Arnosti Lab "The System"- MSU Biochemistry and Molecular Biology

The System
 

Fundamental principles regarding the nature of genes, chromosomes, evolution, behavior, and development have come directly from studies of Drosophila. Modern molecular techniques wedded to powerful genetics are allowing us to probe the nature of genetic switches that control the flow of information from DNA to RNA, one of life's most fundamental processes.

Early embryogenesis in Drosophila is driven by cascades of transcriptional switches, which are activated and deactivated in complex spatial and temporal patterns. The activity of one such switch protein, Knirps, is demonstrated in the embryo at the left. The lacZ reporter gene is expressed widely in this embryo (blue staining); a vertical white swath seen near the center of the embryo represents a region in which Knirps is repressing the reporter gene.

Many of our experiments involve testing the activity of novel genes or gene products in transgenic organisms. P-element mediated germline transformation, pioneered by Rubin and Spradling, allows us to easily create transgenic Drosophila. A few hours in the injection room with fly embryos, a bit of luck, and a few weeks wait, and you have novel transgenic Drosophila lines.

The combined biochemical, genetic, and molecular biological approaches possible with Drosophila have allowed us to decipher the sophisticated activity of complex gene switches. Ultimately, our studies will allow us to move from a "parts list" view of the genome to a dynamic picture that shows how cryptic regulatory information controls the activity of genes on a global scale.
(Models of transcriptional enhancers, from Kulkarni and Arnosti (2003) Development 130 (26): 6569).
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