Be a LifeSaver: Detection is the Key to a Cure By Lynne Coté Mountain View High School (MUSD) 10th-11th graders, Biomedical Fundamentals In partial fulfillment of the requirements for TTE596c Summer 2012 SCENARIO When you here the word “Cancer” what feelings do you experience? The thought of you or someone you know having cancer can be devastating. According to the American Cancer Society, half of all men and one-third of all women in the US will develop cancer during their lifetimes. This means the likelihood of one of the 100 plus forms cancer directly or indirectly affecting your life is very high. Knowledge could be the key to survival. In normal cells damage to DNA is either repaired or the cell dies. In cancerous cells this regulation does not occur and the cell continues to divide uncontrollably. Normal cells are polite and will stop multiplying when they touch another cell. Cancer cells are rude and will continue dividing to form tumors. Sometimes the cancer cells migrate (metastasize) to other areas of the body and forms new tumors comprised of cloned cells from the original cancer cell. Today, millions of people are living with cancer or have had cancer. The risk of developing many types of cancer can be reduced by changes in a person’s lifestyle, for example, by staying away from tobacco, limiting time in the sun, being physically active, and healthy eating. There are also screening tests that can be done for some types of cancers so they can be found as early as possible – while they are small and before they have spread. In general, the earlier a cancer is found and treated, the better the chances are for living for many years. But is the same treatment the best for everyone? You are a scientist that works in the Research and Development department at a well-known biotechnology business known for developing diagnostic tools for various cancers. A person you love has been diagnosed with cancer and comes to you for advice on what type of treatment they should undergo. You are charged with developing a diagnostic tool (probes and antibodies) to determine the characteristics of your relative’s cancer so that you can suggest what the best treatments they should consider. Images? Stage 1 – Desired Results Established Goals Transfer Student will be able to (SWBAT) use bioinformatics resources Arizona Bioscience CTE (HUGO, NCBI, UCSC) to design probes and antibodies to enable Standards & MC: a diagnosis and recommendation of a possible treatment of a 10.0 Demonstrate patient. understanding and knowledge Student will be able to analyze cells using a microscope to of cell biology techniques evaluate characteristics involving presence of gene, mRNA and 10.1 Isolate and characterize cell protein production. lines 10.4 Use microscopes 10.5 Perform cytological tests, Meaning i.e. sectioning and staining Understandings Essential Questions 14.0 Demonstrate use of Bioinformatics involves using How do structures of biologically bioinformatics resources online databases and tools to important molecules (i.e. nucleic 14.1 Identify databases for analyze nucleotide sequences, acids-DNA & RNA, proteins) sequence analysis (NCBI) account for their function? RNA, and proteins. 14.2 Utilize electronic Nucleotide sequences code for databases/websites (NCBI) mRNA and protein. 14.3 Identify unknown sequences Probes can be designed to 14.4 Recognize relationships target (recognize) specific between sequences nucleotide sequences and 15.0 Demonstrate RNA. understanding and knowledge Probes and antibodies are of nucleic acid techniques used as diagnostic tools for 15.1 Detect specific nucleic acid specific cancers. sequences Probes and antibodies used in 15.8 Use sequence database identifying nucleotide sequences are fluorescently Arizona High School Life labeled to visually be seen Science Standards: through a microscope. S4C2PO1 Analyze the relationships among nucleic acids (DNA, RNA), genes, and Acquisition chromosomes S4C2PO2 Describe the molecular basis of heredity, in viruses and living things, including DNA replication and protein synthesis Student will know that unique nucleotide sequences of ~100 bp are needed to design a probe. Student will know that nucleotide sequences and mRNA are recognized by probes and proteins by antibodies. Student will know “Molecular Biology Central Dogma” (DNARNAProtein) and variations that occur. Student will know how cell’s communicate. Student will use the appropriate bioinformatics resource (HUGO, NCBI, UCSC) to accomplish a certain task. Students will analyze slides and distinguish between cancerous and noncancerous cells based on qualitative microscopic observations (# of gene copies, overexpressed RNA, excess protein production). Stage 2 - Assessments Performance Task (in GRASPS format) Goal: Your challenge is to develop diagnostic probes and antibodies to help a relative and their doctor determine the specific form of cancer they have and what treatment they should be undergoing. Role: You are a scientist in the Research and Development lab of a major biotechnology company. Audience: Your need to inform your relative and their doctor as to the genetic and molecular basis of the cancer. Situation: The challenge involves using bioinformatics to design diagnostic tools in the form of probes and antibodies. Product, Performance, and Purpose: You will develop probes and antibodies specific to the DNA, mRNA, and proteins that are being over expressed by you relative due to their cancer. Standards and Criteria for Success: Your product must meet the following standards: o Use HUGO to determine the official name of the gene of interest o Use a genome browser, NCBI or UCSC, to determine the gene sequence o Determine a probe specific to the gene of interest and produce a FASTA result sheet verifying that the probe sequence is unique only to the gene of interest o Research and determine a possible protocol of treatment best suited for your relative. Other Evidence: (quizzes, tests, prompts, work samples, labs, etc.) Labs: o Using HUGO to Find Official Gene Name o Using NCBI or UCSC to Isolate the Gene o Designing a Probe for Detection of the Gene Prompts: o Why, other than determining if a gene is present, is gene detection so important in determining a form of treatment for patients? o Why is it important to determine the official name (acronym) of a gene? o Which gene browser did you prefer? Why? o What are the important aspects to keep in mind when designing a probe? How can you increase probe specificity? Student Self-Assessment and Reflection Entries in Lab Books Reflections in Journals Peer Evaluations of Probes UNIT MAP Stage 3 – Learning Plan 1. Begin with the scenario and pose the question, “What would you do to save a loved one?” to hook the students into the importance of research. H 2. Introduce the students to the Essential Question and discuss the unit performance tasks and rubric. W 3. Ask students brainstorm three questions: (1) What are the key concepts of the Central Dogma of Molecular Biology and how do they interact with each other? (2) What is Cancer? (3) What is Bioinformatics? Their responses will act as a pre-assessment of prior knowledge and potential misconceptions. R, E2 4. Students view, “What is Cancer?”, video and select one of the suggested cancer readings to review. Students complete a journal entry summarizing video and reading they selected. In the entry they should include what they learned and what questions they still have about cancer. E 5. Class discusses results of previous brainstorming activity and reflects on revisions that should be made to clear up any misconceptions. Teacher addresses misconceptions not resolved by students’ reflection. E, R, E2 6. Students think of someone they actually knew that has or had cancer. The then complete the HUGO online activity for example gene (HER2) and for the gene they researched to get the official name and acronym. Students can follow written instructions or open video and follow along as they are working through the process. E, T 7. Next students will complete the Finding a Sequence Using NCBI or UCSC for their gene of interest. Students can follow written instructions or open video and follow along as they are working through the process. E, T 8. Students perform a BLAST or BLAT with the FASTA form created for their gene. E 9. Students analyze genes and determine the best probes based on BLAST/BLAT following written instructions. E 10. Students peer-review another student’s work on Steps 7-9 and discuss areas of improvement if needed. E2 11. Students repeat steps 7-10 for RNA. E 12. Students reflect back on DNA and RNA sequences and write relationships between the two in their journals. E, R 13. Students show printout of and explain their findings to the teacher. (Note: Teacher collects and reviews students’ results of HUGO, Finding a Sequence Using NCBI or UCSC, BLAST/BLAT, and probe design. Based on student’s explanation, teacher clears up misunderstandings or gaps on a student-by-student basis. E2 14. Students analyze teacher-prepared slides of HER2+ cancer slides for DNA and RNA and write in their journal how the two Pre-Assessments What pre-assessments will you use to check student’s prior knowledge, skill levels, and potential misconceptions? Prompt: What are the key concepts of the Central Dogma of Molecular Biology? Prompt: What is Cancer? Prompt: What is Bioinformatics? Progress Monitoring How will you monitor students’ progress toward acquisition, meaning, and transfer, during lesson events? Student progress will be monitored through: Verbal questioning of students throughout activities. Products of bioinformatics labs Analysis of tissue slides. slides compare and what that tells about the relationship between DNA and RNA. (Teacher checks journal entries and determines basis of class discussion to follow.) E, R, E2 15. Class discussion of alterations to Central Dogma that was presented in a simplified form in previous year. R 16. Students are asked to reflect and answer the question, If a treatment is found of a type of cancer, should everyone with that cancer get that treatment? Why or Why not? Student writes reflection in their journal. E, R 17. Class discussion of why personalized medicine comes into play in this case and why knowledge is power. E What are potential rough spots and student misunderstandings? Common genetics misunderstandings include the following ideas: Every aspect of the biology of an organism can be predicted from its genes. o It is much more complicated involving expression of genes and regulatory pathways. The relationship between genes and proteins as one-gene codes for one protein. o In actuality, one gene can code for more than one protein. Genes are uninterrupted sections of DNA that only code for a single protein. o This negates the understanding of introns and exons. The sole function of genes is to code for proteins, with the non-coding remainder being "junk DNA. " o However, it now appears that, although protein-coding DNA makes up barely 2% of the human genome, about 80% of the bases in the genome may be being expressed, so the term "junk DNA" may be a misnomer. The Central Dogma (DNA→ RNA→ Protein) no longer is the rule. o Genes → Gene expression → Proteins → Metabolic pathways → Sub-cellular structures → Cells → Tissues → Organs → Organisms o Epigenetics also comes into play. How will students get the feedback they need? Verbal Feedback (From Teacher & Peers) Written Feedback on Assessed Labs Activities • Are all three types of goals (acquisition, meaning, and transfer) addressed in the learning plan? Yes • Does the learning plan reflect principles of learning and best practices? Yes • Is there tight alignment with Stages 1 and 2? Yes • Is the plan likely to be engaging and effective for all students? I hope so. APPENDICES 3D Medical Animation-What is Cancer? Hallmarks of Cancer Hallmarks of Cancer: The Next Generation Roots of Cancer Understanding Cancer Video HUGO Instructions HUGO Instructional Video Finding a Sequence Using NCBI & UCSC Instructions Finding a Sequence Using NCBI & UCSC Video DNA Probe Design Instructions Bioinformatics Mindmap Unit Rubric