W. Allen Miller was born and raised in River Forest, IL. He graduated cum laude with a B.A. degree with distinction in biology from Carleton College in 1978. In 1984, he earned a Ph.D. degree in molecular biology from the University of Wisconsin in Madison, in the laboratory of Timothy C. Hall. His graduate research focused on the mechanisms by which Brome mosaic virus replicase recognizes its template and initiates RNA synthesis, including the discovery of the process by which many positive-strand RNA viruses synthesize subgenomic mRNAs.
From 1984 until 1988, Miller served as a research scientist in the laboratory of Wayne L. Gerlach and Peter M. Waterhouse at the CSIRO Division of Plant Industry in Canberra, Australia. There, he determined the complete nucleotide sequence of the genome of Barley yellow dwarf virus (BYDV), the first for any virus in the family Luteoviridae, and he codiscovered and sequenced the first known satellite RNA of BYDV (an isolate now known as Cereal yellow dwarf virus [CYDV]). The yellow dwarf viruses are considered to be the most economically important and ubiquitous viruses of wheat, barley, and oats worldwide. Until Miller sequenced the BYDV genome, very little was known about BYDV molecular biology despite its agricultural importance. Miller’s sequence, along with subsequent sequences determined in the lab of APS Fellow Richard Lister, forced a reclassification of luteoviruses (to which Miller contributed as a member of the ICTV Committee on Luteoviridae), most notably the split of the different BYDV serotypes into two different genera.
Since joining the Iowa State University (ISU) faculty in 1988, Miller has become one of the world’s leading authorities on mechanisms of BYDV molecular biology. Miller’s research has made important contributions to several disciplines, including RNA structure and function and the fundamental mechanisms of eukaryotic protein synthesis. His strategy has been to transfer knowledge and techniques between fields that often do not interact. He applied state-of-the-art discoveries in the field of translation mechanisms from nonplant systems to the plant world. By attending conferences and publishing in journals that do not focus on plants or pathogens, Miller has made the greater molecular biology world more aware of plant viruses as fascinating model systems that have provided insight on novel RNA interactions and translation processes unknown elsewhere in any biological system.
Miller’s laboratory discovered that translational control signals in an mRNA can consist of separate domains, thousands of bases apart, that must interact for the translation event to take place. He showed that the sequence that mediates efficient translation of BYDV RNA in the absence of the 5¢ “cap” structure is located in the 3¢ untranslated region and it base pairs to the 5¢ untranslated region. This interaction of just five base pairs separated by a four-kilobase loop to control translation was unprecedented in any known eukaryotic or prokaryotic RNA. These results led to the proposal of an elegant “RNA traffic signal” model by which the long-distance interactions may mediate the switch from translation to replication of the viral genome. His novel research findings may have wide application as tools for high-level expression of transgenes. The BYDV cap-independent translation enhancer has been developed into a product that is now available commercially from the biotechnology company Promega. His work has also attracted attention from scientists working with human pathogens as diverse as dengue and SARS viruses.
Miller has made seminal discoveries on mechanisms of recoding in plants. Recoding occurs when a sequence in an mRNA programs the ribosomes to decode the message in a noncanonical way. Examples include ribosomal frameshifting and stop codon readthrough. Miller’s lab was the first to show that ribosomal frameshifting occurs in plants, and Miller and colleagues identified the sequences and structures in BYDV RNA required for frameshifting in the polymerase gene and for readthrough of the coat protein gene stop codon. In both cases, unlike any recoding signals known previously, some of the required signals are located hundreds to thousands of bases downstream of the recoding event.
Miller also identified a hammerhead ribozyme in the CYDV (formerly BYDV) satellite RNA that forms novel alternative structures. Miller and colleagues showed that CYDV satellite RNA can be replicated by any virus with a polerovirus RNA-dependent RNA polymerase.
Miller’s detailed analyses of luteovirus genomes, including dozens of diverse yellow dwarf virus genomes sequenced recently in his lab, allowed him and colleagues to show that luteoviruses and poleroviruses (formerly subgroup I and subgroup II luteoviruses, respectively) probably evolved by replicase strand switching at subgenomic RNA promoters. The identification of these and other recombination hot spots has important implications for luteovirus evolution, ecology, and resistance breeding. In a practical application, Miller and collaborator David Somers (formerly of the University of Minnesota) showed that transgenic oats transformed with part of the BYDV genome recovered rapidly from virus infection.
Recently, Miller turned his attention to interactions of viruses with aphids, the vectors of Luteoviridae and many other plant viruses. Miller and collaborator Bryony Bonning (ISU) have developed tools, including host cell lines and a full-length infectious clone, to investigate replication of Rhopalosiphum padi virus, a pathogen of the major aphid vector of BYDV.
The stimulating research environment provided by Miller has attracted many excellent students and postdocs to his lab. Fifteen students have been awarded Ph.D. degrees under his advice, five received M.S. degrees, and seven worked as undergraduate researchers in his lab. He served as an advisor for 13 postdocs. Miller’s research has been diverse by today’s standards of highly specialized scientists. He has been invited to present talks at international meetings and to write review articles in highly reputed journals and books on all of the above topics. The research has been published in well-respected journals and resulted in two patents and a commercial molecular biology product.
Miller has been tapped to serve in a variety of prestigious roles, including the ICTV Luteoviridae Committee, the Editorial Board of Virology, multiple grant review panels for the USDA National Research Initiative (plant-microbe associations), the NSF Molecular and Cellular Biology division (biochemistry of gene expression), and NIH virology study sections. Recently, he completed a 3-year term as chair of the molecular, cellular, and developmental biology graduate program at ISU. In 2006, he was appointed director of the Center for Plant Responses to Environmental Stresses in the Plant Sciences Institute of ISU.