Drosophila

Why funding fruit fly research is important for the biomedical sciences

Andreas Prokop science communication , , , , , ,
This blog post was originally published in the Journal Open Access Government. and provides a concise overview of the rationales for fruit fly research in the biomedical sciences.

Prologue: an impressive past and presence

For 30 years I have been studying the nervous system of the fruit fly Drosophila melanogaster, the tiny insect that hovers over our fruit bowls in summer (Prokop, 2016). You may wonder why anybody would invest professional time or public money in something that seems more of a private hobby than serious research. But I am not alone: fruit flies have been intensively studied for over 100 years, and worldwide over 10.000 scientists are currently estimated to engage in fly research; and their work has great impact: nine (arguably ten) researchers have received a Nobel Prize in ‘Physiology or Medicine’ for their work in Drosophila – the last one as recently as 2017 (Fig. 1). As will be explained here, the biomedical sciences would be very far behind their current status quo without research in fly or other simple organisms, such as the nematode worm C. elegans or baker’s yeast.

Fig. 1 Researchers awarded with the Nobel Prize for work on Drosophila in 1933, 1946, 1995, 2004 (only marginally for fly work), 2011 and 2017. For image sources click here.

Why the fly? A historical perspective

Fig. 2 Flies as an efficient starting point of a translational pipeline.

Kick-starting genetics

Mere serendipity set in motion the long-lasting interest in fruit flies: in 1910, studies on evolution by Thomas Hunt Morgan led to the almost accidental finding that genes lie on chromosomes. This started the era of Genetics – with Drosophila research leading the field unravelling how genes are organised, become mutated or interact with each other (Allchin, 1997; Brookes, 2001; Kohler, 1994).

Genetics as a tool

In the middle of the 20th century, researchers started to use Drosophila genetics to address the essential question of how genes work and determine biology. In the same way as mutations in humans cause inherited diseases that tell us something about the biological relevance of those genes, mutations can be used in Drosophila research as a tool to dissect and understand biological processes. The fly was ideal because genetic manipulation techniques were well established, its generation cycle of only 10 days allowed fast progress, and the ease of keeping big numbers of flies, facilitated systematic ‘mutational screens’ to search for new genes that contribute to biological processes (Fig. 2). Drosophila became “a boundary object par excellence, residing in the interstices of two major disciplines, genetics and embryology” (Keller, 1996). Together with the advent of molecular biology (to decipher and manipulate genes) and advances in biochemistry (to study the protein products of genes), fly research turned into a gold mine for discovery. For example, genes that mediate embryonic development, nervous system function or even the ability to learn were discovered and studied, pioneering fundamental understanding of those processes (Mohr, 2018).

A translational path to humans

Through parallel work in vertebrate animals, in particular the mouse, it became increasingly clear that fundamental concepts discovered in the fly seemed to apply to all animals: genes studied in mammals turned out to be very similar in structure and function to their fly equivalents; in some cases it was even shown that genes from fly and mouse were interchangeable. The scale of this ‘evolutionary conservation’ became clear when the human and fly genomes were sequenced and compared. As Ethan Bier and colleagues commented at the time: “… about 75% of known human disease genes have a recognisable match in the genome of fruit flies” (Reiter et al., 2001). The fundamental truth behind this statement was unequivocally documented by a systematic study using 414 yeast strains with lethal mutations, of which almost half could be ‘cured’ by introducing the equivalent human gene (Kachroo et al., 2015; Leslie, 2015). Therefore, fundamental processes of biology and the genes involved are ancient; organisms that shared their last common ancestor a billion years ago have maintained many of these fundamental functions to astonishing degrees. This concept of ‘deep homology’ explains the above mentioned Nobel laureates: through their work they have laid foundations for fundamental understanding of biological processes which can explain to us what goes wrong in human disease and pave the translational path into the quest for cures.

The importance of Drosophila research is undiminished

The last decades have brought new strategies for research in mice and other vertebrate animals that have now turned also these organisms into true boundary objects. The fairly recent advent of CRISPR technology is widely seen as the magic silver bullet that has finally closed the experimental gap to research in smaller invertebrate models. However, I would argue that this is a dangerous misconception likely leading to increased research costs, unnecessary use of animals and a slow-down in scientific advance.

Hugo Bellen, a renowned and highly successful researcher, was cited to have said: “You get 10 times more biology for a dollar invested in flies than you get in mice” (Levitan, 2015). To illustrate this point, keeping 400 fly stocks requires one stand-alone incubator and £100 a month to pay for food vials and 4-6hrs of work (Fig. 3); maintaining the same number of mouse strains readily accessible would take at least £12.000 a month and a vast housing facility. Furthermore, CRISPR technology certainly has enormously accelerated mouse research, but it is also well established in Drosophila and has enhanced the possibilities of fly research to the same degree. Many more arguments can be listed (Prokop, 2015), but I would like to focus here on one last, enormously important aspect: the fact that biology is complex.

Fig 3. Maintaining and handling flies in the laboratory. A) A ~10 cm high vial containing flies. B) 400 different fly stocks kept in one incubator. Genetic crosses are performed under a stereo microscope (C) on CO2-dispensing porous pads (D) to carefully inspect the immobilised flies (E).

Thus, to understand inherited diseases, it is often not sufficient to gain important knowledge of the affected genes and their products; it requires an understanding of the usually complex functional networks in which they operate (Prokop, 2016). An important strategy to unravel complex genetic networks is the simultaneous manipulation of two or more genes in the same individual – a task that is routinely performed in a fly laboratory, but enormously laborious and time-consuming in mice. Furthermore, experiments, even if based on well-informed rationale, often fail. In fly, such failure is unfortunate but can be easily absorbed, since time and money invested are usually low, with alternative experiments being set up in a matter of days or weeks rather than months or beyond. Hence, work in fly gives access to flexible experimentation, where try-and-error is a feasible strategy to overcome the challenging enigmas posed by biological complexity.

Conclusions

Understanding biology is the lifeblood for translational research into human disease and, as I have argued here, Drosophila research is a powerful generator of such understanding. Certainly, fly is NOT a mini-human. For example, it cannot be used to study arthritis or fibrosis, but it can be used to understand fundamental concepts of extracellular matrix regulation underlying those problems. In the context of Alzheimer’s disease, flies are unsuited to study personality loss, but can be used to address the still unresolved important question of how this condition triggers nerve cells to die. In any case, the use of any experimental models should always be carefully justified. Consequently, funding panels should, in my opinion, more often question the uses of higher animals where fundamental concepts could be pioneered more efficiently in simpler models – thus spending research money responsibly and speeding up the discovery process.

 

The author, Andreas Prokop, is Professor for Neurobiology at The University of Manchester. As academic head of the ‘Manchester Fly Facility’, and together with his colleague Sanjai Patel, he drives the ‘droso4public’ science communication initiative advocating the wider awareness of fly research (droso4public.wordpress.com). Part of this initiative is the ‘droso4schools’ project (droso4schools.wordpress.com) aiming to establish Drosophila also as a powerful teaching tool in school biology lessons.

Cited literature

A novel engaging approach to teaching life cycle and evolution in KS2 classrooms (primary schools)

Andreas Prokop science communication , , , , , , , , , , ,
This blog post was written for school teachers and will hopefully soon be published on a suitable blog site that reaches teacher audiences. It has been put up here to serve as reference for “droso4schools” activities. It describes our first primary school resources and first event on which we tried them out in their final form, accompanied by evaluation.

Prologue: a need to bring nature into classrooms

Nature is fascinating. One can easily be gripped by the many natural history documentaries engaging us with fascinating insights into the plant and animal world. My kids can still be tempted to watch them together with us, but would unfortunately not pick them if given a free choice. But isn’t it that the more we know about nature around us, the more we care for it? Can schools be a place where to address this challenge? The two lesson resources I am describing here can help teachers to bring natural history spirit and practical science into primary school classrooms whilst teaching the curriculum-relevant topics of life cycle and evolution.

Fig. 1 Some of the insect images used in this resource. For details see our website.

Why I developed these teaching resources

The topics of inheritance, evolution, life cycle and ageing are key specifications of the English KS2 curriculum (Box 1). I learned about all these topics during my traditional university biology education 30 years ago. Although I now work on very different areas of biology, those memories still live on vividly, which is why I am convinced of the powerful influence of early experiences. Such prolonged impact seems to work similarly for pupils at younger age (Archer et al., 2012; Croll, 2008; Maltese and Tai, 2011) emphasising that we must care about excellent school teaching of science and natural history.

Box 1 Statutory guidance for the national science curriculum of key stages 1 and 2 (Department for Education, 2015)

Pupils should be taught to

  1. describe the differences in the life cycles of a mammal, an amphibian, an insect and a bird
  2. describe the life process of reproduction in some plants and animals
  3. describe how living things are classified into broad groups according to common observable characteristics and based on similarities and differences, including micro-organisms, plants and animals
  4. give reasons for classifying plants and animals based on specific characteristics
  5. describe the changes as humans develop to old age
  6. recognise that living things have changed over time and that fossils provide information about living things that inhabited the Earth millions of years ago
  7. recognise that living things produce offspring of the same kind, but normally offspring vary and are not identical to their parents
  8. identify how animals and plants are adapted to suit their environment in different ways and that adaptation may lead to evolution

A second incentive for generating these resources comes from my scientific research based on using Drosophila melanogaster, the tiny fruit flies that hover over our fruit bowls in summer (Prokop, 2016). I use these flies for good reason, because more than a century of intense research have made them the animal organism with the best understood biology on this planet (Prokop, 2018b; Why fly?). This unique understanding offers fantastic opportunities not only for research, but also to enrich biology teaching in schools: with (1) conceptually well understood contents (including all topic areas mentioned in Box 1), (2) many relevant examples and anecdotes, as well as (3) numerous micro-experiments that are easy to perform in classrooms (Manchester Fly Facility, 2015). Astonishingly, many aspects of fly and human biology are so similar that Drosophila research has helped us understand many aspects of our own bodies and even human diseases. This shared biology can be capitalised on in classrooms: for example by first using fly to explain fundamental concepts to then demonstrate how this applies to humans; or to illustrate the concept of common evolutionary roots (see below).

Since we want more people to become aware of the enormous potential of fly research, we launched the “droso4schools” project which actively promotes the introduction of fruit flies as teaching tools in schools. The goal is to improve curriculum-relevant contents whilst creating memorable encounters with flies. Our evaluations clearly show that pupils receive Drosophila and fly-based micro-experiments with great enthusiasm (see our impact document; Fig.11 below).

It is for all these reasons that I developed the two lesson resources described in the following.

Fundamental strategies for our biology classes

On the droso4schools project, university students work as teaching assistants in partner schools for several months (Harbottle et al., 2016; see our film). Through this close involvement we are able to generate sample lessons where we merge our own expertise on biology topics with the professional expertise of teachers, thus incorporating appropriate styles of teaching including differentiation, as well as contents that address the curriculum and assessments.

Fig. 2 Logo of the droso4schools website

Our sample lessons form a conceptual journey through curriculum-relevant topics, told in a highly interactive way that engages the pupils. The lessons are spiced up with little activities and micro-experiments that are easy to set up and perform also by teachers. These sample lessons are made freely available for download from our figshare site. They include PowerPoint files accompanied by support materials, such as teacher notes, lesson plans, risk assessments, activity and homework sheets. Importantly, these resources are not static but regularly updated and improved, based on new ideas that arose during our school visits or other forms of feedback we receive. Notably, all contents are also provided as dedicated pages on our “droso4schools” website, which can be used for teacher preparation as well as revision or homework tasks of pupils.

So far, most of our experiences are derived from collaborations with secondary schools (Prokop, 2018c), whereas primary schools are new territory for our project. But our first school visits and evaluations were promising, and we felt it to be timely to share our resources – also hoping that members of the teaching community may send us their feedback, advice and suggestions so that we can further improve our lessons.

A KS2 lesson on life cycle

Box 2 Flow of the life cycle lesson

(0)   two weeks ahead of the lesson, get vials with fruit fly eggs (to obtain them, please contact us) so that pupils can observe them and protocol their findings on a daily basis;

Fig. 3 An animated image showing the life cycle of the fruit fly Drosophila melanogaster as it can be used and viewed in classrooms. For details see our website.

(1)   show the three subclasses of amphibians (letting the pupils guess what they are and providing some background information), and discuss their life cycles;

(2)   look at incomplete metamorphosis of dragon- and damselflies (Odonata) and compare their life cycles to those of amphibians with tadpoles;

(3)   see a National Geographic film about mayflies (who only live one day as adults);

(4)   discuss grasshoppers/crickets (to demonstrate an example of less severe metamorphosis);

(5)   use butterfly/moth life cycles to introduce to complete metamorphosis and pupal stages;

(6)   engage in an activity where the pupils identify different insect orders and try to guess whether they have a pupal stage (accompanied by an activity sheet);

(7)   discuss the pupils’ own protocols of the fly life cycle (see Fig.10 below); show an image of a Drosophila maggot versus adult fly and ask pupils to compare them;

(8)   explain how metamorphosis works using examples from Drosophila (supported by films and graphics): newly developing legs and wings as well as transforming muscles;

(9)   show a film with mosquito larvae and let pupils guess what they are, then discuss their life cycle;

(10) lead over to mosquito-borne parasites and discuss the life cycle of the malaria parasite Plasmodium and how it causes malaria (mention the importance of prophylaxis if travelling into malaria-infested regions);

(11) show images of worm parasites, then discuss the life cycle of the dog tapeworms (vividly illustrating why pupils should wash their hands!);

(12) a potential further activity or homework task introduces pupils to the identification of insect orders using determination keys (we use the UC Berkely BioKeys website).

The flow of our life cycle lesson is summarised in Box 2, and contents are explained in the wider conceptual context on our accompanying webpage (Prokop, 2018a; see Appendix). Here I briefly discuss some innovative features of this lesson.

First, when analysing existing online life cycle resources, I mostly encountered materials with lovely drawings but very few would show the real animals. I therefore took a different approach in that my lessons make prominent use of animal photos. In the life cycle lesson these cover the four known groups of amphibians as well as most orders of insects. Many of these animals are set into context, and engaging background information is provided. We even explain how teachers can extend into an activity where children learn simple and exciting ways to use a determination key to identify animals they might find outside in their daily lives. In sum, these contents and activities clearly address items 1-4 in Box 1, whilst bringing natural history into the classroom.

Fig.4 Damselflies (left) and dragonflies (right) belong to the insect order of Odonata and are easily distinguished by their eye sizes (insets), wing shapes (see details) and wing postures in resting position (see main images). Image information: Ischnura heterosticta (inset – same species); Sympetrum flaveolum (inset  – species unknown).

Second, the use of Drosophila brings new opportunities. For example, observing the full life cycle of flies in only 10 days in the classroom is a memorable way to experience complete metamorphosis. It can even be used for experiments. For example, when comparing fly vials placed closer to a radiator with those further away, the influence of temperature on biological processes of cold-blooded animals (including insects and amphibians) can be demonstrated. Or mutant flies of different body or eye colour can be used, thus challenging the children to spot small differences (if you need suitable flies, please contact us).

Fig. 5 Comparing maggots and flies. Image sources: Sekelsky lab; Discover Life (by Malcolm Storey)

Furthermore, fly maggots are drastically different from adult flies (Fig. 5) and do not even have stumpy legs like caterpillars. This poses the obvious question of what actually happens within the pupal case. In flies this question has been answered in unprecedented detail. Building on this knowledge and supported by graphic illustrations and little films, we show how muscles of crawling maggots are rebuilt to enable walking and flying, and how legs and wings are formed anew. Notably, pupils also learn that tongue development in frogs occurs during metamorphosis in ways comparable to leg/wing development in flies.

We were surprised to find that only a few kids could identify mosquito larvae (a common and easy to spot guest in puddles and buckets in our gardens!), but many knew malaria as a mosquito-borne disease. Accordingly, pupils appreciated the life cycle of the malaria parasite Plasmodium, which starts in humans and then continues in mosquitoes. For this, I provide a step-wise animation which makes it easy to explain the enormously complex Plasmodium life cycle. The lesson leads over to parasitic worms and the example of the tapeworm life cycle is briefly discussed (Fig. 6), which tends to have a gripping “horrible history”-like effect on the pupils. Importantly, the life cycles of both parasites represent relevant examples relating to disease: Plasmodium illustrates the importance of malaria prophylaxis (for kids travelling into malaria-infested areas) and the tapeworm clearly illustrates why we should wash our hands after being outside.

Fig. 6. The dog tapeworm: an unusual but didactically valuable example of life cycle, relevant for understanding needs of daily hygiene. For details see our website.

A KS2 lesson on evolution

Box 3 Flow of the evolution lesson

(1)   discuss some aspects of fruit flies including gender differences, and the Antennapedia mutation where flies have 8 legs;

(2)   show photos of 8-leged spiders and other related arachnids including mites (dust allergy!) and ticks (lime disease, tick-borne encephalitis!); let pupils guess what they are;

(3)   show their scientific names to lead over to discussing the concept of “binominal nomenclature” (two-name naming system, such as in “Tyrannosaurus rex”);

(4)   lead over to Darwin and ideas of speciation and evolution;

(5)   discuss mutation as the key driver of change, and use albinism and the peppered moth as examples to explain natural selection;

(6)   identify Drosophila marker mutations under the microscope (Fig.7) or as a digital exercise (for advice on affordable microscopes or the digital version, please contact us);

(7)   together with the pupils, construct an invented evolutionary tree based on Drosophila mutations (Fig.8);

(8)   lead over to the human evolutionary tree to introduce the “common ancestor” concept;

(9)   point out that the common ancestor of humans and flies lived 500 million years ago, and explain commonalities between fly and human body functions to illustrate that fundamental principles of biology are ancient and have been maintained (concept of ‘deep homology’);

(10) show examples of evolutionary conservation between flies and mammals (Fig.9) including movies of fighting (aggression!) and “free-climbing” (motivation!) flies;

(11) pose the question of whether we can study ageing in a fly that only lives for 7-8 weeks; test this with an experiment racing young against old flies; data are plotted and then discussed in front of the class to show how data can be generated and interpreted.

The flow of our evolution lesson is summarised in Box 3, and most contents are explained on our accompanying webpage (Prokop, 2018a). One innovative aspect is the introduction of “binominal nomenclature“, i.e. the two-name naming system of animals, plants and microbes (such as in “Tyrannosaurus rex”). Its underlying concepts are explained with engaging and surprising examples (e.g. the “pomato“). The lesson uses binominal nomenclature as a gateway to an understanding of animal classification (covering items 4 and 5 in Box 1).

Fig. 7. A simple activity identifying fly mutations under the microscope (also available as a digital exercise)

Using fruit flies offers unique and unusual opportunities for evolution lessons. For example, we use so-called “marker mutations” affecting the flies’ body colours, eye shapes & colours, wing shapes, or bristle shapes & numbers. These changes to the flies’ anatomy are easily spotted by young kids under the microscope (Fig.7; for info about cheap microscopes, please contact us, or if you prefer to perform the experiment with digital images). We then capitalise on these mutations by constructing step-by-step an invented evolutionary tree (Fig.8). This is intended to bring home to the pupils how random mutations can provide opportunities and be selected for, leading to new species over time.

Fig. 8. Using “marker mutations” of Drosophila to construct an invented evolutionary tree

The fact that fly research has helped us understand human disease (Fig. 9), is a fantastic starting point to think about the concept of “deep homology”. The idea behind this concept is that flies and humans shared a common ancestor organism about 500 million years ago. This ancestor had many aspects of biology readily established, which were so fundamental that they have been maintained in the many life forms that evolved from it.

Fig. 9 Examples of related fly and human genes which cause comparable defects when functionally affected: loss of Pax6 causes blindness/eye loss, and gain of hedgehog (Shh) causes extra digits/wings. Note that functions are so well conserved that the Pax6 gene from mouse can cure the defect of flies and bring back its eyes. Images taken with permission from: Washington et al., 2009, PLoS Biol 7, e1000247ff.; www.primehealthchannel.com/polydactyly.html; Tabata, 2001, Nat Rev Genet 2, 620ff.   

We capitalise on the concept of deep homology by finishing up with a simple, yet highly memorable experiment. Pupils are asked whether they would win a race against their grandparents, to then discuss what happens to our bodies during ageing (item 5 in Box 1). Pupils then vote as to whether they think that a fly life of 7-8 weeks is long enough to show symptoms of ageing – i.e. whether we can study ageing in flies. We take this to the test in that pupils perform a race experiment: flies have the tendency to walk upwards in their vials; so pupils bang them down and measure the time at which the first young and the first old fly arrive at the top (referred to as the “climbing assay”). Data are collected across the class and plotted live in front of their eyes. Pupils quickly see that young flies are faster, thus discovering the answer to the question of this experiment. We discuss the obtained “data clouds” as being typical of biological experiments; pupils are then usually able to suggest that means/averages are a way to describe these data and turn them into bar graphs.

Epilogue: How well do these lessons and their objectives work in practice?

For several years, we have taught various parts of these lessons in higher classes of primary schools and lower classes of secondary schools. On 17 October 2018 we were invited by St. John’s RC Primary School in Manchester to teach both lessons in parallel in two consecutive sessions: first to two year 5 classes (aged 9-10), then to two year 6 classes (aged 10-11). A team of four took on the task (Fig. 10), for which we brought 25 low-cost stereomicroscopes (for looking at mutants), flies and empty vials (for the climbing assay), as well as the various activity and evaluation sheets. Ahead of the event, teachers had watched our 5 minute educational movie together with the pupils, to introduce them to Drosophila as a laboratory model, and had observed vials with fly eggs for two weeks to protocol the fly life cycle (Fig. 10).

Fig. 10 Left: The team visiting St. John’s RC Primary: Andreas Prokop, Sanjai Patel, Megan Chastney, Ben Chapman. Right: Class display illustrating engagement with the fly vials provided 2 weeks ahead of the event.

The flow of lessons during this first comprehensive trial worked in a highly interactive manner, with pupils staying alert. The evaluation forms were filled in with the help of teachers on the following day and turned out to be very encouraging (Fig. 11; Box 4). Most pupils seem to have enjoyed the event and felt they had learned new facts about animals, life cycle and evolution – suggesting that our ideas are in principle working and can reach year 5 and year 6 pupils. This said, the level and amount of selected contents was intended to be demanding, and proper implementation for routine use in schools would require suitable differentiation strategies to reach children of varying abilities. Furthermore, the evaluation only reflects what the pupils felt; it would require more detailed studies to assess whether this correlates with true learning, and follow-ups would be needed to investigate long-term retention.

Fig. 11 Evaluation of the event on 17 Oct 2018  teaching the Life Cycle and Evolution lessons to Y5 and Y6 classes at St. John’s RC Primary School in Manchester. The complete spread sheet can be downloaded here.

To facilitate retention, we designed further strategies and resources. Thus, children were given three activity sheets (LINK1, LINK2) designed to be filled in with the teachers in school or as a homework task (potentially engaging further family members!): (1) an aide-mémoire which was filled in during the lesson and displays different insect orders and whether they have a pupal stage; (2) a sheet explaining the UC Berkeley BioKeys activity; (3) a crossword puzzle as an incentive to look at the accompanying website (Prokop, 2018a) and our 2nd educational movie. However, to achieve that these resources serve their intended purpose of consolidating knowledge, we are aware that schools are busy and that we need to develop clever strategies of incentivisation and closely collaborate with teachers to make sure that these resources are being capitalised on.

Finally, regarding the aims of our droso4school initiative, most pupils found that flies and the fly experiments were great fun and exciting (Fig. 11, Box 4), suggesting that flies seem to work as suitable teaching tools also in primary schools. For the majority of pupils it was new that fruit flies were used in research, and disagreeing students might have known from hearing about our previous events at the same school. But from their comments we take the careful hope that many of these kids will remember Drosophila in the future, and that the experiences of this extracurricular day will make them respond with greater attention and curiosity when hearing about fruit fly research from the media or elsewhere.

To extend this outcome beyond Manchester, we made all our teaching resources public and are working hard to spread their active use within teacher and researcher communities; comments that we received on other lesson resources from across the world show that this is in principle possible (see our impact document). However, the impact could be even greater if examination and education boards incorporated Drosophila into the national curriculum – and this is what we are aiming to achieve (see also Prokop, 2018c)!

Box 4. Some pupils’ comments

  • It was one of my best days ever (Y5)
  • The lesson was amazing, most of it I didn’t even know about (Y6)
  • This lesson was very cool and interesting. I might even go to Manchester University (Y6)
  • I could understand everything. I loved the experiments the best (Y6)
  • The lesson was very fun and I hope we have more amazing experiences like that again (Y6)
  • The lesson was exciting because of the fruit flies (Y5)
  • I really enjoyed looking at fruit flies through a microscope (Y5)
  • I think we should do more work on fruit flies, it’s very interesting (Y5)
  • Using fruit flies made the lesson so much more fun and interesting (Y5)
  • Using the fruit flies made the lessons exciting. It was amazing. It made me have a better understanding about them and the stages they go through (Y6)
  • I understand much better how evolution works (Y5)
  • I didn’t know a lot about evolution but now I do (Y6)
  • I know much more about evolution and our distant relatives (Y5)
  • At first I didn’t know about how evolution works but now I do (Y6)
  • Evolution can help animals adapt to new habitats or to help them to have new advantages and have new abilities (Y6)
  • I loved learning about different creatures and different insects (Y5)
  • Lots of interesting facts about many different animals I didn’t even know existed (Y5)
About the author: Andreas Prokop is Professor of Neurobiology at The University of Manchester. As academic head of the ‘Manchester Fly Facility’ and together with the facility’s manager Sanjai Patel, he drives the “Manchester Fly Facility” and ‘droso4schools‘ initiatives mentioned in this blog post.

References

Archer, L., DeWitt, J., Osborne, J., Dillon, J., Willis, B., Wong, B. (2012). Science Aspirations, Capital, and Family Habitus:How Families Shape Children’s Engagement and Identification With Science. American Educational Research Journal 49, 881-908 — [LINK]

Croll, P. (2008). Occupational choice, socio‐economic status and educational attainment: a study of the occupational choices and destinations of young people in the British Household Panel Survey. Research Papers in Education 23, 243-268 — [LINK]

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]

Maltese, A. V., Tai, R. H. (2011). Pipeline persistence: Examining the association of educational experiences with earned degrees in STEM among U.S. students. Science Education 95, 877-907 — [LINK]

Manchester Fly Facility (2015). droso4schools: Online resources for school lessons using the fuit fly Drosophila — [LINK]

Prokop, A. (2016). Fruit flies in biological research. Biological Sciences Review 28, 10-14 — [LINK]

Prokop, A. (2018a). LESSON 6 – Life cycles. Blog post in “droso4schools” — [LINK]

Prokop, A. (2018b). Why funding fruit fly research is important for the biomedical sciences. Open Access Govern 20, 198-201 — [LINK]

Prokop, A. (2018c). How to communicate basic research in schools – a case study using Drosophila. Blog post in “PLOS | BLOGS” — [LINK]

Appendix 1

Information on the accompanying website covers all of the contents of the life cycle lesson and most of the evolution lesson. Some information goes beyond these contents to provide a wider context; it comprises the following topics:

  • What role do sexual versus asexual modes of reproduction play in plants and animals. The horticultural practice of grafting is also explained in this context.
  • How do different plant or animal species distribute gender? For example, hermaphroditic snails or earthworms in our garden are male and female at the same time, or clown fish can change gender from male to female.
  • How does the reproduction of plants and animals compare to that of bacteria or baker’s yeast?
  • How do life cycles link to evolution? In this context, the example of the peppered moth is explained and the relevant topic of bacterial resistance to antibiotics is explained.
  • What is development and how does it relate to the topic of reproduction and life cycle?
  • The information about these five insect orders also covers typical features of their aquatic larvae typically occurring in our ponds or rivers (Fig. 5). This might be helpful for an outside activity.

Fig. A1 Embryonic and juvenile development. For further details see our website.

 

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

Andreas Prokop Uncategorized , , , , , ,
The first version of this blog was published on the pedagoo.org site.

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 articles (see resource box below) and the 1st 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 . Furthermore see our repository with downloadable resources for extracurricular school visits (LINK).

Our resources for teaching Drosophila
(for researchers an teachers alike)

  • 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]
  • Patel, S., DeMaine, S., Heafield, J., Bianchi, L., Prokop, A. (2017). The droso4schools project: long-term scientist-teacher collaborations to promote science communication and education in schools. Sem Cell Dev Biol, published online — [PDF]
  • Dedicated droso4schools website with supporting information for teachers, pupils and the wider public [LINK]
  • A repository with sample lessons for biology lessons [LINK]
  • A repository with outreach resources for extracurricular school visits (and science fairs) [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?

Drosophilist
“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.

  • DSC_6939
    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.
flies-compo
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

FlyLifeCycle-3
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

A scratch computer game based on the Drosophila life cycle.
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).

Fig2-organs
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.
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 more information.
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

MotorneuronCircuit-2
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.
Climbing-2
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
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.

DSC_6893
Students performing the genetic marker exercise.

(7) Fundamental principles of the nervous system

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

(8) Metabolic pathways: investigating the biology & chemistry of pigmentation

This lesson and its adjunct support materials can be downloaded from our figshare repository. The online resource can be found here. The lesson is a synoptic resource suitable for Biology A Level (KS5), ideal for end-of-term revision lessons. It starts with the phenomenon of human skin colour, the advantages and disadvantages of dark and light skin, which may explain why they are distributed differently across the globe. By identifying melanin as the pigment reponsible, the lesson raises the question how such complex organic molecules can be produced, leading over to enzymes, and enzymatic/metabolic pathways. Fundamental principles of these pathways are explained, and then Drosophila eye pigmentation is introduced as an example to illustrate how genetics and biochemistry are used in combination to unravel metabolic pathways. For this, pupils are given chromatography results of normal and mutant flies which display changes in their eye colours and work out the enzymes affected by the respective mutations. This understanding is then related back to the initial question of human skin pigmentation: (1) first comparing and contrasting metabolic pathways of fly eye and human skin pigment, then (2) understanding how skin tone can be changed as the outcome of genetic alterations of the metabolic pathway and, eventually, (3) how evolutionary selection processes can explain the different distribution of skin colour across the globe. This resource is accompanied by a worksheet for the chromatography analysis and a homework task recapitulating some areas of the lesson and beyond, but also helping students revise and consolidate knowledge from several areas.

Simple illustration of a metabolic pathway

(9) Vision: Understanding light perception

This lesson is not yet available online, but please request the presentation and adunct materials from Andreas.Prokop@manchester.ac.uk . The online resource can be found here. This lesson is a synoptic resource suitable for Biology A Level (KS5), ideal for end-of-term revision lessons. The lesson starts by recalling fundamental knowledge about our senses, with emphasis on visual information obtained from our environment. It then focuses on light and light perception, starting with the physical nature of visible light as a small fraction of the wide spectrum of electromagnetic waves, which are introduced via a brief interactive PowerPoint animation. The question is posed as to why we see only this narrow fraction of the spectrum, providing our evolutionary origins in the oceans as a likely explanation because visible light is little absorbed by water and reaches fairly deep down. The lesson then explains the principle of seeing an object by reflection (also introducing to the subtractive colour model), and introduces to eye anatomy by comparing a lens eye to a camera. In a comparative approach, lens eyes are compared to compound eyes of the fruit fly Drosophila (as typically found in arthropods, such as insects, crustaceans, arachnoids). For both eye types, the idea of perception in the eye and conduction to the brain for information processing is explained. The next topic is phototransduction (i.e. the transformation of light into nerve impulses). It starts with the stereo-isomerisation of retinal embedded in opsins and the subsequent triggering of a signalling pathway which eventually elicits the nerve impulse sent to the brain. This process is explored using an animation which the pupils interpret step-by-step. A micro experiment uses Drosophila to explore the idea of positive phototaxis (movement towards light) as a measure to explore what colours of visible light an animal can sense. Then sevenless mutantf flies and Ishara plate tests are used to introduce to the idea of colour blindness. The underlying concepts of cone cells with three different colour opsins are introduced together with the additive colour model and the idea of mutations that affect opsin genes. Finally, red-green blindness is used as an example of X-chromosomal inheritance, also reminding of the uses of Punnett squares.

Comparing our eye to a camera

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