The first step in gene expression is the formation of an RNA copy of its DNA. This step, called transcription, takes place in the cell nucleus. Transcription requires an enzyme called RNA polymerase to catalyze the synthesis of the RNA from the DNA template. This, in addition to other processing factors, is needed before messenger RNA (mRNA) can be exported to the cytoplasm, the area surrounding the nucleus.
Although the biochemical details of transcription and RNA processing are known, relatively little is understood about their cellular organization. Joseph G. Gall has been an intellectual leader and has made seminal breakthroughs in our understanding of chromosomes, nuclei and cells for nearly 60 years. He is particularly interested in how the structure of the nucleus is related to the synthesis and processing of RNA—specifically, what changes occur in the chromosomes and other nuclear components when RNA is synthesized, processed, and transported to the cytoplasm.
The researchers concentrate on a structure in the nucleus called the Cajal body, so named because it was first described 100 years ago by the Spanish neurobiologist and Nobel laureate Ramon y Cajal. Until recently very little was known about the Cajal body, but modern microscopical techniques have brought rapid progress. Cajal bodies are now known to contain many factors involved in transcribing and modifying both pre-messenger RNA and pre-ribosomal RNA. Gall thinks that the Cajal body is a site for assembly of factors required for transcription and RNA processing.
Much of the lab’s work is carried out with unlaid eggs removed from the female frog Xenopus. These eggs, called oocytes, are giant cells up to 1.5 millimeters (mm) in diameter with a nucleus, or germinal vesicle (GV), 0.4 mm in diameter. The large GV permits scientists to examine the contents and structure of the nucleus in unprecedented detail.
The lab also used the fruit fly Drosophila cells , which are much smaller than frog cells, but have the advantage that they permit genetic studies on Cajal body components. In Drosophila one can manipulate the genes that encode proteins and RNAs of the Cajal body, and follow the consequences in various embryonic, larval, and adult tissues.
Gall has received numerous awards in acknowledgment of his special contributions, including the Albert Lasker Special Achievement Award in Medical Research, and the Lifetime Achievement Award of the Society for Developmental Biology, among others.
From 1952 to 1964 Gall taught zoology at the University of Minnesota. From 1964 to1983 he was the Ross Granville Harrison Professor of Biology, Professor of Molecular Biophysics and Biochemistry, at Yale University. In1983 he joined the Carnegie Institution as a staff scientist. For more see the Gall lab