National Science Education Standards Addressed in this Unit: LSCell1 LSCell2 LSCell3 LSCell4 LSEvol1 LSInter3 LSInter5 LSMat4

LSGene1 LSGene3 UCP1 UCP2 UCP5 SI1 SI2 ST1 ST2 SPSP1 SPSP4 SPSP5 SPSP6 HNS1 HNS2 HNS3 Cells have particular structures that underlie their functions Most cell functions involve chemical reaction Cells store and use information to guide their functions Cell functions are regulated Species evolve over time Organisms cooperate and compete in ecosystems Human beings live within the worlds ecosystems The complexity and organization of organisms accommodates the need for obtaining, transforming, transporting, releasing and eliminating the matter and energy used to sustain the organism In all organisms, the instructions for specifying the characteristics of the organisms are carried in the DNA Changes in DNA (mutations) occur spontaneously at low rates Systems, order and organization Evidence models and explanation Form and function Abilities necessary to do scientific inquiry Understandings about scientific inquiry Abilities of technological design Understandings about science and technology Personal and community health Environmental quality Natural and human-induced hazards Science and technology in local, national and global challenges Science as a human endeavor Nature of scientific knowledge Historical perspectives

Dear Class of 2013-14, Welcome to your new classrooma biosafety staging lab where youll have the opportunity to manipulate and experiment with viruses each day! Thanks to the generosity, ingenuity and cooperation of several scientists in the Molecular Microbiology and Pathology & Immunity Department at Washington University, specifically Dr. David Wang, you will have the opportunity to work on a new research project involving viral infection and eradication and the development of immunity. Dr. Wang and his team have volunteered their support to our project and I hope that as we embark on this journey together, youll consider gifting your research and results to Dr. Wang to be an end-goal for this unit, because I know your reports will prove useful for future research. In addition to working with organisms and testing hypotheses about viruses, well be studying how viruses infect people, how they survive, how our bodies fight them and how science has evolved to combat them through vaccines and drugs. Youll have the opportunity to do an indepth case study on one specific virus and its mechanism for reproducing, and as a class, well explore the human immunodeficiency virus and its implications. We will read a true account of an Ebola virus outbreak which occurred in Northern Virginia twenty years ago, and how scientists and soldiers fought to contain it. Youll also have the chance to choose or design a project that appeals to you which gives back to the local community in some aspect relating to viruses. But we will get to that when the time comes! For now, begin to think about what you know about viruses and what youd like to know about them. One note, it is very important to me that every student feels safe and empowered in this space. If at any time during this unit you feel anxious, stressed or uncomfortable, please feel free to talk to me, and we can meet to discuss your concerns or confusion. Sometimes fears or uncertainties can hold us back from doing our best and being our most curious selves. During this unit, I hope you will think about how you can challenge yourself to go beyond those fears or uncertainties, because science is all about designing and testing and using the results to inform our subsequent designs. Sometimes perceived failures are actually great successesjust like chocolate chip cookies, right? So snap on your gloves and pop on those goggles; these viruses wont eradicate themselves! Or will they? See you in the lab,

Challenge Board
Create a comprehensive, yet readerfriendly timeline of HIV/AIDS including all relevant scientific, political, social and economic developments. Check out Frontlines The Age of AIDS timeline: http://www.pbs.org/wgbh/pages/frontline /aids/cron/ for ideas before you begin. The CIA Factbook also gives timely statistics on AIDS deaths and other demographic information. Volunteer at a Non-Governmental Organization that seeks to help people infected with HIV; ask if you can interview an employee or participant; write a one page summary of your experiencewhat did you see? What did you do? Who did you talk to? How do you feel like you helped while you were there? The Good, the bad and the Ugly?: Research the response of an NGO, a for-profit company (think drug company) or a government organization (suggestions: WTO, WB, IMF, USAID) to the HIV pandemic. Critique what the institution has done well and what it could improve or could have improvedpresent as a video, rap/song, paper or another creative way According to the WHO, standard anti-retroviral therapies involve the combination of at least three anti-retroviral medications; investigate a traditional treatment regimen, and present how the medicines work, how much they cost and design a treatment plan describing how and when they should be taken Create an educational brochure for middle school students about HIV prevalence, spread, mechanism, etc. Create a worldwide map of HIV/AIDS, somehow showing where it is found and in what concentration Propose a theory for why it looks the way it does Research the Tuskegee syphilis experiments and research some of the trials of antiretroviral medications in Africa. Compare and contrast or critique in a one=page paper. Courtney, these challenges are nice and all, but Id really rather do my own: heres my idea.

Watch Deadly Catch and Thailands AIDS warrior and write a one page summary comparing and contrasting the two. What are your thoughts on each?

Week 1, Day 1
The Motion of the Ocean
(Discrepant Event/Warm-up Activity)
Begin by giving each pair of students a one liter bottle of water from the ocean, and asking them to write continuously for two and a half minutes everything they can about the water using their senses. Consider playing wave sounds or underwater music if you can. Inform students when thirty seconds remain so that they have a chance to conclude their thoughts. After the free-write, ask students to listen to the following brief story 1:

Zimmer, Carl. A Planet of Viruses. University of Chicago Press, Chicago: 2011. 4

Optional (if students are engaged, and you think its relevant to connect to humans, you could continue with the next two paragraphs:

Returning to the seawater in your jar, what do you think of it? How many viruses do you think it contains? Take some guesses, find out why? More or less than the cave? Why? Every liter of seawater contains ~one hundred billion viruses. Viruses outnumber all other ocean residents about fifteen to one. That doesnt mean swimming in the ocean will make you sickonly a minute fraction of them could infect us. In 200 liters of seawater, scientists typically find 5,000 genetically distinct kinds of viruses. Microbial interactions, seen in the photo at the left, between oceanic viruses (small dots) and bacteria (larger ones), take place on the nanometer scale but are extremely important in the cycling of nutrients like carbon, nitrogen and phosphorus in the world's oceans. (Credit: Rachel Parsons2)

So, what do you want to know about Viruses?

Futurity.org, 10 Million Viruses in One Drop of Seawater. http://www.futurity.org/earth-environment/millions-ofmarine-viruses-ebb-and-flow/
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Lead a think-pair-group share activity, giving students 3 minutes to write their own questions, 3 minutes to work with a partner to generate new questions, and then a room sweep, where each pair takes turns sharing a yet unrecorded question. Stop when you fill up the chart paper, or when students run out of original questions.

Anticipation GuideTrue or False

The common cold is caused by bacteria Viruses are living, like parasites People can create viruses through certain behaviors You can catch an illness from your dog Vaccines protect you from getting the flu HIV kills people every day There is an HIV cure True True True True True True True False False False False False False False

Can Worms Cure HIV?

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We all know that worms crawl in and that worms crawl out, sometimes they even play pinochle on your snout, but can worms teach us anything about how to eradicate viruses? Dr. Wang, who you will get to meet in a few days, helped to author a recent study about a special worm named C. elegans which is ideal for studying the way viruses and hosts interact. Before this study no one knew C. elegans became naturally infected by viruses. The virus that attacks C. elegans destroys its intestinal cells integrity, which causes a visible change in the worm that you can see under a microscope. Because these worms mature and reproduce so quickly, they are great for studying viruses and the ability to develop immunity over generations. In one month, C. elegans can produce up to 10 generations! So, in this unit, you will be able to produce what would take people about 250 years to create!

Dr. Wang and I discussed the work the 2012-13 class did with C. elegans, and he is very excited to partner with us in this project. He is grateful to have twenty young scientists to help him do research, and hopes that you will present your findings to him in a months time. Usually, when research assistants work for professors, the assistants have to do whatever the professors tell them to, including getting their coffee, volunteering to test out new procedures, writing emails to their OKCupid favorites or trying to break into their houses to feed their pets when they miss their return flights from vacations But Dr. Wang is the best prof ever! Hell never make you order him a half-caf, soy latte peppermint macchiato AND hes letting us choose what we want to research! He wanted me to let you know that he has many ideas for projectseven just repeating his own experiment to verify the findingsbut he really 8

wants you to choose a research topic which appeals to you .

Dr. David Wang, Head of Wang Laboratories

After brainstorming ideas and then negotiating a choice with your partner youll need to write up a proposal for your research project. In addition to testing some aspect of how viruses and hosts interact, your proposal needs to: Be affordable (less than $50 per pair) Be time-conscious (able to be achieved in about one month) Involve at least three generations of worms Get outt Dr. Wang has given us many organisms to experiment with, but only a limited amount of virus. The virus occurs naturally in France, and is called the Orsay virus (as viruses are usually named after the place where theyre discovered). Given our limited quantity of virus and a desire to be equitable to all partners, everyone will receive an equal, small quantity of virus (called a 0.2 nanometer filtrate). Additional filtrates can be earned by winning challenges throughout the unit or as a gift from another lab group.
here!

Week 1, Day 2: Mini Challenge #1: Design and Infect

Before you and your partner begin to design and propose your experiment, were going to practice infecting the worms, as it will be a useful tool to have at your disposal throughout this month. Recall that we have a limited amount of virus (each pair will receive a filtrate measuring approximately 0.2 nanometers). Your challenge is to work with your partner to design a procedure for infecting your nematode with the Orsay virus. Think about how viruses spread. Begin brainstorming now, and record a rough draft of your procedures for infecting your nematode, C. Elegans. Procedures should be easy to follow and in numerical order.

Just like Jackalopes?

Mini-lecture on virus transmission (see attached PowerPoint for slides) Notes for lecture accompanying slides: The year is 1930 and ranchers and farmers alike in the Southwestern US are in a panic. Was it 9

retribution for their excesses during the Gilded Age? Was it God smiting them for their lack of faith? What could have caused this hideous, hungry beast to emerge? Some people in town say the Jackalope can disembowel cattle with a single blow of his razor sharp horns. Others say the Jackalope is far more insidious, with supernatural powers, that he can lure grown men into a strange trance or make them go mad altogether. Onto the scene comes Richard Shope, a scientist at Rockefeller University. He heard rumors of the Jackalope on a hunting trip and offered a reward to any man who could capture one of the Jackalopes horns. Though many brave men tried, only one man could complete the task, and once in possession of the horn, Shope began his work. He ground up the horn with water and filtered it through porcelain so fine that certainly no bacteria or parasite could fit through, nothing with a brain or even a nucleus could pass through the porcelain. He rubbed the solution on the heads of healthy rabbits and guess what happened? They too grew hornsmany of them! Next, he injected the infected solution into the organs of healthy rabbits. They did not grow horns, instead many quickly died of aggressive cancers. The mystery of the Jackalope was solved. Does anyone have any idea what caused it? Viruses! But why did the infected cells cause harmless growths when applied to the surface of the skin and fatal cancers when injected? Well, we cant say for certain. What we do know is this: The balance between host and virus is a dance that has played out for millions of years, mostly peacefully. We all carry trillions of pieces of virus DNA that weve inherited from our parents and from our very distant ancestors. We also carry virus DNA weve come into contact with that our immune system has overcome. How many of you have had chickenpox? After you recovered, the virus remains latent in your cells and will likely be reactivated as you age and your immune system is weakened (example, stressful event.) If you were a bit younger, you may have had the option of having a chicken-pox vaccine. Then would you be at-risk for Shingles? Lying dormant? Latent in my cells? What does all of this mean? Okay lets look at this visually: someone sneezes 1. You inhale the virus particle, and it attaches to cells lining the sinuses in your nose 1. Every virus has adapted to attach to specific types of cellsskin, respiratory or digestive tracts, etc. 2. Virus releases its genetic instructions into the host cell. I like to think of a metaphor of a hijacker here. Suppose the healthy host cell is Santas workshop, and the Terminator ties Santa up, takes over the workshop and orders the elves to use their workshop materials to create more Terminators instead of toys. 3. Rapidly reproduces new viruses. 4. The new particles assemble the parts into new viruses. 5. Terminator continues to force the elves into making more Terminators until there are so many that they cannot fit in the building. Thats what happens when the virus particles become so many they burst the host cell, killing it, break free from the host cell and repeat. 6. New viruses spread into your bloodstream and also into your lungs. Because you have lost 10

cells lining your sinuses, fluid can flow into your nasal passages and give you a runny nose. By now, Santa has broken free and has called 911, 911 is like your immune system, and comes in to fight the Terminator viruses. 7. Viruses in the fluid that drips down your throat attack the cells lining your throat and give you a sore throat. Viruses in your bloodstream can attack muscle cells and cause you to have muscle aches, but eventually a healthy immune system will destroy the virus, and youre immune system will become stronger as a result. Heres the thing. Viruses arent really like me and you. Theyre incredibly sloppy, they only have an average of 8 genes we have 20,000so think of them as a baby trying to color in the lines or your Uncle Randy playing cards after one too many eggnogs. This how they rapidly mutate, and mess up genes. Some viruses have mutated to be like the undercover bad guys as opposed to the hijackers and do not reproduce right away. I think of them more like the sleeper cell, like a rogue elf whos lost the holiday spirit and is sabotaging the toys he makes. These viruses mix their genetic instructions into the host cell's genetic instructions. When the host cell reproduces, the viral genetic instructions get copied into the host cell's offspring. The host cells may undergo many rounds of reproduction, and then some environmental or predetermined genetic signal will stir the "sleeping" viral instructions into action (revisit chicken pox example). The viral genetic instructions will then take over the host's machinery and make new viruses as described above. In the Lytic Cycle (dont have to use the vocabulary terms if not necessary):

Viral DNA destroys Cell DNA, takes over cell functions and destroys the cell. The Virus replicates and produces copies of itself. There are symptoms of viral infection. Intensive viral infection takes place

In the Lysogenic Cycle:

Viral DNA merges with Cell DNA and does not destroy the cell. The Virus does not produce progeny. There are no symptoms of viral infection. Temperate viral replication takes place. So what might happen when a virus specifically targets the immune systems cells and is in this second phase? Would it eventually be present in all or nearly all of the immune cells? What if it then switched to the first phase, they are destroyed, now in a lowered immune system anything can take overbut well talk more about this in a few weeks. So who knows what can turn a man into a tree?

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