Bringing life into biology lessons: using the fruit fly Drosophila as a powerful modern teaching tool

Introduction

In biomedical research, small model organisms such as the fruit fly Drosophila melanogaster are important pillars in the process of scientific discovery. For 27 years, I have been using Drosophila as my organism of choice and the essential discovery tool to study fundamental principles of the nervous system (LINK1 and LINK2). For more than 6 years, together with my colleague Sanjai Patel and other members of the Manchester Fly Facility, I have been actively engaging in science communication to raise public awareness of the importance of fly research, with a strong focus on school activities (see further explanations here). From this, we realised the enormous potential that Drosophila has beyond research also for biology teaching. It is a powerful modern teaching tool not only for classical Genetics but for many curriculum-relevant areas of biology, providing unique access to informative, inspiring and memorable classroom experiments. As is explained in our recent school journal article and the 1^st movie below, we now collaborate with teachers and schools on the droso4schools project, to capitalise on the advantages of Drosophila and develop freely available sample lessons with adjunct materials (e.g. teacher notes, risk assessments, homework tasks, exercises, experiment instructions), and a dedicated website (LINK) providing many helpful online resources. Furthermore see our repository with downloadable resources for extracurricular school visits (LINK).

Why is Drosophila so important for biomedical research?

Naturally, students want to know why flies are used to learn biology. The explanation is made easy with our two “Small fly, big impact” movies (see the two movies below), which were tested in schools with great success. Furthermore, there is a dedicated school article explaining our own research using Drosophila (LINK), and a dedicated tab on our droso4schools website provides further background information (LINK). In a nutshell, the films and website explain…

• …that it was serendipity which brought flies into genetic research a hundred years ago,
• …that it were the many practical advantages and cost-effectiveness of Drosophila which made it so popular for studying the function and biology behind genes, and
• …that it is the astonishingly high degree of evolutionary conservation from flies to humans that makes understanding of biology in flies so relevant for biomedical research even into human disease, having led to five Nobel prizes in Physiology and Medicine so far.

Why is Drosophila so useful in biology classes?

“I am a drosophilist”: students at Trinity CoE High (one of the schools we collaborate with) like the fly!

As will become clear from the sample lessons explained in the next section, there are two important advantages for using Drosophila in classrooms, in particular (1) the breadth and depth of conceptual understanding of biology in the fly, and (2) the fact that flies are uniquely suited for live experiments in schools.

• 

  Flies are kept in small vials with a bit of food at the bottom: ideal for maintaining them even in schools.

  Conceptual understanding: A century of cutting edge research has turned Drosophila into the conceptually best understood animal model organism that we have to date. It has not only taught us about how genes are organised on chromosomes and the rules of inheritance, but also fundamental concepts of development, nervous system function, the immune system, our biological clock and jet lag, evolution and population genetics, the genetics of learning, principles of stem cells, and even mechanisms of disease including cancer and neurodegeneration (see Resource 2b “Why the fly?“). But how does this help in classrooms?

  • The breadth of biology topics investigated in flies provides potential teaching materials for a wide range of curriculum-relevant biology specifications, ranging from classical genetics to gene technology, gene expression, enzymes, neurobiology and even evolution and behaviour.
  • The sheer volume of knowledge in each of those areas provides a plethora of examples, experiments, anecdotes and facts that can be used to illustrate and make lessons more engaging and entertaining.
  • The depth and detail of conceptual understanding in flies facilitates teaching, based on the simple rationale that teaching is the easier the better the contents are understood.

• Live experiments: It is straightforward, cheap and ethically unproblematic to use and breed flies in schools, and there are many simple experiments that can be performed (see our sample lessons in the next section). This brings living animals into classrooms which, combined with experiments that reflect relevant contemporary research, tends to leave long-lasting experiences. I frequently talk to people who were taught classical genetics with flies decades ago and still hold positive memories.

The breadth of scientific studies in flies reaches across and contributes to a wide range of important topics in biomedical research.

Examples of biology contents that can be taught with flies

There are many ways in which flies can be used as teaching tools in schools. Here we will give some examples for which resources are either provided online already or can be made available upon request.

(1) Life cycle in primary schools

The Drosophila life cycle animated and made attractive for primary school pupils. Click to enlarge

Teaching the life cycle in primary schools is often done using metamorphosis of tadpoles into frogs or of caterpillars into butterflies, but experiencing these examples in real time can only be done during a certain period of the year and takes many weeks. With flies this can be done in one day since all life forms are available at any time, and the whole life cycle can be experienced in real time during less than two weeks (see image below and this LINK). We recently taught life cycle to 10 year olds in primary school with great success. During the lesson, we compared frog and dragon fly, explained the short adult life span of mayflies (showing a film), introduced the concept of complete metamorphosis (accompanied by an activity sheet where children learned which insect groups have a pupal stage), introduced to Drosophila (with the microscope fly activity from section 6 and the “Why the fly?” film), used examples from Drosophila to explain what happens during metamorphosis in the pupa, and eventually explained life cycles of Plasmodium in Malaria and of flatworms in different diseases (making clear why to wash hands after playing outside!). These resources will be made available online, but will be sent out to you upon request.

(2) Drosophila and computer programming

The first version of the scratch computer game based on the Drosophila life cycle. Click to play!

In ICT classes, the Scratch program has become a sensible and powerful way to introduce students to the logic of computer programming, and Scratch tempts to be taken on as a hobby at home. To engage on this path, we have published a Scratch-based computer game (see below and LINK) which uses the funny cartoons of the Drosophila life cycle as the basis, and the maintenance of fly stocks against the odds of genetic mutations, parasite infestation and bacterial/viral infections as the story line. Since all programming code in Scratch is open, this game can be modified or developed further. For this, all the used figures (“sprites”) have been made available for download (LINK). Beyond this, we envisage that easy behavioural experiments in Drosophila offer ways to generate biological data that could be analysed using more advanced and well supported programming languages like Python and the cheap computing power made available through Raspberry Pis (LINK).

(3) Principal functions of our organs

The physiological requirements for life are so fundamental that most of our organs have common evolutionary roots. An active and effective way to learn about our organs is therefore through exploring their commonalities with organs of other organisms. This strategy can capitalise on the vast knowledge that we have about the tissues and organs of Drosophila. To facilitate this, we provide a dedicated webpage describing the structures and fundamental functions of our organs in direct comparison to those of the fruit fly (Resource 1c).

Most human organs have a match in flies with shared evolutionary roots, ideal to compare and understand the fundamental requirements of these organs.

(4) The genetics of alcohol metabolism

Combining the gene to protein concept, principles of enzymes, genetic variation and concepts of Evolution.

This lesson is fully developed, was tested with eighty Year 13 students (one high achievers class, two mixed ability classes, one support class), a PowerPoint file with adjoint materials is available online (Resource 1a, e, 3b) and a dedicated webpage is available to support revision and homework tasks (Resource 1e). It is an excellent synoptic, end-of-year lesson which establishes conceptual links between at least seven curriculum-relevant biology specifications. These include fermentation, the gene to protein concept, enzyme function, pharmacology and associative learning, genetic variation, and principles of evolution. Students dissect normal and alcohol dehydrogenase deficient fly maggots and use a colour reaction to assess the maggots’ ability to metabolise alcohol. They observe the effects of alcohol consumption on normal and mutant flies, and they compare different alleles of the Adh gene by translating their DNA code into RNA and protein. This lesson offers excellent opportunities to achieve differentiation and to discuss the social relevance of alcohol and alcohol abuse.

A simple 5-10 minute colour reaction experiment demonstrating the genetics of enzyme activity. Click for detailed explanations.

(5) Applying statistics to performance tests of young versus ageing flies

Neurodegenerative diseases (ND) destroy nerve cells which form the cables that wire our bodies. Some ND primarily affect nerve cells required for body movement, as illustrated here.

Learning to draw graphs and use spread sheets using data obtained with living flies in the classroom.

This lesson is also available as a resource online accompanied by 5 dedicated webpages (Resource 1a, d, 3a). It was tested on sixty Year 9 pupils. It uses a low-cost, easy to set-up experiment known as the “climbing test”: two groups of flies (one week old teenagers versus five week old seniors) are tapped down in two parallel vials and are given 15 seconds to climb back up, at which point a picture is taken. Students then determine how far the ten individual flies in each vial have climbed on a scale of 0 to 10, usually finding that the young flies show much better motor-performance. This is then used to draw graphs, understand the importance of sample numbers and learn to apply statistics. To illustrate relevance, concepts of ageing and neurodegeneration are introduced accompanied by activity sheets, and examples are provided on how the climbing assay is used during ageing and neurodegeneration research on flies.

(6) Classical genetics

An easy to monitor experiment with classical genetic markers. All kids love it!

This lesson is not yet available online, but will be sent out upon request. During this lesson, students learn about classical genetics and the practical uses of marker mutations as they are applied in contemporary research laboratories (including Punnett squares). For this, excellent low cost dissection microscopes can be used (see Resource 2c “Outreach Resources“), and we developed simple activities where student success in identifying markers is easy to monitor. Furthermore, the lesson provides an insight into the process of scientific discovery (how it was found that genes lie on chromosomes), and how this helps understanding biological phenomena in humans, such as male predisposition to colour blindness. Where transgenic flies are permitted on school grounds, modern genetic markers can also be used, in particular fly strains containing green fluorescent proteins. Using a simple hand-held fluorescent lamp with integrated camera (see Resource 2c “Outreach Resources“), gleaming organs can be observed live in these maggots.

Students performing the genetic marker exercise.

(7) Fundamental principles of the nervous system

Comparing electrical versus chemical synapses and understanding them in the context of a simple neuronal circuit.

This lesson is not yet up as a resources, although some explanations of its content can already be seen under the “L3-Neurons” tab on the droso4schools site. It starts with a simple request: “Decide to bend or stretch your arm! What happens in your body?”. This simple example forms a powerful story line which introduces to the wiring principles of the nervous system, nerve impulses (action potentials), and the working of synapses. For example, our “5 steps to an action potential” strategy is enormously successful with students already at GCSE stage. The lesson further illustrates the concepts and their application by explaining spinal cord injury and epilepsy, illustrated by shaking epileptic flies into seizure. It illustrates the power of synapses with a little experiment where flies are paralysed through warming them up to body temperature, introducing also to cutting edge technologies and strategies used to study the nervous system. Where transgenic flies are permitted on school grounds, we have simple experiments for the use of state-of-the-art opto- or thermo-genetics (using light or temperature to manipulate nerve cells and fly behaviours; see this TED talk).

A simple animation explaining a nerve impulse (action potential). Click for detailed explanations.

Further ideas or requests?

Many more curriculum-relevant topics can be taught using Drosophila as a modern teaching tool, and we are curious to hear which ones would be of interest to you. We are keen to collaborate with you to implement such lessons. Feel free to contact us: Andreas.Prokop@manchester.ac.uk and Sanjai.Patel@manchester.ac.uk.

Summary table of helpful resources

• The droso4schools website provides relevant information:
  • an overview of the project and of available sample lessons;
  • the “Why fly?” page explains the advantages of Drosophila in research;
  • the “Organs” page compares tissues and organs of flies and humans with helpful overview images.
  • the “L1-Climbing Assay” tab provides 5 pages of information supporting the motorskills experiment: (1) a description of the experiment, (2) background information on neurodegenerative diseases and ageing, (3) information of how flies are used to study these conditions, (4) a glossary of relevant terms, and (5) explanations of relevant statistics;
  • the “L2-Alcohol” provides background information for the lesson on alcohol, covering fermentation, principles of enzymes, drug treatment of alcohol addiction, natural variation of alcohol tolerance and their genetic basis, the geographical distribution of variations and their evolutionary basis
  • the “L3-Neurons” tab is half populated and contains background information on the nervous system lecture which will be uploaded soon.
• Our school journal articles
  • Harbottle, J., Strangward, P., Alnuamaani, C., Lawes, S., Patel, S., Prokop, A. (2016). Making research fly in schools: Drosophila as a powerful modern tool for teaching Biology. School Science Review 97, 19-23 — [LINK]
  • Prokop, A. (2016). Fruit flies in biological research. Biological Sciences Review 28, 10-14 — [LINK]
• “For the Public” area of the Manchester Fly Facility website
  • the “Why the fly?” page complements the information on droso4schools through listing simple facts and over 80 lay articles about fly research;
  • the “Teachers & Schools” page explains the rationale for our school work and lists the services we provide for schools to support fly lessons, as well as our past/future school events;
  • the “Outreach Resources” page lists about 100 links to information and resources that can be useful for outreach work and teaching at school and university levels.
• The figshare.com resource site for download of sample lessons and adjoined resource materials
  • zip file containing the L1-Climbing Test lesson
  • zip file containing the L2-Alcohol lesson
• Manchester Fly Facility YouTube channel
  • two educational “Small fly, big impact” movies describing the origins and importance of fly research (part 1 – “Why the fly?”) and how research in flies can help to understand disease and find potential treatments (part 2 – “Making research fly”)
  • a film explaining the droso4school project through interviews with all involved

This blog was first published as a guest blog on the pedagoo.org site.

Maintaining a strong Drosophila community — starting with students

More than a century of intense research with the fruit fly Drosophila has arguably turned this little insect into the animal whose biology we understand the most. Work with Drosophila has had a seminal impact on the development of modern biology [1, 2]. Flies offer many practical advantages (see more here), and fly researchers capitalize on a well-organized community, a rich pool of molecular, genetic, and online tools, as well as technologies that tend to be at the forefront of the field. As Hugo Bellen nicely sums it up: “You get 10 times more biology for a dollar invested in flies than you get in mice” [LINK]. There is some evidence, however, that there has been a downturn in NIH and NSF funding for Drosophila research [3]. One explanation for this could be the worldwide political trend of reducing funding for basic science in favor of providing funds for more translational research — in an (arguably false) expectation of short-term returns on tax investments. Unfortunately, this strategy ignores the role fundamental biology plays as the lifeblood for translational research. A trend of decreased support for basic science may well have the opposite of its intended effect, gradually and eventually drying up the production line that feeds advances in biomedical application. What can fly researchers do to address these issues? I would argue that education, science communication, and outreach initiatives are some of the most critical tools we have for maintaining a robust Drosophila community that can continue its important contributions to biology and biomedical research. In this blog post, I describe some existing outreach initiatives, and discuss what more we can do. A more detailed explanation of rationales, strategies and resources has been described in a recent publication [4].

An increasing need for science communication and outreach

Ironically, despite the threat of decreased funding, Drosophila research is needed more urgently than ever, as “omics” approaches in human genetics release a flood of disease-linked genes — which are more often black boxes than known entities. Established model organisms like Drosophila will be key to understanding these genes and testing hypotheses about them quickly and efficiently. Fruit flies are also powerful tools for facing other challenges generated by “omics” data and new technologies. The fly’s efficient combinatorial genetics are ideal for validating and understanding gene networks suggested, and Drosophila can readily serve as an experimental pipeline to help iteratively build and test computational models [e.g. 5] While flies are clearly not mini-humans, and there are limitations to using Drosophila for studying human diseases, Drosophila has a proven strength in pioneering research into unknown territories. Using efficient and cost-effective research in flies to explore these genes is a responsible and low-risk investment, and countless cases from the last decades have shown us that this investment pays off: knowledge gained in flies frequently inspires and enormously accelerates advances in mammalian and human research. This has been well documented in the article by Hugo Bellen and colleagues: “100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future” [6]. Does the community of drosophilists do enough to communicate these benefits of fly research to the general public, including politicians? We tend to be so occupied with our scientific activities that public communication of our work is easily overlooked (or intentionally sidestepped). At the outreach workshop of the last GSA Annual Drosophila Research Conference in Chicago, Allan Spradling also commented that fewer members of the public, especially the younger generations, seem to have encountered Drosophila in schools. I observe the same at museum events, where those who were taught about flies at school even decades ago, tend to respond with noticeably greater curiosity and interest about fly-related topics than those without such memories. Traditionally, flies were used in school lessons to teach classical Genetics, but the enthusiasm for this strategy seems to have been widely lost. As a consequence, I notice that first year university students often have little appreciation of, and even a disregard for the usefulness of invertebrate model organisms. We can hardly blame them for this. On occasion, I wonder whether even our fellow scientists and clinicians are sufficiently aware of the opportunities fly research offers. Clearly, science has moved on. Drosophila was once unrivalled in its status as a “boundary object”, i.e. a model in which genetic strategies could be used for the investigation of biological mechanism (for an enlightening article on Drosophila embryos as boundary objects, see [7]). But as the genetic methods for other organisms have substantially improved over the years, Drosophila now shares this key role with other important models (and even culture systems). The advent of CRISPR technology will further contribute to this trend. Arguments for supporting fly research are therefore less black-and-white than in the past, and need to be substantially refined. We need to creatively, but sensibly, highlight the speed, efficiency and cost-effectiveness of our research, as well as the depth of conceptual understanding, the high degree of genetic and mechanistic conservation, and the unique opportunities for newly arising research directions.

What can be done to address these issues?

Scientists and educators can do more to promote the public understanding and appreciation of invertebrate model organisms, including Drosophila. Ideally, such outreach initiatives should be:

• multi-faceted, targeting audiences at all levels;

• follow long-term strategic plans, and;

• be well coordinated amongst drosophilists.

Initiatives that address the first two aspects are starting to spread within the Drosophila community:

• More than a decade ago Christian Klämbt started the visionary “FlyMove” project, a website dedicated to illustrating and explaining Drosophila developmental biology in simple terms, aimed at university students and teachers.

• Increasing numbers of school or university lessons are being published, as well as ideas for science fair displays [LINK].

• Bethany Christmann‘s blog “Fly on the wall” is an outstanding initiative to explain in lay terms trends in Drosophila.

• Originating from her participation in a 2011 workshop on Drosophila Neurogenetics (organised by Lucia Prieto-Godino and Sadiq Yusuf in Uganda), Isabel Palacios runs an increasingly successful series of Drosophila workshops in Africa. Together, with the development of the TReND in Africa organization which developed from the same workshop [LINK1; LINK2; LINK3], these initiatives are successfully seeding an African biomedical research community which also capitalizes on Drosophila as an affordable model organism.

The Manchester Fly Facility has also developed a range of outreach activities and resources:

• Two entertaining films about Drosophila “Small fly, big impact” (part 1 & part 2), which have proven popular and valuable online and in schools.

• Free-for-download lesson plans and the droso4schools support website, which grew from an initiative to establish flies as modern teaching tools at schools [LINK1; LINK2].

• Thoroughly tested approaches for multi-stand science fair displays; for example a successful neurobiology fair where Drosophila researchers joined ranks with mammalian neurobiologists and neurosurgeons.

• Novelties for engaging young children, such as Hama bead patterns. These can also be used for science fair flyers children can take home, ideal for using a “Trojan horse strategy” [8], in which we provide web links to lay resources on Drosophila that parents can investigate.

• The twitterbot “@fly_papers“, set up by Casey Bergman to provide an easy means to stay up-to-date with the fly literature [9]. This information pipeline has recently been joined by Thomas Brody‘s new twitter feed “@interactivefly“.

• The Drosophila genetics training package [10] including the “Rough guide to Drosophila mating schemes” [11], developed for training newcomers to fly research, is now being used worldwide.

• Strategies to implement this training package in university courses, including flexible methods to electronically assess learned skills (see below).

Unfortunately, the third aspect, i.e. coordinating outreach activities within the Drosophila community, is presently difficult to achieve, and, as a community, we need to develop better means of communication. The visionary idea of the Drosophila Information Service to spread the word within the community and share good practice [12] needs to be translated into modern communication technologies, which can be as simple as a moderated newsfeed. Another strategy is to increase the visibility of existing materials. To this end, the Manchester Fly Facility has developed a website, complementary to FlyBase and The Interactive Fly, which provides a one-stop-shop for Drosophila science communication resources, also including growing lists of lay articles and material about the history of Drosophila research.

Long-term strategies: Targeting students

For our efforts to have profound effect, we need long-term strategies. One such strategy is to give flies a stronger prominence in biology school curricula. This strategy also has a lot to offer to schools. Flies provide exceptionally good conceptual understanding of biology and bring countless opportunities for exciting, low budget experiments with live animals that reflect contemporary research (see the droso4schools website). Another long-term strategy is to increase Drosophila teaching of university students. This audience is unique because they are non-expert members of the general public but are also potential future scientists. For example, to address the “general public” side of students, we can adapt the Drosophila resources developed for schools. In my experience, starting at this fundamental level is a good way to engage university students. To address “future scientists,” the fly genetics training package we described in G3 [10] offers great opportunities. Originally, this training was developed for use in Drosophila research groups, to teach the fundamentals of classical Genetics and transgenics, as well as their application during mating scheme design. As explained in our more recent G3 paper [12], applying this training to university courses has a number of important advantages, including:

• Introducing students to the core strategies and concepts of genetic model organisms like Drosophila.

• Reflecting relevant training that students can directly apply if they choose to join a lab working with flies or other genetic model organisms.

• Improved learning by teaching the fundamental concepts of classical genetics in an integrated and applied way.

• providing training in strategic thinking and representing active learning at higher order, both desirable goals in university education.

• Flexibility; It can be used either as a stand-alone unit or integrated into courses on other subjects, including Genetics. Incorporating the module into genetics courses provides a potent means to address critical comments by Rosemary J. Redfield, who pointed out a need to change the focus of genetics courses away from classical topics and towards state-of-the-art molecular, genomics, and “omics” approaches [14]. Embedding the Drosophila training module in a Genetics course alongside other modern techniques will ensure that basic classical genetics is taught in an efficient way that leaves space for other topics. The feasibility of this approach is demonstrated by our annual developmental genetics course at Manchester, where the fly genetics training has been successfully integrated [15].

This developmental genetics course includes up to 65 students. Assessing such large numbers for mating scheme design skills is not trivial. To make assessment more feasible, we developed a hybrid strategy, in which students solve a mating scheme task first on paper, and the solution is then queried using standard multiple-choice or multiple answer e-assessment questions. As explained in our G3 paper [13], this method combines the advantages of paper-based and electronic assessments, so that exams are more fair, and provide the flexibility to assess a wide range of knowledge and skills, including virtually every aspect of mating scheme design and the underlying classical Genetics, as well as the ability to translate between genotypic and phenotypic levels. As we point out, this strategy is not only suitable for genetics, but could as well be applied other disciplines requiring complex problem solving, such as mathematics, chemistry, physics or informatics. We used this assessment in three consecutive years, and have observed a reliable and realistic spread of marks that clearly highlights the stronger candidates. We are therefore confident that in-place strategies can be used to teach and assess Drosophila mating scheme design even to large cohorts of university students. Since the strategy is based on an interactive, interesting and unconventional method that engages students, it hopefully leads to a long-lasting and better appreciation of the usefulness of model organisms.

Conclusion

Drosophila plays a key role in the current research landscape, and there are many areas in which the fly can make major contributions in the future. But there are alarming signs that funding trends might not favor invertebrate model organisms. Better communication and active outreach is urgently required to address this trend, ideally making use of long-term strategies. Here, I have tried to provide an overview of the ways in which this can be achieved, hopefully inspiring more researchers to join in. As I have argued in an another blog post and recent publication [4] scientists themselves can learn a lot from engaging with the public. In my own experience, outreach has helped enormously in developing better arguments and ways to communicate my research, and this has turned out to be extremely useful for grant applications and publications — all in all, a win-win situation!

Acknowledgements

I am most grateful to Cristy Gelling for inspiring me to write this blog, and would like to thank Cristy and the GSA team for very helpful comments and editorial suggestions. This blog will be published in parallel on the GSA blog site.

References

[1]    Kohler, 1994, Lords of the fly. Drosophila genetics and the experimental life, Univ Chicago Press
[2]    Brookes, 2001/2002, Fly: The Unsung Hero of Twentieth-Century Science, Ecco/Phoenix
[3]    Wangler et al., 2015, Genetics 199, 639ff
[4]   Patel & Prokop, 2015, bioRxiv 10.1101/023838, ff.
[5]    Shimizu et al., 2014, Cell 157, 1160ff
[6]    Bellen et al., 2010, Nat Rev Neurosci 11, 514ff
[7]    Keller, 1996, Hist Stud Phys Biol Sci 26, 313ff
[8]    Sumner & Prokop, 2013, dx.doi.org/10.6084/m9.figshare.741264
[9]    Gibney, 2014, Nature 513, 129ff
[10]    Roote & Prokop, 2013, G3/Bethesda 3, 353ff
[11]  Prokop, 2013, dx.doi.org/10.6084/m9.figshare.106631
[12]  Kelty, 2012, BioSocieties 7, 140ff
[13]  Fostier et al., 2015, G3/Bethesda 5, 689ff
[14]  Redfield, 2012, PLoS Biol 10, e1001356ff
[15]  Prokop, 2013, dx.doi.org/10.6084/m9.figshare.156395