The Ware lab studies components of one of the most abundant and complex machines in all cells – the ribosome.
This complex of several ribosomal RNAs and multiple ribosomal proteins is the macromolecular “stage” on which all proteins are synthesized in cells in a process called translation. As an essential complex in all cells, the ribosome varies in composition and structure between different organisms, prompting questions of how those structural differences may affect translation or the regulation of translation in different types of cells.
Using biochemical, cellular, genetic, and molecular approaches, the Ware lab is studying differences in ribosome composition and biogenesis at the RNA and protein levels in the fruit fly, Drosophila melanogaster. We are studying the eukaryotic-specific eRpL22 ribosomal protein family where duplicate genes encoding eRpL22 and eRpL22-like (called paralogues) are present to determine if paralogue roles within the ribosome are redundant and to determine if paralogues specify novel, extra-ribosomal roles. Functional differences may have evolved over time, allowing for the development of new or refined functions for these ribosomal protein paralogues. Tissue-specific expression of eRpL22 paralogues in the fly testis and developing eye has provided evidence that paralogue functions are not completely redundant. Our recent investigations support a role in translation regulation for paralogue-specific ribosomes within the male germline, demonstrating that subsets of mRNAs and noncoding RNAs are differentially-enriched on polysomes containing either eRpL22 or eRpL22-like. We propose that ribosome heterogeneity (here illustrated by assembly of different eRpL22 paralogues into ribosomes) defines “specialized ribosomes” with a role in regulating translation of different mRNAs during spermatogenesis. The mechanism for RNA selection on specific ribosome types is currently under investigation.
Ware lab research focuses on phage biology and functional genomics
Phage biology research in the Ware lab was spawned from research in Lehigh University’s SEA-PHAGES Program (sponsored by HHMI). Beyond the SEA-PHAGES goals of discovery of novel actinobacteriophages and phage genome annotation, the Ware lab focuses on characterization of novel phage genes with roles in host defense mechanisms against heterotypic phage infection, particularly in cluster N mycobacteriophages that infect the host, Mycobacterium smegmatis. Multiple defense systems, encoded by genes expressed from cluster N prophage Butters, specifically target certain phage types, but not others. Several phage genes have orthologues in bacterial species, including several human pathogens. We are investigating these prophage-encoded genes to uncover mechanisms of defense to provide insights into strategies employed by phages and their hosts to counter viral attacks. This work has implications for implementation of phage therapy, for developing phage-resistant bacterial strains for use in industry and biotechnology, and for the use of phage proteins as potential biocontrol agents to mitigate the impact of several bacterial pathogens.