Aspergillus nidulans is an ascomycete fungus that is a valuable organism for the study of eukaryotic cell metabolism, growth and differentiation. The study of this organism is of interest because it shares many biological processes with higher organisms. For example: It excretes proteins through it's cell membrane, is susceptible to many of the toxins that harm man, biologically resembles such human pathogens as Aspergillus fumigatus, and shares many of the same mechanisms of controlling gene expression as higher plants and animals. This organism will aid in understanding the biology of related species which are opportunistic pathogens. Industry is also interested in developing this organism as a host for the production of recombinant DNA products many of which will be used as pharmaceuticals in treatment of disease. The isolation of genes controlling the induction and development of asexual spores (conidia) are proposed. The recent characterization of a gene (bristle) that is pivotal in initiating the physical process of conidiation suggests a method for isolating transcriptional regulators of that gene. Gene fusions between the 5' regulatory sequences of bristle, the Aspergillus nidulans alcA and trypC genes, and the E. coli lac z genes are proposed to be used for direct selection of mutant defects in transcriptional regulators of the bristle gene in vivo. beta-galactosidase expression will be used as a reporter gene to readily identify regulatory mutations in these experiments. The use of a reporter gene will allow the detection of genes that specifically regulate bristle as opposed to similar morphological mutants that occur as a result of a variety of other defects. Molecular cloning and DNA sequencing of the regulatory genes will be used to compare these genes to other known regulatory proteins. Isolation of the transcriptional regulators of bristle will permit detailed genetic and molecular biological analysis of a potentially new and exciting type of developmental regulatory mechanism.
