Kristopher Schmidt et al. (2007) International Worm Meeting "UNC-53/NAV2 is linked to the Arp 2/3 complex by Abelson kinase interactor."

Jordan Webber, Nancy Marcus, Kristopher Schmidt, Zhongying Zhao, Eve Stringham, David Baillie

[International Worm Meeting, 2007]

UNC-53/NAV2 is required for the guidance and extension of a subset of cells in C.elegans, including the sex muscles, several axons and the excretory canals. UNC-53 protein binds F-actin, and the SH2SH3 adaptor protein SEM-5/GRB2 in vitro, implicating UNC-53 in both signal transduction and actin cytoskeleton dynamics (Stringham et al., 2002, Development 129:3367-3379). Through a yeast two hybrid screen using the first 139 amino acids of UNC-53 inclusive of the calponin homology domain and one LKK motif, we identified B0336.6/ABI-1, the C. elegans homolog to ABI (Abelson tyrosine kinase interactor) as a putative interactor of UNC-53. RNAi feeding experiments directed towards abi-1 using the excretory cell specific marker pgp-12::gfp strain revealed shortened posterior excretory canals, a phenotype also observed in the abi-1(tm494) allele and unc-53 alleles. Truncated posterior canals were also observed in RNAi feeding experiments conducted towards several proteins known to function with abi-1 in actin dynamics in other organisms including: nck-1, wsp-1, wve-1/gex-1 and members of the Arp2/3 complex. Abi-1 RNAi in pmec-4; eri-1(mg366) also revealed truncated PLM axons, a phenotype present in unc-53 mutants. To confirm our yeast two hybrid findings we have additionally shown that UNC-53/NAV2 interacts with ABI-1 by far western overlay. To determine whether UNC-53 colocalizes with ABI-1 we are currently raising antibodies towards ABI-1. In our current model we propose that UNC-53/NAV2, as a large cytoskeleton binding protein with multiple interacting partners, functions to direct cell migration through an actin-mediated process by the Arp2/3 complex.

Webster, Amy K. et al. (2017) International Worm Meeting "Transgenerational effects of long-term dauer arrest."

Hibshman, Jonathan D., Chitrakar, Rojin, Webster, Amy K., Jordan, James M., Baugh, L. Ryan

[International Worm Meeting, 2017]

Long-term effects of extended starvation during L1 arrest have been shown to persist to the F3 generation, suggesting transgenerational epigenetic inheritance. Though effects on lifespan and gene expression have been reported (Rechavi et al), we have only observed relatively subtle transgenerational effects on L1 starvation survival and heat resistance (Jobson, Jordan et al). Furthermore, we found that a minority of starved worms transmitted these effects, requiring phenotype-based sorting of the starved population to detect transgenerational effects among their descendants. In contrast to L1 arrest, larvae can survive dauer arrest for months and the majority of C. elegans in the wild are found as dauers. Persistent effects of dauer arrest have been reported for adults (Hall et al), but transgenerational effects have not been reported. We reasoned that dauer arrest is likely a more ecologically relevant and robust model for transgenerational effects of starvation. Here, we used a liquid culture system carefully controlling worm density and food availability to cause virtually 100% of N2 larvae to enter dauer arrest. These worms remain dauers for months and become reproductive adults when allowed to recover on plates. By assessing various life-history traits, we found that worms subjected to long-term dauer arrest exhibit apparent fitness costs upon recovery, including maternal effects in the F1 generation. However, L1 starvation survival was increased population-wide in the F3 generation (without phenotypic sorting of ancestors), suggesting potentially adaptive transgenerational effects of long-term dauer arrest. This phenotypic effect depended on the length of time the P0 generation spent in dauer arrest, suggesting that dauer formation alone is not sufficient. Notably, the transgenerational effects occurred in the absence of detectable gene expression changes, as if the presumed epigenetic effect on gene expression is distributed over many genes with a small effect on each. This work suggests that experiencing a stress such as starvation can initially be costly, but future generations may exhibit increased fitness in particular circumstances. References: Hall, S.E. et al., A cellular memory of developmental history generates phenotypic diversity in C. elegans. Current Biology, 2010. 20(2): p. 149-155. Jobson, M.A., Jordan J.M. et al., Transgenerational Effects of Early Life Starvation on Growth, Reproduction, and Stress Resistance in Caenorhabditis elegans. Genetics, 2015. 201(1): p. 201-12. Rechavi, O. et al., Starvation-Induced Transgenerational Inheritance of Small RNAs in C. elegans. Cell, 2014. 158(2): p. 277-287.

Pradhan, Sigma et al. (2021) International Worm Meeting "The role of parental diet on progeny's proteome and fitness"

Towbin, Benjamin, Pradhan, Sigma

[International Worm Meeting, 2021]

Animals adjust their phenotype to their environment, which is thought to provide a selective benefit under changing conditions. A famous example of such phenotypic plasticity is the slow down of growth and the delay of aging under dietary restriction (DR). Interestingly, parental DR also affects phenotypes of the F1 generation, for example, DR increases the starvation resistance of progeny (Jordan et al., 2019). Molecularly, DR is associated with a global change in proteome expression, including a reduction in ribosome levels and a proteome-wide slow-down of protein turnover (Dhondt et al., 2016; Visscher et al., 2016). Here, we ask if and how parental diet impacts the proteome of the F1 progeny. We will seek causal relationships between intergenerationally transmitted phenotypes and the inherited proteome. Finally, we aim to determine if the parental control of the proteome provides a selective benefit to their progeny. To address these questions, we have established a tool to precisely quantify ribosomal levels by measuring the luminescence from lysis of HiBit tagged to ribosomal proteins. We plan to globally analyze parental effects on the F1 proteome by proteomics and measure the dynamics of proteome changes, growth rates, and reproduction rates in different nutritional conditions by fluorescence live imaging in microchambers. The project will likely provide important insights about the molecular mechanisms and physiological significance of inter-generational inheritance induced by parental diet.

Hibshman, Jon et al. (2015) International Worm Meeting "Insulin-like signaling and other aging regulators mediate effects of dietary restriction on progeny size and environmental anticipation."

Hibshman, Jon, Baugh, L. Ryan, Hung, Anthony

[International Worm Meeting, 2015]

Dietary restriction delays development, reduces fecundity, and increases lifespan. Here we provide evidence that maternal nutritional status influences provisioning of progeny. In C. elegans, dietary restriction increases progeny size (Harvey and Orbidans, PLOS ONE 2011). We show that progeny of mothers raised under dietary restriction are also buffered against growth-retarding effects of extended L1 arrest (see abstract of J. Jordan et. al.). This suggests that progeny of mothers who experienced limited food are better able to cope with extended starvation. The response to nutrient availability is plastic such that exposure to dietary restriction in late larvae and young adults but not young larvae influences progeny size. Insulin-like signaling plays an important role in regulating embryo size. Disruption of the insulin-like receptor daf-2 in the soma results in larger embryos. Furthermore, mutations in daf-2/InsR and daf-16/FOXO abolish progeny size plasticity in liquid culture-based dietary restriction, with daf-16 epistatic to daf-2. This suggests that insulin-like signaling mediates the effects of dietary restriction on progeny size. We find that skn-1 and pha-4, two canonical regulators of lifespan extension associated with dietary restriction, are also essential for embryo size increase in an eat-2 genetic model of dietary restriction on solid media. These findings reveal that while fecundity is decreased in conditions of limited nutrients, the size and starvation resistance of progeny are increased, suggesting that adults anticipate environmental conditions in progeny provisioning. Furthermore, regulation of progeny size requires some of the same genes and pathways controlling lifespan in response to dietary restriction, implying a common response regulates both aging and progeny provisioning.

Voegtlin, Thomas et al. (2011) International Worm Meeting "An Open-Source Neuromechanical Model of C. Elegans Locomotion."

Cohen, Netta, Voegtlin, Thomas

[International Worm Meeting, 2011]

A neuromechanical model of locomotion in C. elegans was recently proposed by Jordan H. Boyle [1]. One of the main results is that both swimming and crawling can be generated by a single neural circuit, reflexively modulated by the environment. This supports the known experimental results showing that different forms of C. elegans forward locomotion (e.g., swimming and crawling) can be described by a modulation of a single biomechanical gait [2]. The modelling result illustrates the importance and the potential of neuromechanical simulations for the analysis of the worm's behaviour. In order to continue this work, and to make it usable by a broader audience, we have developed a similar neuromechanical model of the worm using CLONES. CLONES (Closed Loop Neural Simulation) is an open source framework for neuromechanical simulations. CLONES implements a communication interface between a neural simulator, called BRIAN [3], and a physics engine for biomedical applications, called SOFA [4]. BRIAN and SOFA are open-source simulators that are easy to use and provide high performance. Our implementation of the worm's locomotion reproduces the neural model described in [1]. However, there are two key differences between the original physical model and our implementation. Firstly, Boyle's model considers that the body of the worm has zero mass (a low Reynolds number approximation). In contrast, the SOFA simulator allows us to integrate equations with mass and inertia. Secondly, the original model uses rigid rods of fixed length orthogonal to the body axis (approximating the incompressibility of the body due to high internal pressure). In SOFA rigid rods are modeled as springs of very high stiffness. The physical system simulated in SOFA is described using a XML syntax. The neural network model interpreted by BRIAN is written in Python, using MATLAB-like syntax. Thus, the model is completely interpreted, and it is possible to visualize/interact with the simulation during runtime. Physical environments containing obstacles or chemical concentration gradients can be defined easily. References 1. Boyle JH: C. elegans locomotion: an integrated approach. PhD thesis, university of Leeds, 2009 2. Berri S, Boyle JH, Tassieri M, Hope IA and Cohen N, Forward locomotion of the nematode C. elegans is achieved through modulation of a single gait HFSP J 3:186, 2009; 3. Goodman DF, Brette R: Brian: a simulator for spiking neural networks in Python. Front Neuroinform 2:5, 2008 4. Allard J, Cotin S, Faure F, Bensoussan PJ, Poyer F, Duriez C, Delingette H, Grisoni L: SOFA - an Open Source Framework for Medical Simulation. Medicine Meets Virtual Reality (MMVR'15), pp. 13-18, 2007.