Judith Kimble
Professor of Biochemistry, Molecular Biology and Medical Genetics
Ph.D., University of Colorado, Boulder, 1978
Postdoctoral Research: MRC, Cambridge, England
Lab Website: http://www.biochem.wisc.edu/faculty/kimble/
Address: 341e Biochemistry
Telephone: 262-6188
E-mail: jekimble@wisc.edu
Research Interests:
Molecular regulation of animal development
Research Fields:
Developmental Genetics
C. elegans
Molecular Genetics
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:
Morgan,
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.
Professor of Biochemistry, Molecular Biology and Medical Genetics
Ph.D., University of Colorado, Boulder, 1978
Postdoctoral Research: MRC, Cambridge, England
Address: 341e Biochemistry
Telephone: 262-6188
E-mail: jekimble@wisc.edu
Research Interests:
Molecular regulation of animal development
Research Fields:
Developmental Genetics
C. elegans
Molecular Genetics
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.
Morgan, 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.
