MAJOR RESEARCH ADVANCES

Over time, William Dove and his colleagues have contributed in four distinct areas of genetics and biology:

1) Efficient mutagenesis in Physarum polycephalum and the laboratory mouse, leading to the first extensive university-based program of phenotype-driven genetic analysis of the biological problems special to each of these two experimental organisms (Haugli and Dove, 1972; Schedl et al., 1984a; Shedlovsky et al., 1986; McDonald et al., 1990; and Vitaterna et al., 1994). The Min mouse, generated by germline mutagenesis by ENU (Moser et al., 1990) has provided a platform for genetic, cellular, and molecular studies of multiple intestinal neoplasia in hundreds of laboratories, worldwide. With his McArdle colleague Michael Gould he has now adapted germline ENU mutagenesis to the laboratory rat, obtaining a colon cancer kindred of this mammalian species (Amos-Landgraf, Kwong et al., 2007).

2) The molecular genetics of Physarum polycephalum, from Mendelian dissection of the gene families for the eukaryotic cytoskeleton to opening the molecular analysis of gene function in this organism by DNA transformation (Schedl and Dove, 1982 and Burland et al., 1993).

3) Nested sets, recombination and genetic structure:

• The integrated lambda prophage (Franklin et al., 1965)
• Regions of mammalian chromosomes over which strong positive interference operates (King et al., 1989)
• The importance of somatic recombination in familial colon cancer (Haigis et al, 2002; Haigis and Dove, 2003; Kwong et al, 2007a)

4) Elements of growth control - from DNA replication of phage lambda, through nuclear cycling in Physarum polycephalum, to neoplasia in the intestinal epithelium of mammals:

• Trans-acting positive factors and a cis-acting replication origin of phage lambda, intrinsically activated by local transcription (Dove et al., 1969 and 1971; Furth et al., 1978; and Furth et al., 1979).
• Periodic transcription for regulators of the cell cycle (Laffler et al., 1981 and Schedl et al., 1984b).
  
• Autonomous and non-autonomous negative regulators controlling homeostasis in the intestinal epithelium, identified by the Min, Mom1, and p53 alleles of the mouse and the Pirc allele of the rat (Moser et al., 1990; Su et al., 1992; Dietrich et al., 1993; Gould and Dove, 1997; Cormier et al., 1997; Halberg et al, 2000; and Amos-Landgraf, Kwong et al., 2007).
• A general strategy for the discovery of protectors against cancer predispositions (Dove et al., 1998).
• Strong synergy between complementary factors, each with a mild effect on the growth of a tumor (Cormier and Dove, 2000).
• Polyclonal interactions in the establishment of intestinal neoplasms (Merritt et al., 1997; Thliveris et al., 2005).
• Control of the growth rate of early intestinal adenomas by Atm (Kwong et al, 2007b)
• A general strategy to monitor colonic tumor development in living animals (Pickhardt, Halberg, et al., 2005)