Welcome to the Actinome Project
This ambitious project we have coined "The Actinome Project" has two general goals: 1) To identify the entire actin related gene set using methods to detect physical and genetic interactions, and 2) Correlate these interactions to specific functions of actin. This website, The Actinome Resource Page, will serve as a conduit through which to make accessible to the interested community the data and data analysis tools developed by this project. The initiative for this project comes from the laboratory of Dr. David Amberg at SUNY Upstate Medical University which will be responsible for generation of most of the data. In addition the project currently includes several collaborators: computational biologist Dr. Olga Troyanskaya of Princeton University, Dr. Mike Tyers at the University of Toronto, and Dr. Dan Burke of the University of Virginia.
In some ways this project began many years ago when we summarized the known physical and genetic interactions of actin for a chapter of the Cold Spring Harbor Press publication "The Molecular Biology of the Yeast Saccharomyces; Cell Cycle and Cell Biology" in 1997. Below I have reprinted a Figure from that text showing the known interactions with actin as mined from the literature. At this time we already knew that actin was incredibly functionally diverse, which explains the complexity of this network, but the results of recent complex haplo-insufficiency screens (which can be seen on the front page of this web site) have uncovered 200 interacting genes with a fairly small overlap with this 1997 understanding. Clearly the actin related gene network is going to be extremely rich and complex.
The physical interaction information will be mined from the literature, genome scale data sets on co-purification and two hybrid screening and two-hybrid screening performed in the Amberg lab. The genetic interaction information will be mined from the literature, large scale synthetic lethal screens performed by the Toronto supergroup (Boone, Tyers, and Andrews labs), synthetic lethal screens performed in the Amberg lab with actin alleles and complex haplo-insufficiency screens also performed in the Amberg lab. The tools that will be used to attribute these interactions to specific actin functions will be a large set of rationally designed actin mutants, the actin alanine scan alleles originally constructed in the lab of Dr. David Botstein. The culmination of this analysis will be a genetic based structure/function map of the actin surface, as well as the visual rendering and bioinformatics tools to understand and analyze what is sure to be a complex genetic network.
We presume that many of the genetic interactions of actin will be attributable to effects on the interactions between actin and it binding partners, the actin binding proteins. Therefore, to flush out this structure/function map we will determine which of actin's genetic interactions can be phenocopied by mutations in actin binding protein genes. This idea is cartooned in the figure below. In this simple example, genes YFG1 and YFG2 display genetic interactions with actin alleles 1, 2, and 3 while genes YFG3 and YFG4 genetically interact with actin alleles 3 and 4. The actin-binding protein gene ABP? shows a genetic interaction with YFG1 and YFG2 suggesting that the genetic interactions between actin and YFG1 and YFG2 are due to the loss of binding of Abp? and that actin alleles 1,2 and 3 map the Abp? binding site.
This web site is expected to continue to evolve into a community resource for the deposition and aquisition of any and all information relating to the yeast actin cytoskeleton. More information about the contents of this web site can be found on the Site Map page.