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Scanning micrograph of an apoptotic HeLa cell Cell spotting – let’s fight cancer together!

“Tell me and I forget, teach me and I HeLa cells may remember, involve me and I learn,” HeLa cells are a special hu- Benjamin Franklin once said. Make that man cell line. They originate from a woman called Hen- quote yours and involve your students in a rietta Lacks, who died from cervical cancer in 1951. Her real cancer-research project that will teach doctor took some cells from them more than just genetics and cell death. her tumour and managed to grow them in a culture me- dium, developing the first human cell line. HeLa cells By António J Monteiro, Cândida cells without harming healthy cells. are the most widely used G Silva and José C Villar Existing chemotherapy treatments human cells in biology labs have failed to reach that ideal level of

BACKGROUND across the world. fficient cancer drugs need to selectivity, but many research teams E selectively destroy tumour continue to look for compounds that 46 I Science in School I Issue 31 : Spring 2015 www.scienceinschool.org Teach

could become the effective and side- the response of HeLa cells to different Biology effect-free drugs of tomorrow. chemical compounds. Biology The search for suitable compounds The Cell Spotting project is performed primarily by robotic Ages 14–18 The Cell Spotting team is testing systems that quickly test and identify This article describes a stu- more than 14 000 chemical com- millions of candidate chemical com- dent-centred activity that pounds in HeLa cells and observing pounds: they put cancer cells together introduces the concept of their reaction using advanced optical with potential drugs and observe efficient cancer drugs and microscopy techniques. HeLa cell cul- whether the cells die or survive. Such how different compounds tures are being photographed every experiments generate thousands or are tested to see if they are Image courtesy of the National Institutes Health (NIH) half hour in three different channels: even millions of cell images that then effective in killing cancer normal , blue and green fluores- need to be analysed according to cells. Students are then led cence (Lostal et al, 2013a; 2013b). The several parameters – such as the cell’s through an exercise in which normal light reveals the global shape status, the release of cellular content, they learn about HeLa cells of the cell membranes; the blue fluo- the distribution of the mitochondria, and how these are cultured rescent channel is specifically for the or the shape of the nucleus – and clas- with isolated compounds to observation of the cell nuclei (they are sified to determine the cell’s response test the effect of that com- dyed with the fluorochrome Hoechst to each potential drug. The ideal solu- pound on cancer cells. They 33342, which emits blue light when tion to treat this huge amount of data also learn about cell apopto- bound to DNA); and the green light sis and cell necrosis through would be to use computers. However, is for the observation of the cells’ mi- visual examples. they are not good enough to recognise tochondria (which are dyed with the patterns: nothing beats the human fluorochrome Mitotracker). By com- Students are then introduced eye for that task (Lostal et al, 2013a; bining data acquired from the three to the Cell Spotting research 2013b)! channels, the scientists can generate project, which allows par- That is where you and your class images that contain detailed informa- ticipants to analyse cells and step in. Researchers need help from as tion about these three elements of the contribute to the project by many volunteers as possible to sup- cells’ structure and also videos that uploading their analyses. port them with image analysis and to show cell movements, division and Each step of the project is identify potential new drugs against death over time. More than 4000 im- supported by clear instruc- cancer as rapidly as possible. Your ages are taken per day and about 14 tions and explanatory notes students will learn about cell death 112 images are produced in a single to help students use their by helping scientists to characterise experiment. knowledge and contribute to the project.

REVIEW Dr Shaista Shirazi, UK Image courtesy of SOCIENTIZE

Figure 1. Comparison of an animal cell representation with a HeLa cell image

www.scienceinschool.org Science in School I Issue 31 : Spring 2015 I 47 Spot cells and help fight Procedure necrosis and to identify healthy cancer from your classroom HeLa cells from dying cells: A) Explore the Cell Spotting research a) Ask your students to analyse This activity is designed to be imple- project and understand its context. figure 5 from the didactic unit mented in biology courses for stu- In the first part of the activity, stu- and to build a table similar to dents aged between 14 and 18 years dents should use enquiry-based think- table 1 to summarise the main old, however you can also adapt it for ing to learn about the research project morphological differences other groups. It explores themes such and its methodology. between the two types of death: as cell division, cell death, genetic w1 1) Watch the video ‘Socientize: Cell cell volume differences, nucleus regulation, cancer and biotechnology. Images Experiment’ to place the condensation and final ­reaction. The activity is divided into two parts: activity into the right context. b) Watch the three short clips 2) Go through the didactic unitw2 and A) Explore the Cell Spotting research showing HeLa cells in different find the answers to the following project and understand its context, states (healthy, in apoptosis, questions: and in necrosis) from the teacher’s B) Play with the Cell Spotting applica- a) What is José Villar doing in his package. Ask students to iden- tion. research? tify which cell state is repre- b) What type of cells is he using? sented in each short clip based Materials c) What methodology is he using on the morphological differ- The resources available for this activ- to observe the cells? ences. d) What results can he expect ity are: Now your students are ready to help w1 from different chemical com- · a video that puts the Cell Spotting José identify HeLa cell images! pounds? research project into context B) Play with the Cell Spotting e) What type of cell death does · a didactic unitw2 that provides a ­application. José Villar want to induce in potential lesson plan and activities w4 cells? Why? The Cell Spotting application allows to do with students you and your students to analyse · a teacher’s packagew3 that contains At this stage, it may be useful to build HeLa cell images and send your a detailed document about the a simple diagram like the one shown analysis to the research team. The research, a PowerPoint presentation in figure 2: application interface is very intui- and three short clips about HeLa 3) Show your students how to dif- tive, user-friendly and self-contained, cells. ferentiate between apoptosis and so everybody can easily access and

What is being tested?

> 14 000 chemical compounds In what?

Live Cells Image courtesy of SOCIENTIZE HeLa Cells What to expect? (cancer cells) How many types? Dead cells Apoptosis

Necrosis

Figure 2. Example of a diagram to explore the Cell Spotting experiment

48 I Science in School I Issue 31 : Spring 2015 www.scienceinschool.org Teach

Image courtesy of SOCIENTIZE

Apoptosis Necrosis Biology Table 1. Example of a Cell volume Decrease Increase table summarising the main morphological differences Cell nucleus Fragmentation after condensation Volume increase between apoptosis and necrosis Content release No (formation of apoptotic bodies) Yes

Inflammatory response No Yes

contribute. When you access the ap- plication for the first time, we recom- mend that you follow the tutorial that explains its structure, objectives and resources. This will ensure that you have all the necessary details before you log in and start spotting and tag- ging cells with specific stamps. To complete each task, you need to analyse the same image according to four parameters: · Current cell status (dead or alive) · Cell content release (whether the cell releases material or not) · Mitochondria distribution (whether the mitochondria are clustered or Bortoletto Image courtesy of Juliana scattered inside the cell) · Other remarks (e.g. multinucle- ated cell, abnormal sized cells and nuclei) 1) Ask your students to log in the application and register so their contributions do not remain anonymous. 2) Explore the application with your students and define exactly what they should do. If you have a pro- jector, this can easily be achieved by doing a cell image analysis together while projecting it on a wall. In a nutshell, the application in- cludes: · the blue bar (see A on the image) on the top, which summarises what you need to do and the resources to achieve that task, including: Figure 3. Representation of cell death: apoptosis and necrosis www.scienceinschool.org Science in School I Issue 31 : Spring 2015 I 49 Image courtesy of SOCIENTIZE

Representation of cell death: apoptosis and necrosis

Figure 4. Cell Spotting application

· the specific question that you The image awaiting analysis is in box can finish the task. After that, a new need to answer B (in figure 4). Below it you can find image will automatically appear and · the three different light the various stamps to tag the cells you can start the analysis all over. channels that you can use to and identify their state (see point 8 on NOTE: A guide to get started with visualise specific details on the Fig. 4). You can also remove the tags Cell Spotting is available in the image: blue to visualise the individually (see point 10 on Fig. 4) teacher’s package. The analysis is very nucleus; green to view mito- or start over (see point 11 on Fig. 4). simple and your students will prob- chondria; and normal, which If you are not sure how to classify the ably do it easily. is a result of the blue, green cells, you can use a specific tag with 3) Let your students play with the and bright white field images a question mark (see point 9 on Fig. 4). programme and contribute freely. merged Box C provides you with a set of Let them know that they can also · the video from which each im- examples of the patterns that need to log in from home. age was extracted be identified. · additional information on each Finally, below the image for analysis, step you will find a progress bar with the four parameters that you need to com- · access to Vish, the Virtual plete for each task (see box D in figure Science Hub, an educational 4). Every time you finish analysing a platform where you can virtually parameter, you must click on the ar- visit the lab where Cell Spotting row to the right of the progress bar so takes place you can move to the next parameter. · a feedback survey When the four parameters have been · a direct link to the didactic unit analysed, an icon will appear so you

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m I project Socientize from its official official its Socientize from project . You website: www.socientize.eu citizen science will also find other that you can get involved projects in. by Socientize, promoted projects the website of consult the official www.ibercivis.com project: Ibercivis see: activity, Communication and Public Engage- ment team (2010) Can you spot a cancer mutation? Science in School 16: 39–44. www.scienceinschool. org/2010/issue16/cancer nce in School Science in School Resources about the EU-funded Find out more of citizen science keep track To teaching For another cancer-related - the Cell Spotting activity: the Cell Spotting activity: - in English: www.ibercivis. net/?p=6985 - in Spanish: www.ibercivis. net/?p=6987 - in Portuguese: www.ibercivis. net/?p=6989 contains a de- Cell Spotting activity tailed document about the research, the Cell Spotting guide, a version of the didactic unit with solutions, and health short videos of different three down can You states of Hela cells. load it here: - in English: http://bit.do/ ibercivis_teacherspackage - in Portuguese: www.ibercivis. net/?p=6993 application and start playing, visit the Socientize website: https:// pybossa.socientize.eu/pybossa/ app/cellspotting/ w2 – Download the didactic unit for the didactic w2 – Download package for the w3 – The teachers’ access the Cell Spotting w4 – To - Images Experiment’ video on channel: YouTube Ciencia’s Ibercivis - in English: http://youtu.be/ XXegth8CmM4 - in Portuguese: http://youtu.be/ OGTITEp-ybI Martínez P, Sanz F, Val C (2013a) Val Sanz F, Martínez P, as a Case of Analysis Cell Images Advanced Edu Citizen Science for cation: Laboratory and School, Back cation: Laboratory of the 7th and Forth. In Proceedings Education International Technology, (INTED and Development Conference : 2013) pp 2489–2496. Valencia, IATED C (2013b) Val Sanz F, Martínez P, for case of Citizen Science A Analysis. In Cell Biology Images of the XXXIII Congresso Proceedings da Sociedade Brasileira de Computação (CSBC 2013) pp 1855–1862. Maceió, Brazil: CSBC Students working on Students working a class assignment in the computer lab

w1 – Watch the ‘Socientize: Cell the ‘Socientize: w1 – Watch Web references Web Lostal E, Serrano F, Carrodeguas JA, Carrodeguas Lostal E, Serrano F, References Lostal E, Serrano F, Carrodeguas JA, Carrodeguas Lostal E, Serrano F, einschool.org www.scienc Image courtesy of By GerryShaw/Wikimedia

socientize.eu. Her current scientific HeLa cells grown in tissue interests focus on machine learning, culture. Red: cytoskeleton; António Monteiro is a biologist with data mining, drug discovery, citizen green: nucleus an MSc in biology and geology teach- science, e-science, volunteer comput- ing. He is actively involved in the ing and data warehousing. citizen science FP7 project ‘Socientize José Carrodeguas Villar, PhD, is a – Society as e-Infrastructure through researcher at the Institute for Bio- technology, innovation and creativ- computation and Physics of Complex ity’. He has worked for the Science Systems (BIFI) at the University of Museum of the Zaragoza in Spain. He leads a research in since 2009 as an exhibi- group focused on the study of apop- tion guide and education developer tosis in cancer, the immune system, of science activities, mainly for the nervous system and other systems. Researchers Night. He is also involved He is also the principal researcher of in promoting the museum via social the Cell Spotting experiment and is media. actively involved with citizen science Cândida G Silva holds a degree in projects and activities at Socientize mathematics and computer sciences and Ibercivis. and a PhD in chemoinformatics. Dur- This is an activity proposed by ing the past four years, she has been Socientize, a project funded by the an active collaborator of two citizen European Union Seventh Framework science and Programme under contract RI-312902. projects: ibercivis.net and

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