Ph.D., University of Colorado, Boulder, 1978
Postdoctoral Research: MRC, Cambridge, England
Lab website: http://www.biochem.wisc.edu/faculty/kimble/
Address: 341E Biochemistry Laboratories
Department: Biochemistry, Molecular Biology and Medical Genetics
Research InterestsMolecular regulation of germline self-renewal and differentiation in C. elegans
Research FieldsDisease Biology
Computational, Systems & Synthetic Biology
Genomics & Proteomics
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.
C.T., Lee, M.-H., and J. Kimble (2010)
Chemical reprogramming of Caenorhabditis
elegans germ cell fate. Nature
Chemical Biology 6, 102-104.
Cinquin, O., Crittenden, S.L., Morgan, D.E. and J. Kimble (2010) Progression from a stem cell-like state to early differentiation in the C. elegans germ line. PNAS 107, 2048-2053.
Kershner, A. and J. Kimble (2010) Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator. PNAS 107, 3936-3941.
Jeong, J., Verheyden, J.M. and J. Kimble (2011) Cyclin E and Cdk2 control GLD-1, the mitosis/meiosis decision, and germline stem cells in Caenorhabditis elegans. PLoS Genetics 7(3), e1001348.
Friend, K., Campbell, Z.T., Cooke, A., Kroll-Conner, P., Wickens, M.P. and J. Kimble (2012) A conserved PUF/Ago/eEF1A complex attenuates translation elongation. Nature Structural and Molecular Biology 19(2), 176-183.
Morgan, C.T., Noble, D. and J. Kimble (2013) Mitosis-meiosis and sperm-oocyte fate decisions are separable regulatory events. www.pnas.org/cgi/doi/10.1073/pnas.1300928110 (Proc Natl Acad Sci U S A. 2013 Feb 11. [Epub ahead of print])