We are a lab studying the molecular mechanisms of epigenetics and how epigenetics impacts a variety of biological processes and diseases
Wash U in St. Louis
Joined June 2019
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Congratulations Jessica, Duygu and the whole team! Looks really cool!
Axolotls use adrenaline signaling to regenerate legs! Today, we can finally share the official publication of a really exciting project we've pursued over the last several years. Thanks to the entire team for their creativity, expertise, and work. cell.com/cell/fulltext/S0092…
This exciting story was spearheaded by Kathleen but she was helped by a number of people some not on twitter including @ArielTelger, @Gautam_Sarkaar, Sharan Surya, @mhafizrothi , @mpmeers, and @simonyuanwang 9/9
Really excited for the next steps of this project to further study whether transgenerational adaptation is universal to different environmental stresses, how conserved this is in other species, and what the precise molecular mechanism is for the transgenerational adaptation. 8/9
A directed screen identified that depletion of the argonautes CSR-1 and HRDE-1 accelerated the transgenerational adaptation (2 generations instead of 4 for no fertility phenotype) and depletion of the H3K27 trimethylase PRC2 complex eliminated the worms ability to adapt 7/9
..is not unique to hypoxia and might be a general phenomena. RNAseq revealed which genes were adapting their expression to repeated generational hypoxia exposure. Most genes still respond to hypoxia treatment but a small subset adapt to repeated generational hypoxia 6/9
We also tested extra glucose which increases neutral lipids and decreases fertility in worms and unexposed descendants. After 2 successive exposures to elevated glucose neutral lipid levels and fertility were the same as unexposed controls.Transgenerational adaptation..5/9
We found that after 2 successive generational exposures to hypoxia, worms were no longer long lived. After 4 successive generational exposures to hypoxia, worms no longer displayed a reduction in fertility. The worms adapted on a transgenerational scale to the repeated stress!4/9
We examined the effects of exposing successive generations to a stress we knew would induce epigenetic inheritance. Hypoxia exposure causes extended lifespan, reduced fertility, and reduced lipids and some of these phenotypes are heritable pubmed.ncbi.nlm.nih.gov/3651… 3/9
Recent work has demonstrated a single exposure to a dramatic stress induces transgenerational phenotypes of altered color, obesity, glucose tolerance, behavior and longevity. But exposed to dif environmental stresses each generation (changes in pesticides and fungicides etc) 2/9
Excited to share our new work on transgenerational adaptation science.org/doi/epdf/10.1126… out today spearheaded by outstanding former undergraduate Kathleen Kim NOT C. elegans adapt to repeated generational stresses and no longer display altered fertility, fat content,+ longevity 1/9
This work was spearheaded by @mhafizrothi, @Gautam_Sarkaar, and Joseph Alhaddad, who were helped by Wayne Mitchell, @KejunYing , Nancy Pohl, Roberto Sotomayor-Mena, Julia Natale, Scarlett Dellacono and @gladyshev_lab . Thanks to all the authors! 8/8
DAF-9 was previously shown by @AntebiLab to produce the signaling lipid dafachronic acid to signal from the germline to the soma to regulate lifespan. pubmed.ncbi.nlm.nih.gov/1174… , pubmed.ncbi.nlm.nih.gov/1736… . dimt-1 induced lifespan extension was dependent on this pathway 7/8
We also found DIMT-1 regulates selective translation of stress resistance and lifespan regulating transcripts in the worm's germline but not in the muscle. One transcript which we identified as displaying differential ribosome occupancy was the cytochrome P450 enzyme DAF-9. 6/8
We found that dimt-1 deficiency requires the TOR signaling pathway and an intact germline to extend lifespan. Using auxin-inducible degron tagged dimt-1 and tissue specific RNAi we found DIMT-1 functions in the worms' germline after mid-life to regulate organismal lifespan 5/8
An RNAi screen identified that dimt-1 KD caused lifespan extension. We had previously shown that DIMT-1 is an 18S rRNA m62A methylase and that methylated rRNAs are transmitted to subsequent generations to drive intergenerational response to starvation pubmed.ncbi.nlm.nih.gov/3768… 4/8