Science Education Alliance Research Articles

SEA-PHAGES and SEA-GENES: Advancing Virology and Science Education.

Research opportunities for undergraduate students are strongly advantageous, but implementation at a large scale presents numerous challenges. The enormous diversity of the bacteriophage population and a supportive programmatic structure provide opportunities to engage early-career undergraduates in phage discovery, genomics, and genetics. The Science Education Alliance (SEA) is an inclusive Research-Education Community (iREC) providing centralized programmatic support for students and faculty without prior experience in virology at institutions from community colleges to research-active universities to participate in two course-based projects, SEA-PHAGES (SEA Phage Hunters Advancing Genomic and Evolutionary Science) and SEA-GENES (SEA Gene-function Exploration by a Network of Emerging Scientists). Since 2008, the SEA has supported more than 50,000 undergraduate researchers who have isolated more than 23,000 bacteriophages of which more than 4,500 are fully sequenced and annotated. Students have functionally characterized hundreds of phage genes, and the phage collection has fueled the therapeutic use of phages for treatment of Mycobacterium infections. Participation in the SEA promotes student persistence in science education, and its inclusivity promotes a more equitable scientific community.

A genome-wide overexpression screen reveals Mycobacterium smegmatis growth inhibitors encoded by mycobacteriophage Hammy.

During infection, bacteriophages produce diverse gene products to overcome bacterial antiphage defenses, to outcompete other phages, and to take over cellular processes. Even in the best-studied model phages, the roles of most phage-encoded gene products are unknown, and the phage population represents a largely untapped reservoir of novel gene functions. Considering the sheer size of this population, experimental screening methods are needed to sort through the enormous collection of available sequences and identify gene products that can modulate bacterial behavior for downstream functional characterization. Here, we describe the construction of a plasmid-based overexpression library of 94 genes encoded by Hammy, a Cluster K mycobacteriophage closely related to those infecting clinically important mycobacteria. The arrayed library was systematically screened in a plate-based cytotoxicity assay, identifying a diverse set of 24 gene products (representing ∼25% of the Hammy genome) capable of inhibiting growth of the host bacterium Mycobacterium smegmatis. Half of these are related to growth inhibitors previously identified in related phage Waterfoul, supporting their functional conservation; the other genes represent novel additions to the list of known antimycobacterial growth inhibitors. This work, conducted as part of the HHMI-supported Science Education Alliance Gene-function Exploration by a Network of Emerging Scientists (SEA-GENES) project, highlights the value of parallel, comprehensive overexpression screens in exploring genome-wide patterns of phage gene function and novel interactions between phages and their hosts.

Complete genome sequences of cluster G1 and cluster K4 Mycobacterium smegmatis phages omnicritical and Barkley26.

We present the complete genome sequence of two Actinobacteriophages, OmniCritical and Barkley26, isolated in Clark County, NV. Over two semesters, The University of Nevada, Las Vegas (UNLV) students isolated and purified phages and manually annotated the genomes. The courses follow the HHMI Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Sciences (SEA-PHAGES) curricula.

Study on the influence of social support on the effect of science education in rural primary schools

This paper analyses the influence of different social support on the effect of science education in rural primary schools, based on the data of rural primary school teachers in 5 re¬gions of Heilongjiang Province in China. The study found that the independent effects of the five social supports such as economic support, the support of science education venues, the guidance of science education and teaching on-site, improvement training of science teacher quality, serve as a science education counsellor on the effect of science education in rural primary schools were significant. The improvement training of science teacher quality and the guidance of science education and teaching on-site still has a great influence on the effect of science education in rural primary schools under the background of different school characteristics, and under sufficient and insufficient capital of science teaching. However, the impact of economic support, the support of science education venues, serving as a science education counsellor is not significant. Therefore, in order to better provide high-quality social support for science education in rural primary schools, a multi-subject science education alliance, led by the county educational administrative departments, should be established to improve coordination and matching degree of social support resource. A science education demand evaluation system, should be established in rural primary schools, to enhance the accuracy of social support services. The quality improvement of science teachers should be taken as the core of social support to clarify the direction of social support.

Wildy Prize Lecture, 2020-2021: Who wouldn't want to discover a new virus?

Innovations in science education are desperately needed to find ways to engage and interest students early in their undergraduate careers. Exposing students to authentic research experiences is highly beneficial, but finding ways to include all types of students and to do this at large scale is especially challenging. An attractive solution is the concept of an inclusive research education community (iREC) in which centralized research leadership and administration supports multiple institutions, including diverse groups of schools and universities, faculty and students. The Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Sciences (SEA-PHAGES) programme is an excellent example of an iREC, in which students explore viral diversity and evolution through discovery and genomic analysis of novel bacteriophages. The SEA-PHAGES programme has proven to be sustainable, to be implemented at large scale, and to enhance student persistence in science, as well as to produce substantial research advances. Discovering a new virus with the potential for new biological insights and clinical applications is inherently exciting. Who wouldn’t want to discover a new virus?

High school science fair: Experiences of two groups of undergraduate bioscience students.

Science fairs offer potential opportunities for students to learn first-hand about the practices of science. Over the past six years we have been carrying out voluntary and anonymous surveys with regional and national groups of high school and post high school students to learn about their high school science fair experiences regarding help received, obstacles encountered, and opinions about the value and impact of science fair. Understanding what students think about science fairs will help educators make science fairs more effective learning opportunities. In this paper, we focus on the findings with two national groups of post high school students–undergraduate research fellows (SURF students) who did research at UT Southwestern Medical Center during 2014–2019 and undergraduates biology students attending the 2019 Howard Hughes Medical Institute Science Education Alliance (SEA) summer symposium. About 25% of the students who completed surveys indicated that they had participated in high school science fair, but more than half attended high schools where science fairs were unavailable. Effectively, 6 out of every 10 students participated in science fair if available. Students who could have participated in high school science fair but chose not to do so identified not enough time and coming up with their project idea as major reasons why not. About half the SURF students favored requiring non-competitive science fair regardless whether they themselves had participated in science fair. On the other hand, less than 1 in 5 thought that competitive science fair should be required. Introduction to the scientific process and general learning were mentioned most frequently as the reasons to require non-competitive science fair; these reasons were mentioned rarely in connection with competitive science fair. Unlike the national cohort of high school students we surveyed previously, who mostly did science fair in 9th and 10th grades, SURF students participated in science fair throughout high school and were twice as likely as high school students to have carried out science fair more than once. In conclusion, our findings suggest that participation of the undergraduate bioscience majors in high school science fairs occurs far more frequently than recognized previously and provide insights into how these successful college students (gauged by the fact that they are doing summer science research) view science fairs. The findings emphasize further the importance of incentivizing rather than requiring science fair participation, especially in 9th and 10th grades, and the potential value of developing non-competitive science fairs.

Actinobacteriophages: Genomics, Dynamics, and Applications.

Actinobacteriophages are viruses that infect bacterial hosts in the phylum Actinobacteria. More than 17,000 actinobacteriophages have been described and over 3,000 complete genome sequences reported, resulting from large-scale, high-impact, integrated research-education initiatives such as the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Sciences (SEA-PHAGES) program. Their genomic diversity is enormous; actinobacteriophages comprise many architecturally mosaic genomes with distinct DNA sequences. Their genome diversity is driven by the highly dynamic interactions between phages and their hosts, and prophages can confer a variety of systems that defend against attack by genetically distinct phages; phages can neutralize these defense systems by coding for counter-defense proteins. These phages not only provide insights into diverse and dynamic phage populations but also have provided numerous tools for mycobacterial genetics. A case study using a three-phage cocktail to treat a patient with a drug-resistant Mycobacterium abscessus suggests that phages may have considerable potential for the therapeutic treatment of mycobacterial infections.

Exploring experiential opportunity impacts on undergraduate outcomes in the geosciences

Undergraduate research is a highly valued and increasingly critical component of STEM undergraduate education, as it is a key strategy in effective student development (National Academies of Sciences, Engineering, and Medicine, 2017; Science Education Alliance, 2017). However, there is little evidence on the long-term education and career impacts of undergraduate research. According to Carlone and Johnson (2007), developing an identity as a scientist requires knowledge growth, the ability to communicate scientific ideas and findings to a variety of audiences, and being recognized and respected as a scientist by others in the field. The goal of this study was to assess the longitudinal differences in science identity development as it relates to education and career outcomes of recipients and nonrecipients of NOAA’s Undergraduate Research Experiences (UREs), the Educational Partnership Program Undergraduate Scholarship, and the Hollings Undergraduate Scholarship. This evaluative study uses a quasi-experimental design to assess differences in students with equal motivation to participate in the URE, as all participants were eligible to apply and completed applications. Multivariate analyses showed that recipients of NOAA’s UREs were 1.2 times more likely to publish in a peer-reviewed journal, 2.2 times more likely to attain an advanced degree, and 1.92 times more likely to be a part- or full-time employee of NOAA.

Investigating Impact of Mycobacterial Physiology on Mycobacteriophage Life Cycles by Mass Spectrometry

Phage‐bacteria interaction plays an important role in both ecology and evolution. Phages lyse bacterial cells to keep nutrient and energy flows of the environment. Arm‐race between phages and bacteria drives evolution of both phages and bacteria. Current phage infection model demonstrates two typical types of phage‐bacteria interaction: lytic and lysogenic cycles. However, the model emphasizes the actions of individual phage particle and bacterial cell. Several researches have unveiled that phage‐bacteria interaction is behavior of both phage and bacterial communities, and a portion of bacterial cells can turn unsusceptible for phage infection. Since phage infection is initiated after the attachment of phage particles to bacterial cells, bacterial surface properties may impact phage‐bacteria interaction. Mycobacterium smegmatis (M. smegmatis) has a thick lipid‐rich cell envelop. Previous researches elucidated that glycopeptidolipids (GPLs) in cell envelope are involved in cell surface properties, receptors of phages and colony morphology of M. smegmatis. Therefore, GPLs may impact phage‐bacteria interaction. Besides GPLs, unique lipids including monomycoloyl trehaloses (MMTs) and triacyl glycerols (TAGs) of M. smegmatis may also impact phage‐bacteria interaction. As morphologies of both M. smegmatis cell and colony change with cell growth phase, composition of envelop lipids (GPLs, MMTs, TAGs etc.) and proteins may change with growth phage, which ultimately lead to alteration of phage‐bacteria interaction. To explore how the mycobacterial physiology affects mycobacteriophage life cycles, the impact of bacterial lipids and proteins composition change on phage and bacterial populations need to be investigated.Five mycobacteriophages from diverse clusters were selected to infect M. smegmatis cell cultures at early exponential and stationary phases for ten hours. Populations of both phages and bacterial cells were determined over time. After four and ten hours of infection, total proteins and lipids were extracted from subsamples of phage‐bacteria mixture, and further analyzed by mass spectrometry. The overall objective of this project is to figure out how phage life cycle alters when bacterial growth phase changes, and which proteins and lipids may be involved. The findings will provide a better understanding of phage‐host interactions over time and contribute towards novel applications in biotechnology.Support or Funding InformationHoward Hughes Medical Institute, Science Education Alliance; Polytechnic Institute, Purdue University; Department of Agricultural and Biological Engineering, Purdue University; Biotechnology Innovation and Regulatory Science Center, Purdue UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Scaling Up: Adapting a Phage-Hunting Course to Increase Participation of First-Year Students in Research.

Authentic research experiences are valuable components of effective undergraduate education. Research experiences during the first years of college are especially critical to increase persistence in science, technology, engineering, and mathematics fields. The Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) model provides a high-impact research experience to first-year students but is usually available to a limited number of students, and its implementation is costly in faculty time and laboratory space. To offer a research experience to all students taking introductory biology at Gonzaga University (n = 350/yr), we modified the traditional two-semester SEA-PHAGES course by streamlining the first-semester Phage Discovery lab and integrating the second SEA-PHAGES semester into other courses in the biology curriculum. Because most students in the introductory course are not biology majors, the Phage Discovery semester may be their only encounter with research. To discover whether students benefit from the first semester alone, we assessed the effects of the one-semester Phage Discovery course on students' understanding of course content. Specifically, students showed improvement in knowledge of bacteriophages, lab math skills, and understanding experimental design and interpretation. They also reported learning gains and benefits comparable with other course-based research experiences. Responses to open-ended questions suggest that students experienced this course as a true undergraduate research experience.

Innovations in Undergraduate Science Education: Going Viral.

Bacteriophage discovery and genomics provides a powerful and effective platform for integrating missions in research and education. Implementation of the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) program facilitates a broad impact by including a diverse array of schools, faculty, and students. The program generates new insights into the diversity and evolution of the bacteriophage population and presents a model for introducing first-year undergraduate students to discovery-based research experiences.

Validation of Mycobacteriophage Genome Annotation by Mass Spectrometry

Mycobacteriophages are viruses that infect Mycobacteria. Phage proteins are traditionally studied by nucleotide sequence based methods. Phage host interactions are complex and thus it is important to validate in silico annotations with a wet lab also examining the phage-host interaction. In this research, fifteen mycobacteriophages isolated through the Howard Hughes Medical Institute (HHMI) Science Education Alliance (SEA) were examined by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Phage samples were incubated with host cell culture overnight, proteins extracted, digested and subjected to LC-MS/MS. The results were analyzed using Mascot and peptides of host cells and phages were identified by searching MS spectral data in separate bioinformatics databases. We found the proteomic data could be used to cluster new phages based upon protein comparison with previously characterized phage genomes. We detected unexpected peptides that were not predicted by the genome annotation. Our findings highlight the importance to examining the phage-host system and future research will explore the impact of phage-host interaction and the phage life cycle on the expression of phage proteins. This program has received funding from HHMI SEA, Purdue University COT and ABE.

Mycobacteriophages: Windows into Tuberculosis

Mycobacteriophages are viruses that infect mycobacterial hosts, such as Mycobacterium tuberculosis and Mycobacterium smegmatis [1]. Because the discovery and genomic characterization of mycobacteriophages has been the focus of integrated research and education programs, including the Phage Hunters Integrating Research and Education (PHIRE) and the Howard Hughes Medical Institute Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (HHMI SEAPHAGES), thousands of phages have been isolated using a single host strain, M. smegmatis mc155, over 500 of which have been completely sequenced [2–5]. These are mostly from environmental samples, but mycobacteriophages have also been isolated from stool samples of tuberculosis patients [6], although these have yet to be genomically analyzed. Clearly, these mycobacteriophages represent only a tiny piece of the overall phage population, which is predicted to include 10 particles, making them the majority of all life-forms in the biosphere [7]. Mycobacteriophages display a remarkable genetic diversity (Figure 1). About 30 distinct types (called clusters, or singletons if they have no relatives) that share little or no nucleotide sequence similarity have been identified. Many of the clusters span sufficient diversity that the genomes warrant division into subclusters (Figure 1). However, the genomes are characteristically mosaic in their architecture [8], which is readily evident from the shared genes revealed by amino acid sequence comparisons [9]. There is also considerable range in overall guanine plus cytosine content (GC%), from 50.3% to 70%, with an average of 64% (M. smegmatis is 67.3%). Thus, phage GC% does not necessarily match that of its host, and the consequent mismatch of codon usage profiles does not appear to be detrimental. Because new mycobacteriophages lacking extensive DNA similarity with the extant collection are still being discovered, and as there are at least seven singletons for which no relatives have been isolated, we clearly have yet to saturate the diversity of this particular population. The pace of discovery is rapid, so the profile of diversity is constantly changing. The collection of .50,000 genes can be sorted into .3,900 groups (phamilies) according to their shared amino acid sequences. Most of these phamilies (,75%) do not have homologues outside of the mycobacteriophages and are of unknown function. Extrapolation to the broader population suggests that phages have the largest repertoire of unexplored sequences in nature. Genetic studies with mycobacteriophage Giles show that 45% of the genes are nonessential for lytic growth, raising questions as to how and why they were acquired [10].

A Broadly Implementable Research Course in Phage Discovery and Genomics for First-Year Undergraduate Students

ABSTRACTEngaging 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.

Phage Renaissance: New Hope against Antibiotic Resistance

In the 1920s and 1930s, before widespread use of anti-biotics, physicians successfully treated a variety of infections with bacteriophages, or phages for short. These natural viral predators, which target bacteria but leave mammalian and plant cells unscathed, were sold by pharmaceutical companies including Eli Lilly & Company1 and even made it into the fiction of the time—the protagonist of Sinclair Lewis’ 1925 book Arrowsmith fought bubonic plague with phages.2 Phages on the surface of an Escherichia coli cell inject genetic material into the bacterium. Scientists of the day did not understand exactly how phages killed bacteria, and their crude therapies performed inconsistently. So with the mass production of “magic bullet” antibiotics in the 1940s and 1950s, interest in phages largely waned.1 But 60 years later, antibiotics are losing their luster. Antibiotics have not only been used to treat human infections but also are given to farm animals to speed growth and prevent illness. They end up being flushed down drains and leach into soil and groundwater, where they contribute to environmental hot spots of antibiotic resistance.3 Antibiotic-resistant microbes now pose a growing threat to people of all ages, nationalities, and socioeconomic backgrounds, and previously treatable diseases are becoming untreatable once more.4 Researchers, too, are looking back to the pre-antibiotic era, but with the goal of resurrecting phages as antidotes for antibiotic resistance and solving medical, agricultural, and environmental problems. This time around, they are armed with molecular biology tools to better understand and control phages. They can also draw on the experience of Eastern European investigators, who have continued to study these viruses for decades, publishing their work primarily in Russian, Georgian, and Polish journals.1 In these countries, phages have continued to be given orally as tablets and liquids, topically, rectally, and as injections for 90 years. No reports of serious side effects have been recorded, and fever and other minor side effects came from contaminants like endotoxins in early phage preparations.1

Phage Hunters Advancing Genomics and Evolutionary Science (PHAGES): Implementing a Research-based Course for Freshmen at the University of North Texas

Paper describes the Phage Hunters Advancing Genomics and Evolutionary Science (PHAGES) program from the Howard Hughes Medical Institute’s Science Education Alliance as implemented at the University of North Texas.

Forging a 21st Century Model for Undergraduate Research

Not all biology students get to experience scientific research firsthand, but the National Genomics Research Initiative (NGRI) is working to change that, says its director, Tuajuanda Jordan. “The goal is to support educators and improve the number and quality of 21st century scientists,” Jordan says. The NGRI is the first initiative to spring from Howard Hughes Medical Institute’s (HHMI) new Science Education Alliance (SEA). At present, a competitive application process determines which institutions become part of NGRI. The goal is to make the experience readily available to all who are interested within the next few years. Participating faculty receive curricular resources and a framework to infuse genomic research into a yearlong course, as well as connections to other faculty in the SEA network. Undergraduates taking part in the courses become bacteriophage “hunters,” sampling their local environments for novel bacteriophage species. In the first semester, students isolate, characterize, and purify phages, completing a preliminary characterization of the phages’ DNA before sending it to the sequencing center. The following semester, students annotate their phages’ DNA sequences and select one to submit to GenBank. They present their research to fellow students at their home institutions, and selected students give presentations at an annual SEA symposium. “The program has shown that freshmen can be engaged in real research that is moving science forward,” Jordan says. Because resources are limited, she says, NRGI replaced the one-on-one apprenticeship model with peer mentoring, where individual students assist entire classes. Many institutions use graduate student mentors, but at results, Mageeney provided the other key element. “Katie went beyond the call of duty,” Dunbar says. She was there for the students, available around the clock, both in person and through e-mail. Mageeney was not only an accomplished science student but also a resident assistant and athlete, and this, according to Harrison, inspired the students under her mentorship. “They loved Katie,” Harrison adds, “they clearly trusted her and felt more comfortable going to her rather than to their teachers.” Dunbar and Harrison now realize the influence that having a great peer mentor has on the success of their program. But finding another Mageeney may be easier said than done. “It’s not simply putting an undergraduate student in the room with the freshmen,” Dunbar says. He and Harrison plan to outline the qualities necessary to identify future peer mentors for their course, and they hope to pay their peer mentor next time to compensate for the time commitment. That will require additional support from their institution. Cabrini College’s example illustrates that, when the right elements are in place, undergraduate research can be transformative for the students. Assessment data across NGRI institutions show similar impacts, Jordan says, both on retention and performance, even in at-risk student populations. The SEA is building the case for administrative support for undergraduate research at all institutions. “We are trying to open the eyes of some of the administrators,” she says, while she allows that this will be a significant paradigm shift.

The HHMI National Genomics Research Initiative at Western Kentucky University

Background Western Kentucky University is a member of a select group of colleges and universities chosen to participate in a national science experiment designed to improve undergraduate science education. To introduce freshman students to authentic research, the Howard Hughes Medical Institute’s Science Education Alliance (HHMI SEA) has implemented an innovative program to introduce genomics into the classroom. The program draws on themes and techniques from biology, microbiology, molecular biology, genomics and bioinformatics. The WKU course is called “Genome Discovery and Exploration” (GDE); WKU Genome Discovery and Exploration Program [http://bioweb.wku.edu/asp/wkungri/]. During the fall semester, students isolate bacterial viruses from the environment and characterize them using a variety of techniques including DNA analysis and electron microscopy. Over the winter break, the complete DNA sequence of one of the viruses isolated by the GDE students is determined. During the spring semester, GDE students learn how use computer programs (e.g. Consed, Glimmer, Genemark, BLAST and Phamerator) to identify all the viral genes and to make genome wide comparisons to identify evolutionary relationships. All course participants and the SEA staff are connected via the internet to share and analyze data, troubleshoot, and discuss results. Near the end of the spring semester, HHMI hosts a research symposium for course faculty and one student from each institution to report on their discoveries and experiences. As unique phages are characterized on campuses nationwide, students will have the opportunity to publish their research for the broader scientific community. This hands-on experience with the tools of Bioinformatics is an outstanding training opportunity and this unique program has helped the WKU Biology Department create an introductory pipeline to research experiences that complements our existing and planned instructional programs and allows freshman to engage in the thrill of discovery.

Vision and Change in Biology Undergraduate Education, A Call for Action—Initial Responses

The executive summary provides an overview of some of V&C's key recommendations regarding next steps in the effort to mobilize the biology community. It is, in essence, a call for national service. A publication discussing these recommendations and action items in more depth will be available later this year. Meanwhile, we highly recommend reading the Executive Summary of V&C, the NAS report (NAS, 2010), and a seminal article by Labov et al. (2010) summarizing the synergy created by these several reports on the changing nature of studies in biology and concomitant need to change biology education. Then, take action! Our hope is to see the formation of a community of biologists, similar to that forming in geology (Manduca et al., 2010): one that will advance biology undergraduate education so it truly reflects the discipline it serves.

In the NEWS A QUICK ROUNDUP OF NEWS AND INFORMATION FROM OUR COMMUNITY

In the NEWS A QUICK ROUNDUP OF NEWS AND INFORMATION FROM OUR COMMUNITY