Lanza, Enrico et al. (2021) International Worm Meeting "C. elegans-based chemosensation strategy for the early detection of cancer metabolites in urine samples"

Folli, Viola, Ferrarese, Giuseppe, Caprini, Davide, Lonardo, Maria Teresa, Pannone, Luca, Ruocco, Giancarlo, Di Rocco, Martina, Martinelli, Simone, Schwartz, Silvia, Milanetti, Edoardo, Lanza, Enrico

[International Worm Meeting, 2021]

Olfaction is one of the primary mechanisms through which many animals adapt to environmental changes. Olfactory receptors, which in all animals belong to the G-protein coupled receptors (GPCRs) family, play a crucial role in distinguishing the wide range of volatile or soluble molecules by directly binding them with high accuracy. Chemosensation is particularly developed in organisms lacking long-range sensory mechanisms like hearing and vision. The genome of the nematode Caenorhabditis elegans possesses a remarkable number of genes encoding chemosensory receptors, making it able to detect a similar number of odorants as mammals, despite the extremely low number of chemosensory neurons available. Here, we show that C. elegans displays attraction towards urine samples collected from women with breast cancer but avoids those from healthy subjects. This behavior is strongly influenced by the female hormone cycle. Behavioral assays performed on animals in which the AWC sensory neurons were genetically ablated demonstrate an essential role of these neurons in sensing cancer odorants. Calcium imaging experiments on AWC neurons dramatically increase the accuracy in discriminating between positive and control samples (with an accuracy of 97.22%). Also, chemotaxis assays performed on mutant animals harboring individual deletion in genes encoding GPCRs expressed in AWC neurons allow us to identify candidate receptors that are likely to be involved in binding cancer metabolites. This finding suggests that a specific alteration of a restricted number of metabolites is sufficient for the highly accurate cancer discriminating behavior of C. elegans, which may allow in principle to identify the fundamental fingerprint of breast cancer.

Caprini, Davide et al. (2021) International Worm Meeting "The C.elegans AWCON olfactory neuron responds to tangential component of mechanical stimuli and its activation is mediated by TAX-4 cGMP-gated cation channel"

Nicoletti, Martina, Ferrarese, Giuseppe, Lanza, Enrico, Caprini, Davide, Chiodo, Letizia, Folli, Viola, Schwartz, Silvia, Lucente, Valeria, Milanetti, Edoardo

[International Worm Meeting, 2021]

The two major sensory modalities of C.elegans are chemosensation and mechanosensation. Calcium imaging experiments have previously suggested that these two modalities are functionally segregated. Here, we demonstrate that AWCON olfactory neuron, which plays a crucial role in chemosensation, does not only respond to chemicals but also to mechanical stimuli. Touch senses mechanical stimuli, comprising two components: pressure and shear stress. Previous studies assessing mechanosensation in C.elegans have always referred to pressure stimuli only. In this work, we shown that C.elegans senses also the tangential component of mechanical stimuli by recruiting the AWC neuron, and we give evidence that this ability may depend on specific odor receptors. We further show that the mechanosensitivity of AWC neurons has an intrinsic nature rather than a synaptic origin and the calcium transient response is mediated by TAX-4 cGMP-gated cation channel, suggesting the involvement of one or more "odorant" receptors in AWC mechano-transduction. Moreover, calcium events show a bistable neuronal regime structurally different from the typical calcium response to a chemical stimulus. The observed bistability indicates that AWCON adopts distinct sensory strategies for chemo-and mechanosensation, adapting molecules and receptors to convert chemical and mechanical stimuli into different cellular signaling.

Julia Samann et al. (2006) European Worm Meeting "Using C. elegans to Model the Systems Biology of Stress Response and Age-Related Disorders"

Julia Samann, Enrico Schmidt, Ralf Baumeister, Mark Seifert

[European Worm Meeting, 2006]

Julia Smann, Enrico Schmidt, Mark Seifert and Ralf Baumeister. Our lab is interested in understanding the connection of stress response and disease. According to a prevailing theory, aging is characterized by the declining activity of genome maintenance and repair mechanisms that deal with the detrimental consequences of external and internal stress. This eventually results in the accumulation of DNA mutations and increases the risk of stroke, cancer, coronary heart diseases, and degenerative disorders (the four major causes of death in our society). One focus of our research is the generation of C. elegans model to study the biological role of the affected genes. We focus here on genes whose mutations segregate with hereditary cases of Parkinsons Disease to result in an early age-of-onset and rapid progression. C. elegans homologues of four respective genes were identified and mutants are available. These are the ubiquitin ligase parkin/pdr-1, the mitochondrial kinase PINK1/pink-1, two genes with strong similarities to human DJ-1 (pdr-2 and pdr-3: Parkinsons Disease-related gene 2 and 3), and the cGMP binding protein Dardarin/LRRK2/lrk-1. All of them have been linked to intracellular mechanisms of (oxidative and unfolded protein) stress response, suggesting that they can be functionally linked to one another. We have initiated genome-wide screens to characterize the Parkinome, the interaction network of factors related to Parkinsons Disease. One purpose of this endeavour is the identifation of common targets and regulators of PD-related gene products, as well as the modeling of their roles in the onset of disease. Using the split-ubiquitin yeast two-hybrid interaction screen, we identified over 100 proteins as potential interactors for PD-related proteins. Using a medium throughput biochemical assay we are currently working on the confirmation of these interactions, and apply genetic and pharmacological assays to understand the physiological processes that are perturbed in mutants. In previous experiments, we generated screening models for parkin and human ?-synuclein mutants in C. elegans. The expression of ?-synuclein A53T in a pdr-1 mutant background that behaves similar as the Parkin mutants found in PD resulted in temperature-sensitive toxicity that enabled us to screen for suppressors/enhancers of this phenotype. Until now, we identified more than 50 modulators of this toxicity. Results of the various screens support the model of a functional connection between PD-related factors.