurodegenerative disease arise from altered peroxiredoxin-mediated H2O2 signaling rather than primarily from direct macromolecular damage.

neuroscience↗

bioRxiv2025

Wormtrails: a python package for viewing C. elegans movement

Wormtrails is a python package designed to create images and videos depicting the motion of C. elegans on solid media. Darkfield or brightfield images may be converted into stills or movies, with time encoded by color. This package was primarily designed to be used for visualizing locomotion during chemotaxis, but it may be used to visualize locomotory patterns in a wide array of behavioral assays.

neuroscience↗

bioRxiv2022

Neuronal temperature perception induces specific defenses that enable C. elegans to cope with the enhanced reactivity of hydrogen peroxide at high temperature

Hydrogen peroxide is the most common reactive chemical that organisms face on the microbial battlefield. The rate with which hydrogen peroxide damages biomolecules required for life increases with temperature, yet little is known about how organisms cope with this temperature-dependent threat. Here, we show that Caenorhabditis elegans nematodes use temperature information perceived by sensory neurons to cope with the temperature-dependent threat of hydrogen peroxide produced by the pathogenic bacterium Enterococcus faecium. These nematodes preemptively induce the expression of specific hydrogen peroxide defenses in response to perception of high temperature by a pair of sensory neurons. These neurons communicate temperature information to target tissues expressing those defenses via an insulin/IGF1 hormone. This strategy, which we call "enhancer sensing," is the first example of a multicellular organism inducing their defenses to a chemical when they sense an inherent enhancer of the reactivity of that chemical.

neuroscience↗

bioRxiv2021

Modulation of sensory perception by hydrogen peroxide enables Caenorhabditis elegans to find a niche that provides both food and protection from hydrogen peroxide

Hydrogen peroxide (H2O2) is the most common chemical threat that organisms face. Here, we show that H2O2 alters the bacterial food preference of Caenorhabditis elegans, enabling the nematodes to find a safe environment with food. H2O2 induces the nematodes to leave food patches of laboratory and microbiome bacteria when those bacterial communities have insufficient H2O2-degrading capacity. The nematodes behavior is directed by H2O2-sensing neurons that promote escape from H2O2 and by bacteria-sensing neurons that promote attraction to bacteria. However, the input for H2O2-sensing neurons is removed by bacterial H2O2-degrading enzymes and the bacteria-sensing neurons perception of bacteria is prevented by H2O2. The resulting cross-attenuation provides a general mechanism that ensures the nematodes behavior is faithful to the lethal threat of hydrogen peroxide, increasing the nematodes chances of finding a niche that provides both food and protection from hydrogen peroxide.

neuroscience↗

bioRxiv2020

The heat shock transcription factor HSF-1 protects Caenorhabditis elegans from peroxide stress

Cells induce conserved defense mechanisms that protect them from oxidative stress. How these defenses are regulated in multicellular organisms is incompletely understood. Using the nematode Caenorhabditis elegans, we show that the heat shock transcription factor HSF-1 protects the nematode from the oxidative stress induced by environmental peroxide. In response to a heat shock or a mild temperature increase, HSF-1 protects the nematodes from subsequent oxidative stress in a manner that depends on HSF-1s transactivation domain. At constant temperature, HSF-1 protects the nematodes from oxidative stress independently of its transactivation domain, likely by inducing the expression of asp-4/cathepsin D and dapk-1/dapk. Thus, two distinct HSF-1-dependent processes protect C. elegans from oxidative stress.

genetics↗

bioRxiv2020

C. elegans processes sensory information to choose between freeloading and self-defense strategies

Hydrogen peroxide is the preeminent chemical weapon that organisms use for combat. Individual cells rely on conserved defenses to prevent and repair peroxide-induced damage, but whether similar defenses might be coordinated across cells in animals remains poorly understood. Here, we identify a neuronal circuit in the nematode Caenorhabditis elegans that processes information perceived by two sensory neurons to control the induction of hydrogen-peroxide defenses in the organism. We found that catalases produced by Escherichia coli, the nematodes food source, can deplete hydrogen peroxide from the local environment and thereby protect the nematodes. In the presence of E. coli, the nematodes neurons signal via TGF{beta}-insulin/IGF1 relay to target tissues to repress expression of catalases and other hydrogen-peroxide defenses. This adaptive strategy is the first example of a multicellular organism modulating its defenses when it expects to freeload from the protection provided by molecularly orthologous defenses from another species.

neuroscience↗

bioRxiv2020

The SensorOverlord predicts the accuracy of measurements with ratiometric biosensors

Two-state ratiometric biosensors change conformation and spectral properties in response to specific biochemical inputs. Much effort over the past two decades has been devoted to engineering biosensors specific for ions, nucleotides, amino acids, and biochemical potentials. The utility of these biosensors is diminished by empirical errors in fluorescence-ratio signal measurement, which reduce the range of input values biosensors can measure accurately. Here, we present a formal framework and a web-based tool, the SensorOverlord, that predicts the input range of two-state ratiometric biosensors given the experimental error in measuring their signal. We demonstrate the utility of this tool by predicting the range of values that can be measured accurately by biosensors that detect pH, NAD+, NADH, NADPH, histidine, and glutathione redox potential. The SensorOverlord enables users to compare the predicted accuracy of biochemical measurements made with different biosensors, and subsequently select biosensors that are best suited for their experimental needs.

cell biology↗

bioRxiv2017

Age-dependence and aging-dependence: The case of neuronal loss and lifespan in a C. elegans model of Parkinson’s disease

It is often assumed, but not established, that the major neurodegenerative diseases, such as Parkinsons disease, are not just age-dependent (their incidence changes with time) but actually aging-dependent (their incidence is coupled to the process that determines lifespan). To determine a dependence on the aging process requires the joint probability distribution of disease onset and lifespan. For human Parkinsons disease, such a joint distribution is not available because the disease cuts lifespan short. To acquire a joint distribution, we resorted to an established C. elegans model of Parkinsons disease in which the loss of dopaminergic neurons is not fatal. We find that lifespan is not correlated with the loss of neurons and that a lifespan-extending intervention into insulin/IGF1 signaling accelerates neuronal loss, while leaving death and neuronal loss times uncorrelated. This suggests that distinct and compartmentalized instances of the same genetically encoded insulin/IGF1 signaling machinery act independently to control neurodegeneration and lifespan in C. elegans. Although the human context might well be different, our study calls attention to maintaining a rigorous distinction between age-dependence and aging-dependence.

developmental biology↗