Mapping the Role of Vitellogenin in the Inheritance of Stress Response

A mystery of modern biology is how lived experience can be chemically passed to future generations. Although DNA provides the blueprint, the cellular environment, specifically the proteins inherited from the parent, define the context in which those genes are expressed. This non-genetic information transfer suggests that an individual’s fitness is not just a product of their own environment, but a reflection of the stressors faced by their ancestors.

Our lab is specifically investigating vitellogenin (yolk proteins) as a primary vehicle for this inheritance. Yolk proteins are an ideal candidate for transduction factors because they comprise a notable proportion of the embryo’s initial biomass and are synthesized in the parent’s intestine before being loaded into the germline. We hypothesize that external stressors may trigger specific Post-Translational Modifications (PTMs) on these yolk proteins. These chemical tags act as molecular messages, altering the physiological starting state of the embryo. By mapping these modifications, we aim to uncover the logic of how parental experiences are translated into heritable variations in offspring behavior, fitness, and survival.

1.Maintain 7 generations of wild-type (N2), worms under no-stress conditions.

2.Extract protein from embryos of unstressed worms and analyze them using mass-spectrometry.

3.Subject the last generation to three different stresses.

4.Extract protein and analyze using mass-spectrometry.

5.Compare mass-spec data between stressed (treatment) and un-stressed (control) worms to map specific PTMs to unique stresses.

•Track fluorescently tagged vitellogenin proteins in C. elegans to visualize the extent of parental yolk contributions.

•Extract proteins from stressed worms and perform a mass-spectrometry analysis.

•Establish a principled mapping between external conditions and specific PTMs inherited by the next generation.

1.Gallegos, M. (Kimble Lab). (n.d.). Caenorhabditis elegans (Nomarski image). WormClassroom. https://wormclassroom.org/wormclassroom-130/

2.PTMs were extracted from uniport.org and Li et al., “Insulin signaling regulates longevity through protein phosphorylation in Caenorhabditis elegans.” 2021 Nature Communications.

3.Zhai et al.(2022). Immuno-electron microscopy localizez Caenorhabditis elegans vitillogenins along the classic exocytosis route. bioRxiv. https://doi.org/10.1101/2022.06.27.497668

4.C. Tan, T. Wang, H. Park, B. Lomenick, T. Chou, & P.W. Sternberg, Single-tissue proteomics in Caenorhabditis elegans reveals proteins resident in intestinal lysosome-related organelles, Proc. Natl. Acad. Sci. U.S.A. 121 (25) e2322588121, https://doi.org/10.1073/pnas.2322588121 (2024). 

5.Graphics created in  https://BioRender.com