Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been taken by over 4,800 students at 73 institutions. We show here that this alliance-sourced model not only substantially advances the field of phage genomics but also stimulates students’ interest in science, positively influences academic achievement, and enhances persistence in science, technology, engineering, and mathematics (STEM) disciplines. Broad application of this model by integrating other research areas with large numbers of early-career undergraduate students has the potential to be transformative in science education and research training.

The phytohormone cytokinin is an important regulator of plant growth and development; however, relatively few genes that mediate cytokinin responses have been identified. Genome-wide analyses of Arabidopsis seedlings using the approximately 8,300-element Affymetrix Arabidopsis GeneChips (Affymetrix, Santa Clara, CA) to examine cytokinin-responsive genes were conducted, revealing at least 30 genes whose steady-state level of mRNA was elevated and at least 40 that were down-regulated at multiple time points after application of cytokinin. The cytokinin up-regulated genes include the type-A Arabidopsis response regulators (ARRs), which had been shown previously to be cytokinin primary response genes, cytokinin oxidase, which encodes an enzyme that degrades cytokinins, and several transcription factors. Cytokinin down-regulated genes include several peroxidases and kinases and an E3 ubiquitin ligase. We identified a common sequence motif enriched in the upstream regions of the most consistently cytokinin up-regulated genes. This motif is highly similar to the optimal DNA-binding sites for ARR1/ARR2, type-B ARRs that have been implicated in the transcriptional elevation of the type-A ARRs. Additionally, genome-wide analyses of cytokinin receptor mutants (wol/cre1) revealed large-scale changes in gene expression, including down-regulation of the type-A ARRs and several meristem and cell cycle genes, such as CycD3. Mutations in CRE1 reduced but did not eliminate the effect of cytokinin on gene expression for a subset of cytokinin-responsive genes and had little or no effect on others, suggesting functional redundancy among the cytokinin receptors.Cytokinins are a group of adenine derivatives that affect multiple aspects of plant growth and development, including cell division, vascular development, sink/source relationships, apical dominance, and leaf senescence (Binns, 1994; Mok, 1994, 2001). A pathway for cytokinin biosynthesis and metabolism is emerging from molecular and biochemical studies. This has been highlighted by the recent cloning of several genes encoding enzymes involved in cytokinin biosynthesis or metabolism, including ipt (Kakimoto, 2001; Takei et al., 2001), which catalyzes the first committed step in cytokinin biosynthesis; cytokinin oxidase (Houba-Hérin et al., 1999;Morris et al., 1999), which cleaves the N 6 side chain from cytokinins; and several enzymes that catalyze the conjugation of sugar moieties to cytokinins (Martin et al., 1999a(Martin et al., , 1999b(Martin et al., , 2001. A model for cytokinin perception and signal transduction has emerged that is similar to prokaryotic two-component response pathways (Haberer and Kieber, 2001; Hutchison and Kieber, 2002;Lohrmann and Harter, 2002). A family of genes that are similar to bacterial two-component response regulators, the type-A Arabidopsis response regulators (ARRs), was identified as cytokinin primary response genes (Brandstatter and Kieber, 1998;Sakakibara et al., 1998;Taniguchi et al., 1998; D'Agostino et al., 2000). The cytokinin re...

FetA, formerly designated FrpB, an iron-regulated, 76-kDa neisserial outer membrane protein, shows sequence homology to the TonB-dependent family of receptors that transport iron into gram-negative bacteria. Although FetA is commonly expressed by most neisserial strains and is a potential vaccine candidate for bothNeisseria gonorrhoeae and Neisseria meningitidis, its function in cell physiology was previously undefined. We now report that FetA functions as an enterobactin receptor. N. gonorrhoeae FA1090 utilized ferric enterobactin as the sole iron source when supplied with ferric enterobactin at approximately 10 μM, but growth stimulation was abolished when an omega (Ω) cassette was inserted withinfetA or when tonB was insertionally interrupted. FA1090 FetA specifically bound59Fe-enterobactin, with a Kd of approximately 5 μM. Monoclonal antibodies raised against theEscherichia coli enterobactin receptor, FepA, recognized FetA in Western blots, and amino acid sequence comparisons revealed that residues previously implicated in ferric enterobactin binding by FepA were partially conserved in FetA. An open reading frame downstream of fetA, designated fetB, predicted a protein with sequence similarity to the family of periplasmic binding proteins necessary for transporting siderophores through the periplasmic space of gram-negative bacteria. An Ω insertion withinfetB abolished ferric enterobactin utilization without causing a loss of ferric enterobactin binding. These data show that FetA is a functional homolog of FepA that binds ferric enterobactin and may be part of a system responsible for transporting the siderophore into the cell.

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FetA, the recently characterized gonococcal ferric enterobactin receptor, exhibited extremely rapid phase variation between high‐ and low‐expression levels. The frequency of phase variation was ≈ 1.3% in both directions in gonococcal strain FA1090. FetA expression in the ‘high phase’ was significantly greater than the level of expression in the ‘low phase’. Expression levels correlated with the number of cytosine residues in a string of cytosines located close to the transcriptional start site for fetA between the putative −10 and −35 consensus sequences. Antibody production against FetA commonly occurs in infected patients, and we therefore hypothesize that phase variation reflects a balance between the advantages of being able to use a ferric siderophore as an iron source and evasion of the host immune response.