Organisms in the genus Naegleria offer special opportunities for resea
rch in contemporary biology. The dramatic cell differentiation from am
ebae to flagellates is unique among eukaryotes in the rapidity, synchr
ony, reproducibility, homogeneity, and accessibility of a major phenot
ypic change. Environmental signals initiate a progressive signal trans
duction pathway in which genes are turned on, including those for seve
ral calcium-binding proteins, and newly synthesized proteins become lo
calized in newly assembled organelles, including the centriole-like ba
sal bodies, with the overall consequence that the cell changes its sha
pe, motility, and behavior. This essay reviews research opportunities
for which Naegleria excels, as well as interesting aspects of its biol
ogy that provide challenges for future investigations. Because these o
rganisms alternate between two major eukaryotic motility forms, their
phylogenetic position is also provocative. Although there are hints th
at Naegleria is capable of sexual reproduction in nature, mating has n
ot yet been observed in the laboratory. In order to fully exploit the
opportunities offered by this wonderful experimental system we are wor
king to develop means to do genetic manipulation, in particular via DN
A-mediated transformation.