The organisation and function of the nervous system and its synapses

Andreas Prokop Uncategorized , , , ,

Nervous system anatomy and organisation

The nervous system processes sensory information and coordinates behaviours including movement, decision-making, learning and memory, but also subconscious performances such as sleep, breathing, sweating and gut peristalsis. It can be crudely divided into (Fig.1):

  • the central nervous system (CNS) composed of the brain and spinal cord;
  • the peripheral nervous system (PNS) which is mainly composed of the nerves that contain the nerve fibres of lower motorneurons, sensory neurons and autonomic neurons; the PNS also includes the dorsal root ganglia containing the cell bodies of sensory neurons and autonomic ganglia harbouring the cell bodies of the postganglionic autonomic neurons.

Fig1-InnovAIT.ai

Fig.1 Nervous system organisation. A) Frontal view of a body, colour coded to indicate head, cervical, thoracic, lumbar and sacral regions; the positions of upper/lower motorneurons and sensory neurons with their extremely long nerve fibres are indicated. B) side and back view of the CNS; different brain and body regions are colour-coded (see Box 1) and the locations of peripheral and autonomic nerves including their ganglia are shown. C) Wiring diagram of a reflex circuit and how it connects to the brain (see below).

The Central Nervous System
The CNS is composed of the brain and the spinal cord (Fig.1B). The Brain is the control centre, subdivided into functionally distinct regions dedicated to the orchestration of often well-defined aspects of our behaviour (Box 2). Accordingly, lesions in different areas of the brain will cause characteristic behavioural deficits that explain the symptoms of those degenerative neural diseases (DNDs) affecting these areas (Box 1).

Box 1. Key functions and associated degenerative neural disorders of different brain regions, spinal cord and sensory system (compare Fig.1 for illustrations).

  • The cerebral cortex is the outermost layer of the brain with its characteristic folds found only in humans and apes. It is subdivided into different regions: for example, the primary somatosensory cortex receives and processes sensory information from the skin and musculoskeletal organs, the visual cortex from the eyes. Two regions have strong links with DNDs:
    • The primary motor cortex contains the upper motor or pyramidal neurons with nerve fibres that reach up to a meter into the spinal cord to instruct voluntary muscle movements; DNDs affecting upper motor neurons include MND, HSP or MS and are associated with body paralysis.
    • The prefrontal cortex coordinates highly complex behaviours such as decision-making and personality expression; it explains personality loss in FTD patients.
  • The hippocampus mediates consciously aware (explicit) learning and memory formation; it is usually the first area affected in AD.
  • The substantia nigra is a mid-brain area rich in dopaminergic neurons and involved in the regulation of voluntary movement; it is primarily affected in PD patients, explaining the movement disorder.
  • The cerebellum is an accessory area to the hindbrain coordinating and fine-tuning motor functions; it is primarily affected in ataxias explaining lost motor control including balance and speech.
  • The spinal cord is the central nervous system of the body; it forms a long tubular structure extending from the brainstem down the vertebral column. It transmits information between the brain and the rest of the body and controls information flow in each body segment including the reflexes.
    • Lower motorneurons have their cell bodies in the spinal cord and form the long nerve fibres in our segmental nerves that innervate the somatic musculature.
    • Sensory neurons of the trunk have their cell bodies in dorsal root ganglia lateral to the spinal cord; they form long nerve fibres in our segmental nerves that convey information about stretch, heat, injury or body posture from the periphery to the spinal cord where these fibres often continue up to the mid brain (achieving lengths of up to 2 m in total).

The Spinal Cord is embedded within the vertebral column, organised into body segment-specific units, and composed of white matter and grey matter regions (Fig.1B, C).

  • The white matter forms the rind of the spinal cord. It contains myelinating oligodendrocyte glia (explained below) and the long nerve fibres transmitting information between the brain/head region and the trunk. It can be subdivided into ascending and descending tracts: for example, upper motor neuron fibres project through the descending pyramidal/corticospinal tract and many ascending sensory fibres through the dorsal column (Fig.1C). These long nerve fibres are interrupted in spinal cord injury explaining paralysis and loss of sensation below the point of injury. These nerve fibres are also affected in motor neuron diseases, multiple sclerosis or spastic paraplegia, explaining paralysis occurring in these diseases which can be accompanied by sensation loss.
  • The grey matter forms the butterfly-shaped central core in transverse sections of the spinal cord (Fig.1C). It contains the cell bodies and dendrites of neurons required for the local coordination of each body segment. For example, the ventral horn of the grey matter contains the cell bodies and dendrites of lower motor neurons (Fig.1C) which send nerve fibres through the peripheral nerves to innervate muscles of their respective body segments. These lower motor neurons are instructed by the upper motor neurons during voluntary movement. They are also innervated by muscle-specific sensory neurons to establish the local reflex circuits that trigger compensatory sub-conscious muscle contractions in response to posture change, important to keep our body in balance (Fig.1C). Deterioration of lower motor neurons causes paralysis, as observed in Charcot Marie Tooth disease, but also motor neuron diseases where both upper and lower motor neurons are usually affected.
  • EXPLAINER: The terms grey versus white matter are derived from anatomical sections treated with Nissl stain. This method primarily highlights subcellular components which are restricted to cell bodies and dendrites but are absent from axons. It therefore stains the central region of the spinal cord packed with cell bodies and their dendrites (hence grey matter) but very little the rind which contains mainly axons and far less abundant cell bodies of stained oligodendrocytes (hence white matter). Nissl stain is violet in nature but was first published by Franz Nissl in 1903 documented in grey scale drawings which might explain the term “grey” that is commonly used.

The Peripheral Nervous System
The Peripheral Nervous System (PNS) comprises the nerves and their associated ganglia in the head and trunk, which establish bidirectional connections between the CNS and the body (Fig.1B). Most nerves contain elements of both the voluntary somatic and involuntary autonomic nervous systems (SNS/ANS).

  • The ANS controls functions outside our conscious control. It is subdivided into the sympathetic and parasympathetic systems (light/dark grey in Fig.1B). The ANS is composed of preganglionic efferent neurons positioned in the grey matter of the CNS which project fibres to the peripheral para/sympathetic ganglia; in these ganglia, the fibre endings of preganglionic neurons form synapses onto postganglionic neurons which, in turn, send fibres to innervate the respective target organs. The most prominent ANS element is the vagus nerve which is mostly parasympathetic and controls functions such as heart and gastrointestinal movements or sweating (Fig.1B). The vagus nerve is also referred to as the 10th cranial nerve which also contains some voluntary elements, such as motor fibres controlling somatic muscles in the mouth region relevant for speech.
  • The SNS comprises outgoing motor fibres and ingoing sensory fibres. Examples of outgoing motor fibres are those of lower motor neurons in segmental nerves of the trunk or of oculomotor neurons innervating eye muscles via the 3rd cranial nerve. Ingoing sensory fibres carry information derived from sense organs in the head, joints, tendons and muscles, or from sensory nerve endings in the skin. Sensory neurons of the trunk have their cell bodies in the dorsal root ganglia (lined up on each side of the spinal cord; Fig.1B, C). From here they project a single nerve fibre reaching from the body’s periphery into the spinal cord, often sending a branch through the white matter up to the brain (Fig.1A,C). The cellular processes of a single sensory neuron can therefore extend almost 2 m from the tip of the toe to the brain (Fig.1A).

Sensory neurons are primarily affected in sensory neuropathies, as observed in hereditary sensory and autonomic neuropathies (HSAN) or as a complicating side effect in diabetes or upon cancer treatment (referred to as chemotherapy-induced peripheral neuropathy; CIPN).

What are synapses? Where are they located?

The nervous system coordinates the behaviour of animals and humans: it mediates perception of information (through the different senses), integration and processing of this information and, as a result, coordinates stimulation of muscles and glands. The nervous system is composed of different types of nerve cells which carry out these functions: sensory neurons (perception), interneurons (integration, processing) and motorneurons (stimulation of muscles and glands).These different nerve cell types are organised into complex networks. For this, the neurons carry cellular processes, the cable-like nerve fibres (axons), which propagate ‘electrical messages’ in the form of nerve impulses, passed on at synaptic contacts to other nerve cells, muscles or glands.
brain-neuronsNerve impulses (also called action potentials) are focal depolarisations travelling along axons (yellow cloud in the animation): usually, neurons are polarised, i.e. they display a voltage difference of up to ~70mV across their membranes (the outside of the neuron being zero, the inside negative); when a nerve impulse passes through (as a matter of milliseconds), dedicated pores open in the membrane that permit the flow of charged ions in a way that the voltage reduces to 0mV or even turns positive (depolarisation), and then immediately reverses back to negative potential (repolarisation) – thus curtailing the depolarisation and making it a very brief and local event (for more detailed explanations see here). The paths in which nerve impulses can propagate are defined by the way in which nerve fibres are laid out and connected within the nervous system and body, like the hard-wiring of an electrical circuit.
action-potential

How does synaptic transmission work?

Action potentials constitute information that can be passed on to other cells at synapses through a process referred to as ‘synaptic transmission’. At electrical synapses, the state of depolarisation (yellow arrow in left figure) can directly pass through open pores (gap junctions) that connect the pre- and postsynaptic cells; this transmission is fast but provides little means of regulation.
synapseIn contrast, transmission at chemical synapses occurs via translation of the action potential into chemical information and back into a nerve impulse (see right figure). The incoming action potential triggers the opening of calcium pores (voltage-gated calcium channels; green). The inflowing calcium (Ca2+) binds to certain proteins specialised to mediate the fusion of vesicles with the presynaptic membrane. These vesicles contain chemical neurotransmitter molecules (red dots) which are released into the synaptic cleft upon fusion and diffuse to bind to postsynaptic receptors (red). Upon neurotransmitter binding, these receptors open a pore for the flow of charged ions, thus triggering a new action potential in the postsynaptic cell (true only for excitatory synapses; see next section). Transmission at chemical synapses is complicated and far slower than at electrical synapses. But chemical synapses have many means to manipulate their function by strengthening, toning down or even blocking the transmission process. By changing transmission properties of synapses in this way, the information flow in neuronal circuits can be modified, which constitutes a key mechanism that can explaining the phenomena of learning and memory formation. For this reason it makes sense that most synapses in our bodies are of chemical nature.

How does an inhibitory synapse work?

syn-integrationThe image shows a postsynaptic terminal (post) innervated by two presynaptic terminals (pre), the top one being of excitatory (Ex), the lower one of inhibitory nature (In). The two terminal types use different transmitters and receptors (light grey, excitatory; dark grey, inhibitory). The colour code of the terminals represents their polarisation state relative to the extracellular environment (white; defined as zero), as indicated in the scale above. Three different scenarios are shown:

  1. Transmitter release from the excitatory (Ex) presynaptic terminal induces influx of positively charged ions (plus symbol) into the postsynaptic terminal causing a voltage shift from the resting state (here about -50mV) to less negative values (depolarisation). If a certain threshold voltage close to 0mV is reached, a postsynaptic nerve impulse is triggered (yellow arrow).
  2. Transmitter release from the inhibitory terminal (In) induces influx of negatively charged ions (minus symbol) driving the voltage from the resting state to more negative values (hyperpolarisation; dark blue), thus further away from the threshold voltage. Consequently, no nerve impulse is triggered.
  3. If both terminals release transmitter at the same time, the hyperpolarisation counterbalances the depolarisation. Therefore, the threshold close to 0mV is not reached and no postsynaptic nerve impulse is triggered.

How excitatory and inhibitory synapses are used in neuronal circuits

reflex-circuit-animatedThe neuronal circuits that mediate voluntary movements and local reflexes require both excitatory and inhibitory synapses, making them suitable examples to explain how these synapse types are used.  The animation shows two antagonising muscles of the arm, the flexor (bending the arm) and the extensor (stretching the arm). Two scenarios are shown:

  1. REFLEX: If an external force stretches the arm involuntarily, spindle organs sense the unexpected muscle stretch. This information is transmitted to the spinal cord via a sensory neuron (red). The sensory neuron forms an excitatory synapse onto a lower motor neuron (light blue; l-motor). This motor neuron innervates and triggers contraction of the same flexor muscle which harbours the stretched spindle organ. In this way, the sensory and motor neurons form a local reflex circuit where any involuntary stretch of the arm subconsciously triggers compensatory muscle contraction that keeps the arm in position.
  2. VOLUNTARY MOVEMENT: Voluntary movements are induced by excitatory upper motorneurons in the primary motor cortex of the brain (dark blue; u-motor). These neurons send long nerve fibres into the spinal cord where they form excitatory synapses onto lower motorneurons. In this example, the upper motor neuron innervates the lower motor neuron which can instruct the extensor muscle to contract, thus inducing voluntary stretch of the arm. In this case, the reflex circuit of the flexor muscle MUST NOT BE ACTIVATED. To achieve this, the upper motor neuron co-innervates interneurons which form inhibitory synapses on the flexor motor neuron (beige; inter). In this constellation, the sensory neuron which responds to flexor muscle stretch, tries to activate the flexor motor neuron, but this is blocked through the simultaneous inhibitory innervation through the interneuron (red circle), thus preventing reflex circuit activation.

Drosophila community resources for public engagement and advocacy

Andreas Prokop Uncategorized

THE RATIONALE

logoEDSThose working with Drosophila know about the fruit fly’s potential to drive discovery processes in the areas of biomedical sciences, evolution, behavioural science, biophysics or population genetics. But are we aware of how little this tends to be understood by those working with ‘higher’ model organisms, let alone the large group of non-biologists including medics, politicians, journalists, neighbours or family members?

Have you got an effective, enthusiastic and easy-to-follow elevator pitch ready that explains your research (and the enabling role of Drosophila within) to the kind of lay audiences mentioned above? Did you consider that these pitches might fly well even at grant panels?!

There are important reasons for engaging with the wide range of non-specialist/drosophilist/biologist audiences and build bridges toward a better understanding through science communication, science education and advocacy. However, to do this efficiently, we must have ..

  • .. a realistic view of the strengths of the fly as a model, its feasible applications but also limitations;
  • .. awareness of the conceptual knowledge gaps that hold specific target audiences back from seeing and appreciating the opportunities and specific advantages provided by fly research;
  • .. an understanding of the strategies and modalities that can be used to raise curiosity and catch attention of particular target audiences;
  • .. an awareness of resources readily available to you that can facilitate and speed up any audience engagements – ensuring hat the wheel is not re-invented over and over again.

In the following, we list links to resources providing means, ideas and strategies for successful fly training, teaching and advocay. Please, don’t hesitate to tell us about additional links that we may have missed!

AVAILABLE RESOURCES

Drosophila as a model organism:

  • Training: a self study-based Drosophila genetics training package including a comprehensive introduction to all basics and training tasks — (LINK)
  • I FLY BIO – Drosophila basics and genetic tools — (LINK)
  • Movies about Drosophila and fly research — (LINK)
  • Comparing fly and human organs — (LINK)
  • Lay articles about Drosophila research — (LINK)
  • History articles about Drosophila research — (LINK)

Education & teaching:

  • droso4schools biology lessons using Drosophila micro experiments — (LINK)
  • Strategies and resources for teaching Drosophila at schools and university — (LINK)
  • Genotype builder: a Powerpoint file to quickly generate images of flies with your own choice of marker combinations — (LINK)

Outreach materials and advocacy:

  • Collection of engagement resources for all kinds of purposes — (LINK)
  • Fly art gallery — (LINK)
  • “Why fly?” on droso4public: ideas and arguments — (LINK)
  • “Why fly?” on droso4schools: ideas and arguments — (LINK)
  • An advocacy article addressing politicians — (LINK and as GSA blog)

Websites:

  • Manchester Fly Facility (droso4research) / Training – resources that reach out to university students and scientists not working with fly — (LINK)
  • droso4schools – support site for school outreach and education resources of the Manchester Fly Facility, all using Drosophila as teaching tool — (LINK)
  • droso4public – collating useful links and information to support you during Drosophila advocacy and public outreach — (LINK)
  • Fly Indonesia – official site of the Fly Indonesia initiative aiming to establish Drosophila as a research strategy in that country — (LINK)
  • droso4Nigeria – promoting Drosophila in Nigerian universities and schools — (LINK)
  • droso4LatAm – promoting Drosophila in Latin American universities and schools — (LINK)
  • Drosophila Photography — (LINK)
  • Manchester Fly Facility YouTube channel — (LINK)
  • Manchester Fly Facility Resources 1 – mixed engagement resources — (LINK)
  • Manchester Fly Facility Resources 2 – Biology lessons for schools using the fruit fly Drosophila — (LINK)
  • Manchester Fly Facility Resources 3 – Resources for communicating Drosophila research in schools and on science fairs. figshare, m9.figshare.4262921 — (LINK)
  • #MelanogasterCTF – citizen science project in the area of population genetics — (LINK)
  • Drosophila Research & Training Centre – Drosophila outreach and training in Nigeria — (LINK)
  • I FLY BIO – Drosophila basics and genetic tools — (LINK)
  • FLYING THRU SCIENCE – insightful blog posts about fly research — (LINK)

To make the impossible possible: publishing experimental data from decades ago

Andreas Prokop Uncategorized

I am currently writing papers based on data obtained by people of my group that partly date back more than 15 years. Astonishingly, I can easily find and reproduce all of these data and feed them into GraphPad for state-of-the-art analyses and graph design. This is possible mainly because, from early on, we introduced simple standardised measures of data filing used by all members of the group.

A simple and transparent naming and identifier system:

DorothyBishop-Tweet
Data management is a general challenge that requires discipline and simple consistent rules that are easy to follow.

As shown in the image, each experiment has its own folder named starting with the date the experiment was initiated, potentially followed by a letter (if more than one experiment began the same day) and using hyphen and underscore consistently: “21-08-29A_”. This number code is the identifier for this experiment, and all documents in this folder (see below) will start with this date and number.

To quickly browse through experiments, all folders are situated in one “Experiments” folder (rather than subfolders that group experiments in subjective ways), so that they line all up by date and can be quickly scanned for content by using their concise experimental descriptors. To provide these descriptors, the folder names contain key information about the experiment using shortcut that is common to members of our group: e.g. “21-08-29A_Khc8Df_tub-Syt_ConA_3DIV” [Date/identifier_genotype (Kinesin heavy chain8/Df)_antibodies used (tubulin-Synaptotagmin)_primary neurons cultured on concanavalin A_for 3 days in vitro]. We usually perform two sets of experiments and, if consistent, pool the data; the second experimental folder of this pairing will contain the pooled analysis and is named accordingly: e.g. “21-09-13_Khc8Df_tubSyt_ConA_3DIV-POOL”. This naming system enables efficient identification of needed experimental folders in a matter of seconds.

DataStorage

A simple and transparent system of storing experimental information
Each folder contains an explanatory document with the same name as the folder. It has three purposes: (1) promoting proper planning of the experiment, (2) making sure the experiment has been properly executed and closed, and (3) ensuring that the experiment and its outcomes are understandable even years later. Our ‘blanco’ document contains the following items:

  • date/identifier: see above
  • rationale/objective: as a rule of thumb, we should never perform experiments we do not understand or do not agree to. In both cases we should engage in further discussion – before time is invested in vain. To this end, writing an experimental rationale/objective of 1-3 sentences is a good check point, and it provides a narrative that can be understood many years later.
  • Experimental specimens used, such as
    • genotype (how identified, what controls)
    • developmental stage
  • Experimental procedures, such as
    • culture procedures: e.g. citing the file name of the specific protocol that will be/was used (which is usually stored in a dedicated “Documents” folder, tracking changes that are introduce over time as different versions), but listing potential deviations from that protocol
    • primary/secondary antibody combinations including concentrations and animals of origin
  • Documentation, such as
    • storage information: e.g. slide box/slot numbers of slides, specific links to online repositories
    • image plates generated
  • Results: describing quality of the experiment, observations, statistical analysis, pooled analyses
  • Conclusion: as a rule of thumb, an experiment should never be considered finished without having drawn a clear conclusion: e.g. a clear outcome, the need to repeat the experiment with different parameters, or a clear reasoning as to why this approach does not work and the fundamental strategy needs to be changed.

The explanatory document is the centerpiece of each folder and is accompanied by all other experiment-related files, such as image files, Excel sheets, statistics documents etc. Importantly, all document names should start with the date/identifier! This will allow you to copy these image or data files into different locations (e.g. when preparing publications or theses) but having an easy way to refer back to their original source if further information is needed.

At The University of Manchester, we are in the lucky situation that institutional backup server space is provided, which is good practice that will hopefully become standard at all universities. Members of my group usually store their ‘Experiment’ and ‘Protocol’ folders on an external hard disc that can shuffle between work and home, but use FreeFileSync as a reliable and efficient open source software (providing automatic updates upon a one-off donation) to make regular backups to the external server. In this way, all members of the group have access at any time, can share results easily and leave them behind as their legacy when moving on to other jobs.

Extending this model towards student project supervision
To help students organise their work and facilitate communication during supervision, we have developed our data storage model further, in that students maintain a summary document. This document can be sent to me in preparation of supervisory meetings, and it helps students to maintain an overview of their project – hence to keep a clear mind and prevent sudden panic attacks of the “I do not have enough data for my thesis” kind. As I tend to tell students: “If you keep this document up-to-date, the results part of your report/thesis is mostly written, just needs to be arranged into a meaningful order.” The document is broken down into at least four parts:

  • Brainstorm: Any ideas that might arise, be it during discussions, under the shower, on the way to uni or during reading, should immediately be inserted as a bullet point into the brainstorm section. It is key to equip each item with a brief rationale (we had various cases where we could not reconstruct the idea behind an experiment) and key ideas how the experiment could be performed. In our supervisory meetings we usually go through this list and set priorities for next steps.
  • Ongoing: Experiments that have been started are entered here or dragged over from the Brainstorm list. The aim is to provide a quick insight into how things are progressing, such as providing the experimental identifiers of completed sets of experiments with a brief statement as to what the major outcome appears to be. This serves as a quick summary describing the state of ongoing work, so that supervisory meetings are less about reporting but more about interpretation and focussing on the next steps.
  • Completed: Once experiments are completed, including data pooling and a clear conclusion, they can be dragged into the ‘Completed’ section. Since data and thoughts about your experiments are fresh in your mind at this stage, this is the time to insert data from your experimental document and edit the results and conclusions in ways that can readily be used in the report/thesis. It is essential to always list the experimental identifiers, so that more detailed information can be easily retrieved from the respective experiment folder if required. At this stage, you could also bring all graphs to publication standard and potentially select representative images which can be stored, for example, in the experimental folder (but clearly indicating in the ‘Completed’ section where to find them). Performing these tasks at this stage may take you half an hour or hour, but should be more efficient than performing them during the final writing stage where you first have to re-introduce yourself to the data – apart from the fact that these tasks will pile up to a huge work load that distracts from the actual writing. If all experiments are prepared in this way, the section can evolve over time: different sets of experiments can be grouped into higher order statements, and by-and-by first sub-headings can be written. I have made good experiences with keeping all this info in bullet point format so that it can be shifted around and played with. Furthermore, it does not harm to insert relevant references at this stage (or even in the experimental document), saving you the effort of having to ‘re-discover’ them at a later stage.
  • Discussion: As is the case for experimental ideas in the ‘Brainstorm’ section, any thoughts (your own or from the literature), topics or problems that seem appropriate/helpful for the Discussion, should be listed as bullet points whenever they surface. Ideas come out of nowhere but are quickly forgotten, and it is a great feeling to have them saved as a repository to work from when reaching the writing stage. Important: never throw away any bullet points from the ‘Completed’ or ‘Discussion’ sections, but rather shift them into a spare section (I call it ‘Tidbits’). Those points might seem obsolete at a certain time – but could turn into an unforeseen gem that fills a crucial gap at a later stage.

I hope some of these thoughts are useful, and any suggestions are of course most welcome. Some people might regard this procedure micro-management, but I do not see it this way. Ownership of the process lies with the lab members, and it is an opportunity to optimise data management and supervisory communication. I can say from experience that these procedures, if adhered to with discipline, are enormously time-saving in the long run and guarantee transparency and accessibility for decades – so that data that would otherwise never see the light of day, will get published in the end. Notably, this system of data management is independent of any dedicated software, hence highly flexible to use. Furthermore, I have seen students panicking that did not follow this path, and others executing final experiments until a couple of weeks before their submission deadline, since they knew that things were under control.

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.

 

Matthew Cobb: What makes great biology?

Andreas Prokop science communication ,
This blog about a plenary talk given by Prof. Matthew Cobb (The University of Manchester) at the School of Biological Sciences symposium on Friday, 12 January 2018 was first published on The Node on 19 Jan 2018 [LINK]

 

Matthew Cobb is an inspiring advocate and communicator of science, in particular of biology. This is clearly reflected in his books and articles about the history of biology (and beyond), and his various radio programmes reflecting on past and contemporary science topics. Recent highlights are his book “Life’s Greatest Secret: The Race to Crack the Genetic Code” (shortlisted for the 2015 Royal Society Winton Prize for Science Books) as well as his BBC Radio programmes “Editing Life” (a well-balanced analysis of the opportunities and risks of the newly emerging CRISPR gene editing techniques) and ”Sydney Brenner: A Revolutionary Biologist“ (about the life of this outstanding scientist).

As a result of working on two BBC radio programmes and a project on scientific collaboration (supported by a Sydney Brenner Research Scholarship from the Cold Spring Harbor Laboratory), Matthew has been reflecting on what are the magic ingredients that produce great biology. The talk he presented at Manchester’s School of Biological Sciences Symposium on 12 January 2018 (see re-recording of this entire talk here), was an inspiring and enlightening summary of the key ideas extracted from this endeavour.

In his talk, Matthew first gave a definition of “great biology” which he proposes as “influencing our thinking about life, from nucleic acids to ecosystems, in ways that are long-lasting and opening up new perspectives”; he pointed out that these traits are “not necessarily associated with large grant funding, publication in ‘high-ranking’ journals or practical or therapeutic implications”. He then moved on to explain what he thinks the five magic ingredients are that promote great biology, illustrating each point with enlightening examples of scientists and anecdotes from the biology’s past (one of them about amateur scientists!) – always with a view to current practice, and providing inspirational advice for the future. Certainly, I do not want to spoil the watching of Matthew’s talk by giving away the concrete examples, but shall briefly discuss the fundamental ingredients that Matthew highlighted, mixed in with some of my own thoughts.

The first advice is to be early in the game. To be at the forefront of new developments or even being a trend setter requires vision, meaning the ability to recognise today what will be important tomorrow, but also living with the right mind at the right time. Certainly, the chances of being in the early game is helped by keeping an open mind for the bigger picture and unanswered questions, rather than getting lost in detail. And there are measures that can be taken to this end. For example “The encyclopaedia of ignorance – life sciences”, edited by R. Duncan and M. Weston-Smith in 1977/78, was an inspiring attempt to make renowned scientists of the time think aloud about the future of the various life science disciplines; and I could imagine that this was a great catalyser for curious readers to awaken their pioneer spirits. Another important means to foster a culture that honours forward-looking thinking, is to free time for, and take an interest in, true dialogue and discussion. For this, we also need to generate the right environment and opportunities, such as to ensure that all new buildings have informal social spaces where people can meet and discuss. But also, when reviewing manuscripts, we need to be open to new ideas so that they can develop – rather than brush them away with a tunnel view. In a recent case of a fellowship application I experienced, ten lay reviewers gave maximum marks; in contrast, three specialist reviewers rated the application as being mere average, mostly based on technical detail and blind to the concepts and ideas behind that application and its potential to develop great science. It is the latter that we all need to recognise and foster.

The second advice is to think and plan long-term. Key to this strategy is the art of long-term objective setting guided by fundamental questions and their break-down into medium and short-term goals that can be dealt with at a time. Again, this is not made easy in the current science and science funding landscape, but all arguments are in favour of long-term developments. The “skimming-the-cream-and-moving-on” mentality might be good for the careers of individual scientists, but perhaps not so good for the actual science. Similar conclusions are drawn by the article “How should novelty be valued in science?” published by B. A. Cohen in Elife last year. Cohen’s analysis of arguments from the philosophy of science (how reliable knowledge is generated) and from the sociology of science (how science communities work most efficiently) clearly dismantle the excessive demand for novel mechanisms (as opposed to gradual development of concepts) that governs contemporary science funding and publishing policies. This trend has become a significant inhibitor of high quality science, and the alarming increase in reports about non-reproducibility of published results is a logic consequence of these developments, and poses a risk to the future of science.

The third advice is to choose and/or develop the right tools. Apart from the examples Matthew mentioned in his talk, I can mainly speak for the biomedical sciences; my personal experiences lie with Developmental Biology and Drosophila research within, both of which are under threat by the growing emphasis on translational (i.e. clinical) research. Many politicians and funders seem to focus increasingly on the final steps of the discovery pipeline, fixing their gaze on expected short-term returns. They overlook, and often don’t understand, that longer-term basic research (which is typically not performed on humans but on animal model organisms as the more versatile “tools”) generates the creative pool of ideas that will feed the bench-to-bedside pipeline in the future. But even within fundamental research, “tool choice” has shifted away from the use of genetic invertebrate model organisms, such as C. elegans or Drosophila, to the use of mouse models. This development fails to recognise that research concerning evolutionary conserved processes and mechanisms is done far more productively and economically in the smaller model organisms; as Hugo Bellen once stated [LINK]: “You get 10 times more biology for a dollar invested in flies than you get in mice”. I therefore believe that we would see greater biology if grant panels looked more critically at the justifications for the model organisms that are being proposed for projects – and that such a practice would free up funds for a greater variety of science.

The fourth advice is to build good teams. Matthew highlighted three factors. Ideally have at least one person with great vision in your team that has the genius to drive the conceptual ideas behind the work. Be complementary in your expertises. But, most importantly, foster a productive culture of discussion: be prepared to play around with ideas even if they appear mad at first sight; and enjoy and capitalise on friction coming from different opinions and opposing thoughts, so that the best ideas can emerge and be developed into scientific experiments.

The fifth ingredient, least accessible to advice, is luck! We all know this component as a potential maker and breaker of careers. This said, bad luck certainly breaks those who either lack the vision or disregard the above advice. However, the good scientists will be prepared: either by taking the long view that provides flexibility for alternative strategies and approaches, or by using failure as an opportunity to rethink and take new directions – perhaps providing a new chance to be early in the game! As Napoleon supposedly said: “I believe in luck, and the wise man neglects nothing which contributes to his destiny”.

But even if we are eager to follow this advice, the circumstances of the current science landscape might not be in support of great biology. Harmful metrics, counterproductive expectations, bureaucracy, a shift in public opinion, and harmful publishing policies “bully us into bad science” and promote self-focussed communities and mechanisms that inhibit true progress and passion for science. Some examples were given above and many more can be found in other publications (e.g. Lawrence; Cohen; Young; Smaldino; Martínez-Arias; Nerlich). But, as I argued in a recent blog, we must organise ourselves and engage as a community in dialogue with each other, clinicians, policy makers, funders and publishers – all with a view to improving the biology we do. For such dialogue, we need arguments and elevator pitches that are engaging and convincing. To this end, Matthew’s talk is a rich resource of ideas and well thought-out arguments that we all should listen to and take on board.

Andreas Prokop

Watch his talk: