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THE 2008 George W. Beadle Medal for outstanding contributions to the genetics community is awarded to Mark Johnston. Mark has been an important contributor to the genomics revolution through his leadership in sequencing projects and development of new resources and technologies, and he has significantly advanced our understanding of nutrient sensing.
Mark discovered genetics as an undergraduate in Winston Brill's lab at the University of Wisconsin, where he mapped genes for nitrogen fixation in Klebsiella. As a graduate student with John Roth, first at Berkeley and then at the University of Utah, Mark became a "toothpick" geneticist in his quest to understand how expression of the his operon of Salmonella is regulated (JOHNSTON and ROTH 1981). Foreshadowing his future, he became one of the early adopters of Sanger sequencing and used it to reveal the mechanism of attenuation of the his operon. He moved from Utah to Stanford to do postdoctoral work with Ron Davis, where he discovered budding yeast and its GAL genes (JOHNSTON and DAVIS 1984; JOHNSTON and DOVER 1988), and made friends and colleagues with a remarkable group of students and postdocs then in the Department of Biochemistry.
Mark was recruited to the new Department of Genetics at Washington University in 1983. He has remained in St. Louis, where he has made significant scientific contributions to the genetics community in three areas: yeast genomics, glucose sensing, and comparative sequence analysis.
In the early 1990s, encouraged by his colleague and neighbor Bob Waterston who was sequencing the Caenorhabditis elegans genome, Mark went on a mission to contribute to the sequencing of the Saccharomyces cerevisiae genome. Under Mark's guidance, Waterston's Genome Sequencing Center determined the sequence of almost 20% of the yeast genome. Mark became a critical component of the international consortium of investigators that determined the sequence of the 12-Mb yeast genome (JOHNSTON et al. 1994a). He went on to play a pivotal role in the project to individually delete all yeast genes. The resulting yeast gene deletion collection has become an indispensable resource for the yeast community and it has transformed genetic analysis of this organism. This resource has stimulated the development of novel types of genomewide genetic analysis, including synthetic lethality, haplo-insufficiency screens, and synthetic chemical phenotypes (WINZELER et al. 1999; GIAEVER et al. 2002).
Mark's lab has been in the vanguard of studies of cellular nutrient sensing, focusing on how yeast cells sense glucose. Being the most abundant monosaccharide on the planet, glucose is the principal energy source for most cells, and yeasts have evolved sophisticated mechanisms to sense its presence. Mark's lab has concentrated on two glucose-sensing and signal-transduction pathways that regulate gene expression (JOHNSTON et al. 1994b). One pathway causes repression of gene expression by glucose through the Snf1 protein kinase and the Mig1 and Mig2 transcriptional repressors (DEVIT et al. 1997). The other pathway, which regulates expression of HXT genes that encode glucose transporters, starts with two transmembrane glucose sensors discovered in Mark's lab (OZCAN et al. 1998). They are the founding members of a novel class of nutrient receptors that have sequence similarity to the glucose transporters. Mark and his coworkers have traced the glucose signal from the glucose sensors at the cell surface to the transcription factors in the nucleus to decipher this critical cellular process. His lab has recently expanded its focus to include Candida albicans; this work has the potential to identify novel pharmacological approaches for treating bloodstream infections of this pathogenic yeast.
While annotating the yeast genome sequence that was coming off the machines in St. Louis, Mark saw firsthand the difficulty of identifying sequence features that do not encode proteins; these include sequences that regulate gene expression or direct chromosome maintenance. He realized that the process of evolution provided the needed tools: changes in nonfunctional sequences make functional sequence elements stand out in genome sequence comparisons. So Mark collaborated with the Washington University Genome Sequencing Center to produce draft sequences of five yeast genomes. Their experiments were one of the first uses of comparative genome sequence analysis to identify and predict functional sequences in genomes (CLIFTEN et al. 2003). But those results beg for follow-up experiments to decipher regulatory networks, and Mark collaborated with his colleague Rob Mitra and their student Haoyi Wang to engineer "calling cards" for DNA-binding proteins, a new tool that can be used to map their sites of action (WANG et al. 2007).
Like George Beadle, Mark has also made important contributions to science through his leadership roles. He was president of the Genetics Society of America (GSA) in 2004. He launched several new initiatives of the Society, including the biennial meeting of the GSA, "Genetic Analysis: Model Organisms to Human Biology," which seeks to bring geneticists of all stripes together (at least for a few days), and the GSA newsletter GENEtics. He continues his long service as an Associate Editor of GENETICS, the journal of the GSA, and currently chairs the GSA Publications Committee. As a consummate geneticist and a dedicated citizen of the genetics community, Mark is a deserving recipient of the Beadle Medal.
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LITERATURE CITED
CLIFTEN, P., P. SUDARSANAM, A. DESIKAN, L. FULTON, B. FULTON et al., 2003 Finding functional features in Saccharomyces genomes by phylogenetic footprinting. Science 301: 71–76.
DEVIT, M., J. WADDLE and M. JOHNSTON, 1997 Regulated nuclear translocation of the Mig1 glucose repressor. Mol. Biol. Cell 8: 1603–1618.[Abstract]
GIAEVER, G., A. M. CHU, L. NI, C. CONNELLY, L. RILES et al., 2002 Functional profiling of the S. cerevisiae genome. Nature 418: 387–391.[CrossRef][Medline]
JOHNSTON, M., and R. W. DAVIS, 1984 Sequences that regulate the divergent GAL1–GAL10 promoter in Saccharomyces cerevisiae. Mol. Cell. Biol. 4: 1440–1448.
JOHNSTON, M., and J. DOVER, 1988 Mutational analysis of the gal4-encoded transcriptional regulatory protein of Saccharomyces cerevisiae. Genetics 120: 63–74.
JOHNSTON, H. M., and J. R. ROTH, 1981 DNA sequence changes of mutations altering attenuation control of the histidine operon of Salmonella typhimurium. J. Mol. Biol. 145: 735–756.[CrossRef][Medline]
JOHNSTON, M., S. ANDREWS, R. BRINKMAN, J. COOPER, H. DING et al., 1994a Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII. Science 265: 2077–2082.
JOHNSTON, M., J. S. FLICK and T. PEXTON, 1994b Multiple mechanisms provide rapid and stringent glucose repression of GAL gene expression in Saccharomyces cerevisiae. Mol. Cell. Biol. 14: 3834–3841.
OZCAN, S., J. DOVER and M. JOHNSTON, 1998 Glucose sensing and signaling by two glucose receptors in the yeast Saccharomyces cerevisiae. EMBO J. 17: 2566–2573.[CrossRef][Medline]
WANG, H., M. JOHNSTON and R. D. MITRA, 2007 Calling cards for DNA-binding proteins. Genome Res. 17: 1202–1209.
WINZELER, E. A., D. D. SHOEMAKER, A. ASTROMOFF, H. LIANG, K. ANDERSON et al., 1999 Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285: 901–906.
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