Tran, Tra My et al. (2021) International Worm Meeting "Influences on fat content, fat density and lipid droplets in C. elegans liquid culture"

Schonfelder, Gilbert, Oelgeschlager, Michael, Vogl, Silvia, Wagner, Aline, Menzel, Ralph, Tran, Tra My, Steinberg, Gianna

[International Worm Meeting, 2021]

C. elegans has become an emerging model system to investigate different toxicological endpoints. In particular, fundamental pathways regulating energy homeostasis are highly conserved between C. elegans and humans and thus, the worm provides an important model for the analysis of mechanisms leading to obesity. For example, the analysis of lipid homeostasis as well as fat accumulation in C. elegans can provide important insights into metabolic diseases and the activity of potential obesogenes. In addition, changes in lipid homeostasis by external factors are suspected to be transmitted to subsequent generations. Thus, lipid metabolism might also be a promising read-out in C. elegans to address inter- or transgenerational effects of xenobiotics. In a first step, we studied the influence of different food regimes on worm development, fat content and changes on the level of lipid droplets (LD), the worm's major form of fat storage, to generate "low body fat" or "high body fat" phenotypes. We exposed C. elegans to different OP50 concentrations in liquid culture for three days (L1 to adulthood) and measured worm sizes, triacylglyceride (TAG) contents, LD sizes and density as well as fatty acid (FA) patterns. After three days, worms fed with higher OP50 concentrations showed an increase in body size, higher TAG levels and significant increases in LD size and volume per microm3 in the anterior part of the intestine. Moreover, GC-MS analysis revealed significant differences in FA pattern of adult worms and their eggs, when comparing the "fat" and "lean" phenotypes. Notably, cyclic FA and polyunsaturated fatty acids (PUFA) were affected in a diet-dependent manner. Interestingly, orlistat, an anti-obesogenic drug, could also influence fat density and FA patterns in adult worms as well as eggs. Currently, we are testing effects of (anti-)obesogenes on fat content and FA composition and if those are transmitted to subsequent generations to assess the applicability of these read-outs for the analysis of inter- or transgenerational (adverse) effects.

Shane J Woods et al. (2005) International Worm Meeting "A genome-wide approach to examine genetic robustness through knock-down of duplicate genes using RNAi."

Anthony Rogers, Shane J Woods, David M Rivers, Julie Ahringer

[International Worm Meeting, 2005]

Redundant paralogs have been partially attributed to genetic robustness against null mutations (Gu et al., 2003). In an attempt to assess the genetic robustness of the C. elegans genome we have identified ~ 2000 putative duplicate gene pairs. We have optimized a double RNAi feeding method using our RNAi feeding library (Fraser et al., 2000; Kamath et al., 2003) and an RNAi-supersensitive worm strain to test candidate gene pairs for redundant functions. We will present the data from this screen, where we score embryonic lethality, sterility, and other directly observable phenotypes. This screen presents a resource for novel gene function complementing existing functional genomic screens. In addition, it will allow us to further understand how genomic redundancy is globally organised, as well as the process driving genetic backup. Previous studies of genome redundancy in C. elegans have relied on fitness data from single gene loss-of-function screens (Kamath et al., 2003; Conant & Wagner, 2004). This will be the first genome-wide screen in any higher order organism directly examining genetic robustness on a functional level.