RESEARCH PROGRAMS AND AFFILIATIONS
Biochemistry and Molecular Biology
Biomedical Sciences Program
RESEARCH INTERESTS
Regulation of actin dynamics and analysis of genomic influences on actin function.
EDUCATION
Postdoctoral Fellow: Stanford University
PhD: Dartmouth Medical School, 1992
RESEARCH ABSTRACT
My laboratory is interested in how actin associated proteins regulate the assembly and organization of the actin cytoskeleton in eukaryotic cells. The actin protein polymerizes to form dynamic filaments that are central to the organization and remodeling of all eukaryotic cells. Our investigations into actin regulation employ a powerful model organism, the common bread/beer budding yeast called Saccharomyces cerevisiae. The proteins we study are conserved in structure and function thereby allowing us to use powerful tools to unravel their functions with biochemistry, cell biology,''genetic, structural biology and molecular biology techniques. Our current studies are focused on understanding four actin regulators:
- Aip1p catalyzes the fragmentation of existing actin filaments in cooperation with another actin regulator called cofilin.
- Aip3p is a cell cycle controlled spatial regulator of actin polymerization as well as an important facilitator of nuclear segregation during cell division.
- Oye2p (Old Yellow Enzyme) is an NADPH oxidoreductase that repairs oxidative damage to actin. This same damage is a major contributor to sickle cell crisis and therefore our investigation has direct relevance to the treatment of sickle cell disease.
- Ssk2p is a MEK kinase that promotes actin cytoskeleton recovery following osmotic stress. Our goal is to understand the mechanisms by which these proteins regulate actin at an extremely sophisticated level.
Our goals are to: 1) Understand the detailed mechanisms by which these proteins regulate these processes, and 2) To use these projects to train young scientists in the application of modern technologies to important fundamental problems in biology.
Selected References
Scarcelli JJ, Viggiano S, Hodge CA, Heath CV, Amberg DC, Cole CN. Synthetic genetic array analysis in Saccharomyces cerevisiae provides evidence for an interaction between RAT8/DBP5 and genes encoding P-body components. Genetics. 2008 Aug;179(4):1945-55. Epub 2008 Aug 9.
Clark MG, Amberg DC. Biochemical and genetic analyses provide insight into the structural and mechanistic properties of actin filament disassembly by the Aip1p cofilin complex in Saccharomyces cerevisiae. Genetics. 2007 Jul;176(3):1527-39. Epub 2007 May 4.
Haarer BK, Helfant AH, Nelson SA, Cooper JA, Amberg DC. Stable preanaphase spindle positioning requires Bud6p and an apparent interaction between the spindle pole bodies and the neck. Eukaryot Cell. 2007 May;6(5):797-807. Epub 2007 Apr 6.
Bettinger BT, Amberg DC. The MEK kinases MEKK4/Ssk2p facilitate complexity in the stress signaling responses of diverse systems. J Cell Biochem. 2007 May 1;101(1):34-43. Review.
Farah ME, Amberg DC. Conserved actin cysteine residues are oxidative stress sensors that can regulate cell death in yeast. Mol Biol Cell. 2007 Apr;18(4):1359-65. Epub 2007 Feb 7.
Bettinger BT, Clark MG, Amberg DC. Requirement for the polarisome and formin function in Ssk2p-mediated actin recovery from osmotic stress in Saccharomyces cerevisiae. Genetics. 2007 Apr;175(4):1637-48. Epub 2007 Jan 21.
Haarer B, Viggiano S, Hibbs MA, Troyanskaya OG, Amberg DC. Modeling complex genetic interactions in a simple eukaryotic genome: actin displays a rich spectrum of complex haploinsufficiencies. Genes Dev. 2007 Jan 15;21(2):148-59. Epub 2006 Dec 13.
PUBLICATIONS
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