Judith Kimble

Research Description:
The Kimble lab investigates fundamental controls of animal development with a focus on stem cells and differentiation. Our work takes advantage of the genetic power and cellular simplicity of the nematode Caenorhabditis elegans, which can be viewed as the “E. coli of animal development”. Our findings rely on a variety of experimental strategies and have uncovered genes, proteins and pathways that control development in all animals, including humans.

A stem cell niche and its control of germline stem cells. A stem cell niche is the ‘external microenvironment’ controlling stem cell maintenance. In C. elegans, the mesenchyal Distal Tip Cell (DTC) niche employs Notch signaling for germline stem cell (GSCs) maintenance. One Notch target gene encodes FBF-2, an RNA-binding protein and broad-spectrum regulator of differentiation. We currently analyzing other Notch target genes and analyzing the extent of Notch signaling within the niche.

The sperm-oocyte cell fate decision. How a germ cell decides to differentiate as a sperm or oocyte remains a mysterious biological feat. Signaling from somatic tissues is critical in all organisms, but how the germ cell responds to that signaling has been largely intractable. In C. elegans, fog-1 and fog-3 specify the sperm fate: germ cells lacking fog-1 or fog-3 make oocytes instead of sperm. We currently are analyzing the relationship between FOG-1 and FOG-3 and their molecular mechanism of function. We can chemically reprogram the sperm-oocyte decision and are using high throughput sequencing to identify RNAs that change upon reprogramming.

Network for germline fate regulation. Our work has outlined a molecular network that regulates the decision between germline self-renewal and differentiation as sperm or oocyte. Many regulators in this network control mRNA translation or stability. We are beginning to address how the network is modulated in response to physiological and environmental cues.

Representative Publications:
Search PubMed for more publications by Judith Kimble

Porter, D.F., Prasad, A., Carrick, B., Kroll-Conner, P., Wickens, M. and J. Kimble (2019) Toward identifying subnetworks from FBF binding landscapes in Caenorhabditis spermatogenic or oogenic germlines. G3: Genes|Genomes|Genetics 9(1), 153-165. PMCID:PMC6325917

Lee, C., Shin, H and J. Kimble (2019) Dynamics of Notch-dependent transcriptional bursting in its native context. Developmental Cell 50(4), 426-435. PMCID:PMC6724715

Haupt, K.A, Law, K.T., Enright, A.L., Kanzler, C.R., Shin, H., Wickens, M.A., and J. Kimble (2019) A PUF hub drives self-renewal in C. elegans germline stem cells. Genetics 214(1), 147-161. PMCID:PMC6944405

Robinson-Thiewes, S, McCloskey J, Kimble J (2020) Two classes of active transcription sites and their roles in developmental regulation. Proc Natl Acad Sci USA doi: 10.1073/pnas.2013163117. PMCID:PMC7604424

Aoki, Scott Takeo, Lynch, Tina R, Crittenden, Sarah L, Bingman, Craig A, Wickens, Marvin, and Judith Kimble (2021) C. elegans germ granules require both assembly and localized regulators for mRNA repression. Nat Commun. 12(1):996. doi: 10.1038/s41467-021-21278-1. PMCID: PMC7881195

Lynch, T.R., Xue, M., Czerniak, C., Lee, C., and Kimble, J. (2022). “Notch-dependent DNA cis-regulatory elements and their dose-dependent control of C. elegans stem cell self-renewal” Development, 149, doi: 10.1242/dev.200332. PMID: 35394007

Kimble, Judith and Christiane Nüsslein-Volhard (2022) The great small organisms of developmental genetics: Caenorhabditis elegans and Drosophila melanogaster. Developmental Biology, 485, 93-122, https://doi.org/10.1016/j.ydbio.2022.02.013