Funny Game Intro: Microbot: Good Morning! Player’s choices: Good morning to you, Microbot. It’s not morning any more! It is midnight, silly Bot! You are docked in a tiny vial, in a cabinet in a lab: you have no idea what time it is outside! Microbot: I love mornings! Microbot: OK, Pilot. Our last mission did not go so well. Player’s choices: I’m sorry!! It was an accident, Microbot. I have studied, I now realize that Macrophages eat foreign objects, including Microbots!! It wasn’t my fault. Your fancy flagella motor let us both down! Microbot: No matter. I have created the ultimate training device for you. The most brilliant way to teach is through a game, your relative, Plato said that. Player’s choices: Not all humans are related, Microbot. You are designed to function inside humans, not study our history. I grew up pretty far from Greece, tiny Bot. Stay on topic, Micro-Know-It-All. Microbot: I have created, Immune Defense. I have used data from real cells to create a set of cells you can control. You won’t understand what cells are doing until YOU try to do it for them! Player’s choices: Thank you, Microbot! Let’s get started! I am supposed to be learning your controls, not studying Immunology! This Immune Defense better not be a waste of time. I think you underestimate my driving skills, Bot. Microbot: Immune Defense will teach you how cells move, communicate and fight off pathogens. You might finally learn the difference between a bacterium and a virus! The Mission Intel Database will always contain information about the cells, molecules and pathogens you encounter. Microbot: Molecules Microbot: Well, start the game! ((Button Blinks)) Note to teacher. This intro is not included in this demo. Our development tem could not decide whether to use it. You could show it to your students and let them debate whether they would use it… and perhaps suggest how they would convey the same information in a more fun format. Information we wanted to convey: Player is a pilot of a Microbot. The Microbot created this game. The Game requires you to use the Microbot’s controls to play. Potential design flaws of this conversation: The player may feel alienated because the Microbot does not appear to listen. You can always send your feedback to us at mstegman@FAS.org. We’ll add you to our credits. Thank you! Melanie Stegman, Ph.D. Learning Technologies Federation of American Scientists This is the text from the first Tutorial card: Introductory Movie Script…… White blood cells track and kill pathogens. Without eyes, working in teams, spread out over our whole body, the Immune System is a powerful killing force. It must be very carefully controlled. I built Immune Defense on data from real cells. The White Blood Cells in the game move and respond just like real White Blood Cells. You will control them. You will demonstrate your understanding by winning the game Immune Defense. To control White Blood Cells, you will need to see the Molecules. Molecules are 1000 times smaller than cells. Molecules are proteins on the White Blood Cell Surface. Molecules are proteins that show where Pathogens are. Molecules allow white blood cells to perform very complex behaviors. Immune Defense is built on real molecular data, too. Molecules always move randomly. See the millions of molecules, watch their random, thrashing Brownian motion. Immune Defense shows symbols in the place of molecules. Spend energy to move molecules. Change the receptors the White Blood Cell surfaces. Demonstrate that you understand the complex killing machine. Play Immune Defense. Upgrade questions: Teachers, you can use these questions in class to find out for yourself whether your students learned the answers… The idea is that after each level is over, or whenever the player wants it, these questions and answers help the player define what they have learned. … so the gameplay is not interrupted by explanations but we all feel smarter after playing. What do you think? Questions Level 1 Microbot: What kind of cell are you controlling? Player’s options A Neutrophil A White Blood Cell A Phagocyte All of the above Microbot: Excellent! (All answers are correct, this is just a demo so far…) Microbot: What are these ((Picture of GreenLPS Receptors))? Player’s options Proteins Receptors E coli binding tool All of the above Microbot: Excellent! Microbot: Your answers demonstrate that you know that Proteins are tools that cells make. In particular, you know that White Blood Cells use LPS Receptors to bind to the LPS on bacteria surfaces. Questions Level 2. Microbot: What are these ((PurpleC)) Player’s choices: Proteins Signal molecules Complement proteins All of the above Microbot: Excellent! Microbot: What is diffusion? Player’s choices: Random motion of particles in space The reason signal clouds are useful What molecules do if no other forces act on them All of the above Microbot: Excellent! Microbot: How can a cloud of proteins lead a White Blood Cell to bacteria? Player’s choices: Chemotactic behavior is what we call moving according to a Chemical gradient One bound PurpleC receptor causes the WBC to move forward… It is mathematically more likely to come across another signal, if it moves in the direction of the source All of the above. Microbot: Your answers indicate that you have learned that PurpleC is a protein that diffuses through space, forming concentration gradient and leading the WBC to the source of the infection! Microbot: You now have access to the Molecular Manipulator’s PUFF function. When PUFFing, the molecular manipulator uses energy to move molecules away from the center of the circle. Questions Level 3 Microbot: Why does my PurpleC Receptor not always bind to PurpleC? Player’s Choices: PurpleC and its Receptor have a low affinity interaction PurpleC bounces into its Receptor often, but it does not often find the correct orientation Non-specific interactions among molecules are common but specific binding is a unique, happy and sometimes rare event! All of the above Microbot: Excellent! Microbot: What causes the PurpleC to bind or not bind its Receptor? Player’s choices: The shapes of the PurpleC Receptor The shape of the PurpleC The number of times the PurpleC and its Receptor bounce into each other All of the above Microbot: Excellent! Microbot: From your answers to my questions, it appears you have learned that molecules bounce into each other often. Every now and then a specific bond occurs when the shapes of two molecules match and they also hit it other at just the right angle … and binding happens. Microbot: Now that you understand affinity, you can make use of the Molecular Manipulator’s Multi Molecule function! Summary of each level: 1 STAGE 1 Neutrophil eats E. coli with LPS Receptor, and follows PurpleC cloud with PurpleC Receptor. Molecular Manipulation not necessary, and not introduced. LEARNING OBJECTIVES Neutrophil is a White Blood Cell Neutrophils (and all cells) have proteins on their surfaces Neutrophil uses Green LPS Receptor to bind and eat E. coli Neutrophils needs a different protein on its surface to move closer to the E. coli Proteins each do unique things. ((Datacards 1,2 3, 4)) STAGE 2 Player must drag PurpleC molecules with Molecular Manipulator LEARNING OBJECTIVES The E. coli is causing a Complement signal cloud. Neutrophil can “follow the cloud” by always moving toward a Complement Protein when it binds to one. Molecules always move randomly! To stop the random motion and control it, we need Energy. Molecules have kinetic energy. Molecules move in Brownian Motion = random! A containment field must exert equal and opposite forces to stop molecules = Energy required. Signal Cloud is a “Concentration Gradient:” as we move toward on signal we become ever more likely to encounter more signal. ((Datacards 5,6,7)) STAGE 3 Player must lead the Neutrophil around hunting E. coli. LEARNING OBJECTIVES Bumping into each other is something molecules do every femtosecond. Having a specific interaction is a very special situation! Affinity is a measure of how well a signal specifically sticks to its receptor PurpleC is low affinity, which means it binds its receptor specifically not very often and not very long. Molecules fumble when the meet and Bind with they have specific interactions. ((Datacards 5,6,7)) STAGE 4-7 Player must lead the Neutrophil, buy more Neutrophils, hunt down E. coli and “low complement bacteria, called Streptococus, that does not let the human body’s Complement proteins bind to it as well. . LEARNING OBJECTIVES Bumping into each other is something molecules do every femtosecond. Having a specific interaction is a very special situation! Affinity is a measure of how well a signal specifically sticks to its receptor PurpleC is low affinity, which means it binds its receptor specifically not very often and not very long. Teachers, this is a sketchy description of the text on each of the tutorial slides. This is for your reference… see what words we used, etc., to help you gauge how much students are picking up by playing. Additionally, these cards explain how to play the game. Tutorials: 1. Controls 2. White Blood Cells 3. Receptor Menu 4. Molecular Manipulator 5. Action Points 6. Affinity 7. References 1 Welcome to Immune Defense. “Controls” is pop up title You are controlling me, your Microbot, from your human sized Cockpit, as usual. But today I am showing you a projection of a game I made for you. Use these controls in your cockpit: Molecule Manipulation: GRAB a molecule: Left Click and Hold. Drag to new position. PUSH a molecule away: Right Click on a Molecule. Protein Regulation: CHOOSE which proteins to put on a Cell surface: Right Click on a Cell. Microbot: LOOK around: Arrow Keys or WASD. UPGRADE your Microbot controls occasionally, click on Upgrade button. 2. White Blood Cells White Blood Cells, or WBC, are your tools against Pathogens. There are many different kinds of WBC. Every cell in a body has the same DNA, so every cell could make the same proteins. But instead, cells each make a unique set of proteins. Therefore, all cells have different unique activities. Human cells have about 26,000 genes (which code for proteins). You will regulate the proteins “expression.” This means you will CHOOSE whether or not the proteins are on the surface or not. But you will only regulate the expression of three kinds of proteins: 3. Receptor Menu Same text as is, except last sentence: The regulation of protein expression is your responsibility now! 4. Molecular Manipulator ((Keep Image)) To GRAB a molecule: Left Click and Hold. Drag to new position. New ways to manipulate molecules will be granted in the upgrade menu, when concepts have been mastered. ((Image of Upgrade button if you want one)) 5. Action Points. All New Text: Energy is represented in this game by Action Points. Molecular Manipulation requires Energy: one Action Point per Manipulation. Action Points are also required to buy more Cells. Earn Action Points by destroying Pathogens. Action Points will accumulate come slowly over time. Molecular Manipulator. Each Action Point is worth 10 score points at the end of each level. I will display the current tally of Action Points above the 6. Affinity New Text: A low affinity receptor-signal pair do not bind well. You are seeing the PurpleC Signal fumble around and only bind its receptor about every third time. They are a low affinity pair in this game. Later, in Immune Defense you will meet find high affinity pairs of molecules. ((Image label: This is an “LPS Receptor in real life. It is called a “Toll Like Receptor or “TLR. Light blue = Receptor Green = signal.))) 7. Items in Immune Defense Purple Complement Protein = PurpleC ((image)) After the whole C5 protein sticks to the bacerium surface, a part of it, called C5a, breaks off and becomes a signal that moves randomly around the bacterium. PurpleC Receptor ((Image)) This protein is expressed by Neutrophil cells and binds to the PurpleC (C3a) protein signal. The receptor’s other end is inside the cell. The receptor changes shape when it binds to its signal. The shape change causes many other proteis to change, which causes the cell to move! GreenLPS ((Image)) LPS is a big molecule that is part protein, part lipid and part sugar. This odd molecule is only found on Bacteria surfaces. Because Neutrophils are powerful killing machines, it is good that they bind to a very off molecule that is only found on bacteria! GreenLPS Receptor ((Image)) This protein is expressed by all WBC in the Eater class. This receptor is called TLR-4 and without it we would have a weak innate immune system. TLR4 has a rich history. It is evolutionarily related to the Toll Receptor which was first found in fruit flies. Toll is German for “Cool.”