1. Group 6 GERMS, DRUGS and GENES: Revealing mechanisms of gene expression using antibiotics Alejandro Calderon-Urrea Nancy Connell Nigel Crawford Mamta Rawat Ella Tour Facilitator: Ken Burtis Level: Lower Division Biology Class for Majors

2. Learning Goals: 1.The student will be able to understand how genotype determines phenotype. 2.The student will identify steps in gene expression and how some drugs affect different levels of gene expression.

3. Learning Outcomes 1.The student will find and illustrate the mechanisms of action of certain antibiotics and relate these actions of antibiotics to steps in gene expression. 2.The student will be able to explain how resistance to antibiotics arises from a change in the genetic material of the cell. 3.The student will be able to apply mechanisms of resistance to antibiotics in bacteria to resistance to drugs in eukaryotic cells 4.The student will propose strategies for the development of new drugs.

4. Learning Outcomes 1.The student will find and explain the mechanisms of action of certain antibiotics and relate these actions of antibiotics to steps in gene expression. 2.The student will be able to explain how resistance to antibiotics arises from a change in the genetic material of the cell. 3.The student will be able to apply mechanisms of resistance to antibiotics in bacteria to resistance to drugs in eukaryotic cells 4.The student will propose strategies for the development of new drugs.

5. GENOTYPE PHENOTYPE ?

6. GENOTYPE PHENOTYPE (DEATH) Antibiotics

7. Group share (3 minutes) Assign each antibiotic to two members of the group. The members find out about the target of the antibiotic and report to group. 1. ciprofloxacin 2. rifampicin 3. tetracycline

8. Drawing exercise (3 minutes) Draw a bacterial cell on poster paper and illustrate the targets of antibiotics.

9. Antibiotics & their Modes of Action Vancomycin trimethoprim Tetracycline Rifampicin Ciprofloxacin Polymyxin B

10. Clicker question (2 min) How do antibiotics become ineffective against bacterial infection? A. Human body develops mechanisms to inactivate the antibiotic. B. Treating bacteria with antibiotics changes their physiology so they become resistant C. The antibiotic causes the mutation in the bacteria which leads to resistance D. Existing mutants in the bacterial population that are already resistant to the antibiotic are selected and proliferate E. All of the above In class: Peer instruction (Vote, Think pair share, Re-vote) followed by discussion of different options by instructor

11. Genotype 1 Phenotype 1: Susceptibility Phenotype 2: Resistance Genotype 2

12. http://www.niaid.nih.gov/topics/antimicrobialResistance/

14. Genotype 1 Phenotype 1: Susceptibility Phenotype 2: Resistance Genotype 2

15. We have learned that resistance arises in populations by mutation or acquisition of new genes. How could these genetic changes lead to antibiotic resistance? Specify potential processes, targets, and mechanisms. Group share.

16. Look up on the internet mechanisms for resistance of your antibiotic. Report to group. “Call out” three groups for each antibiotic.

17. Can you think of another instance where chemical resistance happens? Group share. Report out

18. Homework A patient is undergoing cancer treatment with an anti-cancer drug. For a while, the cancer is responding and the tumor is shrinking significantly. However, after 6 months, the cancer comes back: the tumor cells continue to proliferate even when the dosage of the drug is increased. A. Based on what you've learned today, suggest two possible mechanisms that allowed the cancer cells to become resistant to the drug. B. What would you propose as a new drug that would target this cancer? The answers will be discussed next class.

19. Pre-test/Post-test 1.Explain how genetic information is transferred from DNA to RNA to proteins. Include the terms: DNA replication, transcription, translation. (LOC) 2.What could be the consequences to this flow of information if a mistake occurs during DNA replication? (LOC/HOC) 3.Describe four examples of mechanisms of action of an antibiotic on a bacterial cell. (LOC) 4.Explain a mechanism of antibiotic resistance. Provide an example. (LOC) 5.Why aren’t antibiotics as effective in treating disease as they used to be? (HOC)

20. Summative assessment: 1.The student will find and illustrate the mechanisms of action of certain antibiotics and relate these actions of antibiotics to steps in gene expression. 2.The student will be able to explain how resistance to antibiotics arises from a change in the genetic material of the cell. 3.The student will be able to apply mechanisms of resistance to antibiotics in bacteria to resistance to drugs in eukaryotic cells. 4.The student will propose strategies for the development of new drugs.