Robert S. Cohen, Ph.D., Professor, Department of Molecular Biosciences (KU-L)
"Polarizing the fly egg and embryo: RNAs on the move"
Many mRNAs are localized to specific cytoplasmic sites prior to their translation as a means of targeting their encoded proteins to regions of the cell where they are needed and/or preventing them from accumulating in regions where they may do harm. The important role that mRNA localization plays in protein targeting is best illustrated in the Drosophila oocyte, where mutations that disrupt mRNA localization result in the production of malformed eggs that give rise to headless or other monstrous embryos that die before hatching. Studies in a variety of systems indicate that mRNAs are localized by one of three general mechanisms: active transport on microtubules; diffusion to a localized trap; and region-specific mRNA degradation. Each localized mRNA contains one or more cis-acting sequence elements (referred to as RNA Localization Elements, RLEs) that specify where the RNA will be localized through the recruitment of proteins that comprise a particular localization machinery. My lab has identified two separate RLEs that mediate mRNA localization to the Drosophila oocyte’s anterior end, most likely through their ability to bind cytoplasmic dynein, a microtubule motor protein. Curiously, each RLE is found in just one or two different mRNA species even though many hundreds of mRNAs are localized to the oocyte’s anterior end. Equally curious, one of the two RLEs exhibits different localization activities, depending on its position within the transcript. These findings underscore the difficulty in predicting RNA localization patterns from DNA sequence data.
Scott Hefty, Ph.D, Associate Professor, Department of Molecular Biosciences (KU-L)
Discovery of Protein Function through Structural Proteomics and Microbicide Development for Chlamydia trachomatis
Chlamydia trachomatis and Chlamydia pneumoniae are among the most significant bacterial pathogens afflicting humans. Despite the enormous impact on public health, surprisingly little is known about these phylogenetically distinct bacteria including aspects of basic biology, genetics, and pathogenesis. One of the primary factors limiting our understanding of the biology and pathogenesis of Chlamydia is the relatively high percentage (~25-35%) of encoded proteins with unknown function. We have addressed this challenge by developing a collaborative structural proteomics project that enlists both computational and experimental approaches. Additionally, given in the absence of a safe and effective vaccine, developing vaginal delivered microbicides effective against C. trachomatis infections is a high priority. Also through collaborative efforts, we have initiated multiple, complimentary and cohesive projects to identify and develop vaginal delivered microbicide components that are safe and effective against C. trachomatis infections.
Joe Lutkenhaus, Ph.D., Distinguished Professor, Department of Microbiology, Molecular Genetics and Immunology (KUMC)
“Bacterial cell division”
Bacterial cell division requires a cytoskeletal element called the Z ring, which is assembled from polymers of FtsZ, the ancestral homologue of eukaryotic tubulin. The Z ring functions as a scaffold to recruit additional cell division proteins to make a large protein machine called the divisome, which divides the bacterial cell. The position of the Z ring is restricted to the middle of the cell by a negative regulatory system called, the Min system. This system encodes three proteins (MinC, MinD and MinE), which prevent Z ring formation away from midcell through an oscillatory mechanism. We have used a combined genetic and biochemical approach to understand this oscillatory mechanism, which involves the dynamic interaction of these proteins with the membrane driven by ATP hydrolysis.