This work, employing Neurospora crassa, is aimed at understanding the metabolic regulation of gene activity. A unifying question is being asked in three otherwise quite distinct lines of work: how do different nuclei in a common cytoplasm share the responsibilities of metabolism? (This question is important in human muscle, which is similarly organized). The first line is on structure and interaction of the mating type genes. Before the nuclear fusion associated with sexual reproduction, the two mating type alleles must communicate through the cytoplasm, accept one another as partners, and set the state for what follows. Under conditions unsuitable for mating, the two types recognize one another as """"""""non-self"""""""" and kill any fused cells along their border. Non-self rejection is a human defense mechanism which can fail when it is needed (as in failing to reject a tumor cell) or work when it shouldn't (as in immunologically destroying one's own endocrine pancreas). The proposed research will use classical and molecular genetics to understand what elements of gene structure allow acceptance of non-self during mating and rejection during vegetative growth. A second line of work is on the structure and interaction of genes regulating phosphorus metabolism. A major question is how the product of a gene called nuc-1+ turns on the expression of other genes needed to supply phosphorus in times of scarcity. The turning on and turning off of expression of genes is central to an understanding of metabolic diseases, and as new insights are developed, they should be applicable to the control of human disease states. The third line is on the regulation of the ribosomal DNA -- how the number of copies of the basic repeat unit are increased or decreased, and where the growth or shrinkage occurs (at the ends? in the middle?). An attempt will be made to produce strains with a mixture of nuclei, in which one kind of nucleus makes all of the ribosomes and the other kind makes a necessary messenger RNA to program those ribosomes. The degree to which labor can be devided between nuclei will be studied.
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