EMBO Reports VOL 9 | NO 3 | 2008 ©2008 European Molecular Biology Organization Viewpoint Science & Society

viewpointviewpoint Hedgehogs, humans and high-school science

The benefits of involving high-school students in university research Giulio Pavesi, Antonio Siccardi, Giovanna Viale, Cinzia Grazioli, Tiziana Calciolari, Maria Luisa Tenchini & Paolo Plevani

he ‘Lisbon strategy’, adopted by between schools and universities or In Italy, the current high-school biology the member states of the European research institutes. Here, we describe the curriculum is out-dated, but we suspect that TUnion (EU) in 2000, aims to make Cus-Mi-Bio (Centre University School of it might be the same in other European coun- Europe the most dynamic and competitive Milan for Bioscience Education; www. tries. The main problems for both teachers knowledge-based economy in the world cusmibio.unimi.it) project that was devel- and students are old text books, insufficient by 2010. The overall aim is to increase the oped at the University of Milano, Italy. The time to cover important topics, a lack of levels of investment that member states put project’s aim is to raise the levels of inter- practical experiments and not enough inter- into scientific research up to and beyond est and enthusiasm of high-school students est from students who often perceive biol- 3% of their Gross Domestic Product. for the life sciences, and hopefully to attract ogy to be a ‘soft science’. Teachers therefore Although this aim will certainly not be met some of them to a career in science. need to regularly update their knowledge in the expected timeframe, it is noble and and skills, and to learn new methods with important nonetheless. here are various negative percep- which to engage their students. This requires tions of science that need to be new, discovery-based curricula that act to …even if the members of the Tovercome when persuading stu- make science more appealing for students. dents that it is a worthy career choice. EU increase investment into Many high-school students still believe stablishing functional and synergistic research, it will be in vain if they that studying the natural sciences is a links between the high-school edu- do not also work to increase the hard choice compared, for example, to Ecation system—students and their number of researchers economics or the social sciences, and that teachers—and research universities is one science does not offer a rewarding career way to do this. Of course, students need a path. At least in Italy, such perceptions basic knowledge of mathematics, physics, However, even if the members of the and their consequences are well founded: chemistry and biology, but, to capture their EU increase investment into research, the number of students graduating in interest and curiosity, it is also important to it will be in vain if they do not also work mathematics, physics and chemistry is expose them to cutting-edge research and to to increase the number of researchers. often insufficient to meet the economy’s give them the opportunity to experience the Indeed, the current number of researchers demands, fellowships for PhD students excitement of working in a research labora- per 100,000 citizens in the EU is consider- are not sufficient to make a living, and tory. This, in turn, implies that the scientific ably lower than the figure for the USA or career options are often not linked to curricula in high schools must not be limited Japan. As scientists, we have virtually no scientific merits. Nonetheless, it is still to teaching the history of science, describ- possibility to influence how much money important to invest in the future of the ing the organs of our bodies or just learning our governments spend on research and research enterprise by motivating young the Linnaean classification system, but must development, but we can have a much people, and to identify those with enough embrace more practical courses. more active role in making science a more enthusiasm and curiosity to embark on a attractive career option for young people— scientific career. Such an investment into …the education system must be notably high-school students. young people will also benefit univer Various projects and initiatives in EU sities by attracting motivated and gifted able to train a new generation of countries and the USA have sought to students, and by making their transition scientists and researchers capable achieve this aim by forging closer links from high school more conscious. of using the new tools…

The three main players—high-school students, science teachers and research- Students attending “Try the BioLab” Best student Winners ers—must learn to interact with each other (~280 classes) from each class to forge links between schools and univer- 10 sities. Researchers are able to identify the most interesting and promising research topics, but they have limited amounts of 220 time in which to teach and instruct high- school students; this task is better fulfilled by the teachers, who are an equally integral part of the entire project. Their close ~6,000 cooperation eventually generates a virtu- ous circle: researchers and teachers iden- First selection step Second tify and propose scientific topics that can performed by each selection step class teacher: at Cus-Mi-Bio: be discussed in the classrooms and that Multiple-choice Computer- lead to related experiments; together they questions assisted (the same for and oral develop the theoretical and practical activ- all classes) evaluations ities that stimulate the curiosity of students, who will, in turn, urge their teachers to acquire additional knowledge. Fig 1 | Selection steps in the ‘A week as a researcher’ contest limited to talented high-school students attending BioLab activities. Numbers refer to the 2006–2007 selection. …we think that letting students ‘discover’ things—rather than just learning about many new advances in this field and the birth genetics or biotechnology. These experi- them—can greatly improve of new integrated disciplines such as bio ments include: DNA fingerprinting, identi- their understanding of the basic informatics, computational biology, imaging fication of genetically modified organisms, concepts of biology and systems biology. Therefore, the education cloning, genetic diseases, model systems system must be able to train a new generation in biology, gene hunting, and many more. of scientists and researchers capable of using ‘Try the BioLab’ is open to all high-school Such a scheme should avoid an elite- the new tools efficiently and correctly. students and, so far, more than 11,000 stu- focused approach that would select only At present, Cus-Mi-Bio has two high- dents have attended at least one of these the best students for participation in school teachers working full-time, together courses during the past three years. The most research experience. The scheme must with about two-dozen University of Milano motivated and skilled students then partici- include students of all levels to identify scientists and professors from academic fac- pate in a competition that selects 10–15 of those most interested in research. This first ulties as diverse as medicine, molecular biol- them to attend a ‘week as a researcher’ in phase must then be complemented by a ogy, agriculture, pharmacology and veterinary a national or international research labora- second phase focused on the most gifted sciences. In addition, several PhD students tory at the end of the school year (Fig 1). This and enthusiastic students. and post-docs act as tutors during the experi- contest selects talented students and helps mental work in the laboratory: their presence to maintain contact with them. ince 2004, Cus-Mi-Bio has tried strongly facilitates productive interactions and Cus-Mi-Bio also launched a new initia- to bring this scenario to life. Cus- dialogue with high-school students and helps tive at the end of 2006 called, ‘Wannabe SMi-Bio is located on the University to break down the ‘teacher–student’ barrier. a researcher: attend a top science project’. of Milano’s campus and includes a fully Cus-Mi-Bio also organizes specific This programme aims to combine pro- equipped molecular biology laboratory courses and meetings on the frontiers of fessional research with research-based and bioinformatics facilities to host 70 stu- modern biology for high-school teachers undergraduate education and is limited dents at individual workstations. Clearly, to provide them with up-to-date scientific to the 10 winners of the contest and 30 only a limited number of high schools have knowledge. So far, more than 300 teach- other students who are close runners in the the facilities to carry out research activities ers have taken part in these initiatives and contest. The aim is to develop further their themselves, even in Milano, the capital of these working groups also produce hand- predisposition for science and research the most economically developed region in books, experiments, and ‘tools and tips’ by having them contribute to a research Italy. The Cus-Mi-Bio laboratories are there- that teachers can use in their classes. project throughout the entire school year, fore an integral part of the Lombardy school in part at Cus-Mi-Bio and in part on their system—indeed, the University of Milano he main activity organized by Cus- own computers at home. and the Lombardy Education Office jointly Mi-Bio for high-school students is finance the laboratory’s activities. Tthe so-called ‘Try the BioLab’. Every he 2006–2007 project was called Cus-Mi-Bio initiatives are so far limited school day, one or two classes perform ‘Following the footsteps of evolu- to the biosciences. Nonetheless, they are experiments in the two Cus-Mi-Bio labora- Ttion, looking for new genes’, and well-timed because the past decade has seen tories on topics drawn from the fields of was based on a bioinformatics analysis of

results correspond to regions where exons Sidebar A | Participants in the ‘Wannabe a researcher?’ programme by Cus-Mi-Bio of two other genes are wittily annotated as The high-school ‘Wannabe a researcher?’ students attending the 2007 project were: Gangai Alessandra ‘two more hedgehogs’. (Liceo Volta, Milano); Carlini Valentina, Ferrante Giulia, Fortunato Federica, Magni Martina, Massari Lucia (Liceo Donatelli-Pascal, Milano); Andreosso Ivan (Liceo Vittorio Veneto, Milano); Caspani Anna, At this point, we asked the students to Citterio Simone, Lippi Laura, Rabboni Francesca, Rossini Giulia, Sala Giulia, Saturno Elisa (Liceo align the human SHH protein against the Don Gnocchi, Carate Brianza, Milano); Brambilla Marta, Moretti Luca, Poletti Davide (Liceo Banfi, mouse genome. Again, they obtained dif- Vimercate, Milano); Erasmi Fulvia (Liceo Vico, Corsico, Milano); Branca Luca, Brindisi Pietro, Sutera ferent ‘hits’ and discovered three regions— Samuele (Istituto Tecnico Agrario Mendel-Villa Cortese, Legnano, Milano); Cappelletti Alessandro, corresponding to genes annotated on the Greco Benedetta (Liceo Novello, Codogno, Lodi); Airaghi Giulia, Bizzarro Francesca, Borroni Manuel, mouse genome—which encode amino-acid Gilli Marta, Lucchetti Michele, Montanari Maria Giulia, Pescatori Claudia, Restelli Enrico (Liceo Legnani, sequences similar to human SHH. By repeat- Saronno, Varese); Mason Emanuele, Mocchetti Federico, Poggi Nicolò, Scorti Andrea (Liceo Tosi, Busto ing the same exercise with Drosophila, the Arsizio, Varese); Castelli Matteo (Liceo Volta, Como); Brusa Filippo, Msiyah Fatim Zuhra (Istituto students were again able to find a single Tecnico-Industriale Tessile Carcano, Como). region located within an annotated exon. At this point, we asked the students to speculate why there are similar gene sequences in different species. They were then able to con- the human genome with the aim of dis- It immediately catches the students’ atten- tinue the searches alone—repeating the same covering new genes. Bioinformatics and tion owing to its name and to the fact that, steps with different human proteins and/or molecular evolution are rarely taught in by clicking around and browsing through with different species—in order to answer high-school curricula and the project was the annotations, they can discover the pic- questions such as: how many hedgehogs therefore exciting for both the students and ture of the cartoon character after which it does it take to make a pufferfish? The fact that their teachers. In fact, genomic browsers was named. Although the gene has a sim- exercises of this kind only require a computer and bioinformatics tools allow the observa- ple structure of three exons, it summarizes with internet access makes them an endless tion—even in an abstract representation— almost every aspect of alternative transcrip- source of possible home projects. of genes and gene transcription, and thus tion and splicing—alternative transcription provide an extremely powerful tool to teach initiation and termination, cassette exons, Today’s students are the the basics of modern molecular biology. retained introns, and alternative 5'- and While we familiarized the students with 3'-ends—all of which are easily visible by voters and decision-makers of the bioinformatics tools they were going to aligning different mRNAs to the genome. tomorrow, and it is essential use, we also brushed up their knowledge of that we give them the best molecular biology and told them about the nother typical exercise consisted possible means to form their own latest discoveries in the field. of providing students with one or opinions and ideas The students in the ‘Wannabe a Amore transcript sequences and researcher’ programme (Sidebar A) were asking them questions such as: where is presented with the basic concepts of the gene that produced the sequence(s) Once the students had discovered these gene expression (i.e. transcription, splic- located in the genome and on which strand, genomic similarities, we asked them why ing and translation), but instead of looking and which alternative splicing events, if a fly has a gene that can also be found in at schematic drawings on a blackboard, any, can you find? The experiment can be humans, and why the human genome they had direct access to genomic data replayed by using protein sequences and has multiple copies of a gene. This auto and annotations through the UCSC (http:// asking the students to locate the gene that matically required us to explain concepts genome.ucsc.edu) and ENSEMBL (www. encodes for a given amino-acid sequence such as homology, orthology, paralogy and ensembl.org) genomic browsers. The UCSC or, alternatively, to predict the amino-acid synteny, as well as evolutionary mecha- browser was used because it offers basic sequence of a mRNA sequence—thus nisms, including genome rearrangements and intuitive tools to perform simple ‘experi- making them more familiar with 5'- and and duplications. Every concept is eas- ments’ without the need to delve into bio- 3'-untranslated regions, amino-acid codons, ily visible within the genome browser— informatics or statistical details. Also, it and start and stop codons. for example, by examining alignments is possible to hide confusing annotations An additional advantage of these activi- and conservation between genomes. in the browser and leave only the relevant ties is that transcript and protein alignments Bioinformatics provides teachers with end- information on the screen. against the genome do not always give less opportunities to teach modern biol- The students could observe gene struc- unique results—that is, significant sequence ogy—for example, a microRNA sequence ture, transcription and splicing by looking similarities can be found in other genomic mapped onto the genome might lead to a at the annotations of genes—that is, images regions. For example, by aligning the SHH discussion of RNA interference. that show the alignment of transcripts to RefSeq protein against the human genome, Furthermore, genomics also gives rise the genomic sequence, and the way they three results are obtained that can be inter- to interesting questions: how many genes are split into exons and introns. These preted as: the human genome contains one does it take to make a human? Why do provide an immediate view of alternative region that encodes for the SHH protein, humans, mice and all mammals have vir- splicing mechanisms to produce different but two more regions seem to encode for an tually the ‘same’ genes—that is, why can mRNAs. In our classes, we used the human amino-acid sequence that is similar to SHH. their proteins be mapped easily onto each sonic hedgehog homologue (SHH ) gene. Even more interesting is that the other two other’s genomes? Why do plants usually

Chr10: 55235000 55240000 55245000 55250000 Human–mouse conserved regions_ENr114 ENr114_track UCSC gene predictions based on RefSeq, UniProt, GenBank and Comparative Genomics PCDH15 PCDH15 RefSeq Genes PCDH15 Human mRNAs from GenBank AK311240 AK126923 Human ESTs that have been spliced CF457420 Vertebrate Multiz Alignment & PhastCons Conservation (28 Species)

Mammal constructs

Rhesus Mouse Dog Horse Armadillo Opossum Platypus Lizard Chicken X_tropicalis Stickleback Single nucleotide polymorphisms (dbSNP build 126) SNPs (126) Repeating elements by RepeatMasker RepeatMasker Encyclopedia of DNA elements (ENCODE) regions ENr114

Fig 2 | A putative ‘new gene’ discovered by one of the students attending the programme. EST, expressed sequence tags; SNP, single nucleotide polymorphism.

have more genes than mammals, and why on the ENCODE project (www.genome.gov) stir public debate and controversy. Today’s is it that the number of genes in a simple could contain a new protein-encoding students are the voters and decision-makers organism, such as Caenorhabditis elegans, gene—or at least a new exon. Although the of tomorrow, and it is essential that we give compared with that in a complex organism, ENCODE regions are now thoroughly analy them the best possible means to form their such as Homo sapiens, is not that different? sed, the students were able to identify at own opinions and ideas. These questions, in turn, help us to intro- least three possible new protein-encoding duce the latest discoveries in molecular genes (Fig 2), and a large number of new ACKNOWLEDGEMENTS biology, such as the concept of alternative as-yet-unannotated exons. We thank the Università degli Studi di Milano splicing, gene expression modulation or Overall, our experience with the Cus-Mi- and the Direzione Regionale Scolastica della Lombardia for financial support. We also genetic diseases caused by ‘errors’ in these Bio students shows that sequencing projects acknowledge the help of several enthusiastic mechanisms. and bioinformatics are not only great tools high-school science teachers, their students, for research, but also for teaching the con- and all our colleagues and graduate students nce this crash-course in modern cepts that underlie molecular biology and participating at the Cus-Mi-Bio activities. molecular biology and evolu- evolution. Regardless of the tools used and Otion was completed, our students the examples chosen, we think that letting finally started their real research project: students ‘discover’ things—rather than just Giulio Pavesi, Antonio Siccardi, Maria Luisa to find out whether a likely protein- learning about them—can greatly improve Tenchini, Giovanna Viale and Paolo Plevani are at coding gene could actually be ‘missing’ in their understanding of the basic concepts of the Università degli Studi di Milano, Italy; the sense that it might not be annotated in biology. For example, we did not present evo- Cinzia Grazioli is at the Liceo Scientifico Vittorio the available RefSeq gene annotations of the lution as dogma, but rather let our students Veneto, Milano, Italy;Tiziana Calciolari is at the Liceo Scientifico Albert Einstein, Milano, Italy. human genome. The students were split into investigate and discover several ‘footprints’ of All authors participate in the Cus-Mi-Bio. small groups and each group was assigned a evolution. We believe that getting such first- E-mail: [email protected]; different part of the human genome. In par- hand experience of evolution and molecular [email protected] ticular, the task was to assess whether a pre- biology is extremely important, especially selected region of the human genome based when discoveries from the life sciences often doi:10.1038/embor.2008.25