- B.S. University of Wyoming, 1999
- PhD, University of Utah, 2006
Germ cells are the progenitors of reproductive cells, and the only cells in sexually reproducing animals that have the potential to give rise to all of the cell types of each subsequent generation. In our lab, we want to understand how these totipotent and immortal properties are conferred. Part of the answer comes from special aggregates called “germ granules” that are found just outside the nucleus of germ cells. Recent research has shown that germ granules play a critical role in maintaining the totipotent and immortal properties of the germline. Take away an organism’s germ granules and it will become sterile. In some organisms, introducing germ granules in cells outside of the germline will restore cellular immortality and totipotency, and will reprogram them into germline stem cells.
Germ granules are conserved in their appearance, subcellular localization, and composition from worms to humans. Because of this, we are able to quickly ascertain the mechanisms by which germ granules function by studying them in a small roundworm called C. elegans. This well-established model organism is responsible for much of what we know about developmental genetics in humans. Using fluorescence microscopy, germ granules (called P granules in C. elegans) can be observed in the germ line of transparent worms at all stages of development. The genetic power of C. elegans combined with its short 3-day generation time and transparency offers an opportunity to study the function of germ granules that isn’t feasible in more complex model organisms.
A focus of our research is to understand the biophysical properties of germ granules, how they are assembled, and the components that affect their subcellular distribution. We have shown that germ granules are held together by weak hydrophobic interactions, and that they extend the size exclusion barrier of the nuclear pore complex out into the cytoplasm of germ cells. Here germ granules create a specialized microenvironment that facilitates post-transcriptional processing events that are exclusive to the germline. We are continuing to investigate the specifics of those processing events to understand how they are used to maintain the pluripotent and immortal properties of germ cells, and how these mechanisms can be applied to unlocking stem cell-like properties in other cell types.
How do stem cells maintain pluripotency — the capacity to become other cell types in the body? Can our ability to regenerate after disease or injury be improved with the ability to switch on and off cellular pluripotency?
To answer these and other questions, the Updike Lab derives cues from quintessential stem cells found in the germline. Germline stem cells (GSCs) are the precursors to oocytes and sperm, and these cells must retain their stem cell attributes so fertilized embryos can give rise to all of the cell types of each subsequent generation.
To achieve this immortal potential, germ cells survey gene expression activity through unique structures called germ granules in the cell’s cytoplasm. Germ granules use small RNA machinery to read cellular messages and determine whether they are licensed for expression, shutting down aberrant messages whose expression could result in the loss of pluripotency. While germ granules are specific to the germline, they are found in animals, from worms to humans. The Updike Lab studies germ-granule function in C. elegans nematodes, where they are readily accessible and visible at all stages of development. This work will impact our understanding of germ-granule function and human fertility and the role of the cell’s cytoplasm in wound healing, regeneration, and tumorigenesis.
- Rochester JD, Min H, Gajjar GA, Sharp CS, Maki NJ, Rollins JA, Keiper BD, Graber JH, Updike DL. GLH-1/Vasa represses neuropeptide expression and drives spermiogenesis in the C. elegans germline. Dev Biol. 2022 Dec;492:200-211. doi: 10.1016/j.ydbio.2022.10.003. Epub 2022 Oct 21. PubMed PMID: 36273621; PubMed Central PMCID: PMC9677334.
- Spaulding EL, Feidler AM, Cook LA, Updike DL. RG/RGG repeats in the C. elegans homologs of Nucleolin and GAR1 contribute to sub-nucleolar phase separation. Nat Commun. 2022 Nov 3;13(1):6585. doi: 10.1038/s41467-022-34225-5. PubMed PMID: 36329008; PubMed Central PMCID: PMC9633708.
- Marnik EA, Almeida MV, Cipriani PG, Chung G, Caspani E, Karaulanov E, Gan HH, Zinno J, Isolehto IJ, Kielisch F, Butter F, Sharp CS, Flanagan RM, Bonnet FX, Piano F, Ketting RF, Gunsalus KC, Updike DL. The Caenorhabditis elegans TDRD5/7-like protein, LOTR-1, interacts with the helicase ZNFX-1 to balance epigenetic signals in the germline. PLoS Genet. 2022 Jun;18(6):e1010245. doi: 10.1371/journal.pgen.1010245. eCollection 2022 Jun. PubMed PMID: 35657999; PubMed Central PMCID: PMC9200344.
- Phillips CM, Updike DL. Germ granules and gene regulation in the Caenorhabditis elegans germline. Genetics. 2022 Mar 3;220(3). doi: 10.1093/genetics/iyab195. Review. PubMed PMID: 35239965; PubMed Central PMCID: PMC8893257.
- Goudeau J, Sharp CS, Paw J, Savy L, Leonetti MD, York AG, Updike DL, Kenyon C, Ingaramo M. Split-wrmScarlet and split-sfGFP: tools for faster, easier fluorescent labeling of endogenous proteins in Caenorhabditis elegans. Genetics. 2021 Apr 15;217(4). doi: 10.1093/genetics/iyab014. PubMed PMID: 33693628; PubMed Central PMCID: PMC8049552.
- Reed KJ, Svendsen JM, Brown KC, Montgomery BE, Marks TN, Vijayasarathy T, Parker DM, Nishimura EO, Updike DL, Montgomery TA. Widespread roles for piRNAs and WAGO-class siRNAs in shaping the germline transcriptome of Caenorhabditis elegans. Nucleic Acids Res. 2020 Feb 28;48(4):1811-1827. doi: 10.1093/nar/gkz1178. PubMed PMID: 31872227; PubMed Central PMCID: PMC7038979.
- Updike DL. Quelling germ cell pluripotency on the genital ridge. Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):25374-25375. doi: 10.1073/pnas.1918899116. Epub 2019 Nov 22. PubMed PMID: 31757856; PubMed Central PMCID: PMC6926031.
- Marnik EA, Fuqua JH, Sharp CS, Rochester JD, Xu EL, Holbrook SE, Updike DL. Germline Maintenance Through the Multifaceted Activities of GLH/Vasa in Caenorhabditis elegans P Granules. Genetics. 2019 Nov;213(3):923-939. doi: 10.1534/genetics.119.302670. Epub 2019 Sep 10. PubMed PMID: 31506335; PubMed Central PMCID: PMC6827368.
- Marnik EA, Updike DL. Membraneless organelles: P granules in Caenorhabditis elegans. Traffic. 2019 Jun;20(6):373-379. doi: 10.1111/tra.12644. Epub 2019 Apr 11. Review. PubMed PMID: 30924287; PubMed Central PMCID: PMC6571499.
- Rochester JD, Tanner PC, Sharp CS, Andralojc KM, Updike DL. PQN-75 is expressed in the pharyngeal gland cells of Caenorhabditiselegans and is dispensable for germline development. Biol Open. 2017 Sep 15;6(9):1355-1363. doi: 10.1242/bio.027987. PubMed PMID: 28916707; PubMed Central PMCID: PMC5612245.
- Andralojc KM, Campbell AC, Kelly AL, Terrey M, Tanner PC, Gans IM, Senter-Zapata MJ, Khokhar ES, Updike DL. ELLI-1, a novel germline protein, modulates RNAi activity and P-granule accumulation in Caenorhabditis elegans. PLoS Genet. 2017 Feb;13(2):e1006611. doi: 10.1371/journal.pgen.1006611. eCollection 2017 Feb. PubMed PMID: 28182654; PubMed Central PMCID: PMC5325599.
- Coffman JA, Rieger S, Rogers AN, Updike DL, Yin VP. Comparative biology of tissue repair, regeneration and aging. NPJ Regenerative Medicine. 2016 June; 1(1):16003.
- Strome S, Updike D. Specifying and protecting germ cell fate. Nat Rev Mol Cell Biol. 2015 Jul;16(7):406-16. doi: 10.1038/nrm4009. Review. PubMed PMID: 26122616; PubMed Central PMCID: PMC4698964.
- Kelly AL, Senter-Zapata MJ, Campbell AC, Lust HE, Theriault ME, Andralojc KM, Updike DL. A Forward Genetic Screen for Suppressors of Somatic P Granules in Caenorhabditis elegans. G3 (Bethesda). 2015 Jun 22;5(10):2209-15. doi: 10.1534/g3.115.019257. PubMed PMID: 26100681; PubMed Central PMCID: PMC4593002.
- Campbell AC, Updike DL. CSR-1 and P granules suppress sperm-specific transcription in the C. elegans germline. Development. 2015 May 15;142(10):1745-55. doi: 10.1242/dev.121434. PubMed PMID: 25968310; PubMed Central PMCID: PMC4440928.
- Updike DL, Knutson AK, Egelhofer TA, Campbell AC, Strome S. Germ-granule components prevent somatic development in the C. elegans germline. Curr Biol. 2014 May 5;24(9):970-5. doi: 10.1016/j.cub.2014.03.015. Epub 2014 Apr 17. PubMed PMID: 24746798; PubMed Central PMCID: PMC4036631.
- Updike DL, Hachey SJ, Kreher J, Strome S. P granules extend the nuclear pore complex environment in the C. elegans germ line. J Cell Biol. 2011 Mar 21;192(6):939-48. doi: 10.1083/jcb.201010104. Epub 2011 Mar 14. PubMed PMID: 21402789; PubMed Central PMCID: PMC3063144.
- Updike D, Strome S. P granule assembly and function in Caenorhabditis elegans germ cells. J Androl. 2010 Jan-Feb;31(1):53-60. doi: 10.2164/jandrol.109.008292. Epub 2009 Oct 29. Review. PubMed PMID: 19875490; PubMed Central PMCID: PMC2905540.
- Updike DL, Strome S. A genomewide RNAi screen for genes that affect the stability, distribution and function of P granules in Caenorhabditis elegans. Genetics. 2009 Dec;183(4):1397-419. doi: 10.1534/genetics.109.110171. Epub 2009 Oct 5. PubMed PMID: 19805813; PubMed Central PMCID: PMC2787428.
- Sheaffer KL, Updike DL, Mango SE. The Target of Rapamycin pathway antagonizes pha-4/FoxA to control development and aging. Curr Biol. 2008 Sep 23;18(18):1355-64. doi: 10.1016/j.cub.2008.07.097. PubMed PMID: 18804378; PubMed Central PMCID: PMC2615410.
- 2012 to 2015 — GSBSE Admissions Committee
- 2013 to 2015 — MDI Bio Lab Seminar Speakers Committee Chair
- 2014 to 2015 — Intro to Development Foundations Course Lecturer
- 2014 to 2015 — MDI Bio Lab Outreach Instructor – Developmental Genetics using C. elegans
- 2016 to present — MDI Bio Lab Outreach Instructor – Genomic Engineering using CRISPR/Cas9
- 2017 to present — Maine INBRE Program Coordinator
- 2013 to 2015 — The role of germ granules in maintaining cellular self renewal and totipotency – from COBRE National Institutes of Health NIGMS
- 2015 to present — The function of germ granules in maintaining pluripotency in the C. elegans germline from R01 – National Institutes of Health NIGMS