Sifoglu, Deniz et al. (2021) International Worm Meeting "Neuropeptide modulation of insulin signaling in bacteria-dependent survival"

Maier, Wolfgang, Alcedo, Joy, Sifoglu, Deniz

[International Worm Meeting, 2021]

Bacterial food sources will differentially affect C. elegans physiology and survival. For example, C. elegans fed two E. coli strains-the B type OP50 versus the K12 type CS180-exhibit different survival phenotypes. Wild-type C. elegans fed OP50 have a higher rate of early deaths compared to C. elegans fed CS180. The early deaths on OP50 are characterized by swollen pharynges (P-deaths) that resulted from bacterial accumulation within the tissue. In contrast, worms fed CS180 are more resistant to P-deaths. We find that the neuropeptide neuromedin U receptor nmur-1 inhibits P-deaths on OP50, but not on CS180. Interestingly, however, nmur-1 promotes the opposite response when the insulin receptor daf-2 has reduced activity-where nmur-1 now promotes P-deaths on OP50. Since both effects of nmur-1 appear dependent on the FOXO daf-16 transcription factor, we propose that nmur-1 acts as a modulator of insulin signaling. Thus, NMUR-1 ensures that the insulin receptor DAF-2 signals at the appropriate level to promote pharyngeal health and optimal survival in response to specific bacteria.

Sifoglu, Deniz et al. (2015) International Worm Meeting "The Role of Neuropeptide Neuromedin U Signaling in the Sensory Influence on C. elegans Physiology via Food-Type Recognition."

Mishra, Shashwat, Neagu, Anca, Alcedo, Joy, Gatsi, Roxani, Sifoglu, Deniz, Maier, Wolfgang

[International Worm Meeting, 2015]

Sensory perception of various environmental cues can affect physiology. For example, olfactory and gustatory sensory systems can either have lengthening or shortening effects on the lifespan of C. elegans. The sensory influence on lifespan via food-type recognition can be mediated by nmur-1, which is the C. elegans homolog of mammalian neuromedin U receptors. Indeed, nmur-1 has been shown to inhibit longevity in a food type-dependent manner. nmur-1 also affects the feeding and developmental rates of C. elegans on different food types, although these nmur-1 effects are independent from the nmur-1 effect on longevity. Currently, we are conducting cell-specific rescues of the nmur-1 mutation to delineate a food-sensing circuit through which NMUR-1 regulates longevity in response to different food-derived cues.

Sifoglu, Deniz et al. (2017) International Worm Meeting "The putative actin-binding and scaffold protein filamin-2 affects C. elegans survival in response to different bacterial food sources."

Maier, Wolfgang, Husain, Zahabiya, Sifoglu, Deniz, Alcedo, Joy, Regenass, Martin

[International Worm Meeting, 2017]

Animal survival can be affected by either food levels or food composition, where the effects can be mediated by the perception and/or metabolism of macro- and micro-nutrients. Indeed, different bacterial food sources have distinct effects on the physiology and survival of the nematode C. elegans, presumably by changing certain gene activities within the animal. Recently, we have found that the predicted actin-binding and scaffold protein, filamin-2, shortens C. elegans lifespan on some bacteria, but not on other bacteria. The bacterial food source may serve not only as a source of nutrients and metabolites, but also as cues that elicit the animal's innate immune responses. However, the effects of filamin-2 do not appear to be part of a general innate immune response. We find that filamin-2 mutants show increased survival on some pathogenic bacteria, but not on other bacteria that confers a higher degree of pathogenicity in C. elegans. Thus, filamin-2 likely regulates the animal's response to specific bacteria-derived cues. At present, we are elucidating the molecular and cellular mechanism(s) through which filamin-2 affects survival in a bacteria-specific manner.