1. Group 1 Biology/Chemistry Interface “The Case of the Calcium Conundrum” Indiana University David Kehoe Joseph Pomerening University of Delaware Jennifer Nauen Patricia Walsh Meredith Wesolowski University of Massachusetts, Amherst J. Zane Barlow Coleman David Gross Facilitators: Justin Donato & Alison Hill 1

2. Context First semester, interdisciplinary chemistry- biology class for life science majors Large lecture format (> 70 students) The unit is designed to span four 75-min lectures

3. Teachable Unit Goal The goal of this teachable unit is for students to understand that inorganic chemistry plays a critical role in cellular function, using calcium as a model.

4. 1. the atomic structure of calcium and how this affects solubility. 1a. compare orbital structures of common metals; 1b. describe the aqueous solubilities of calcium compounds; 1c. predict the solubility of different mixtures of ionic compounds. 2. the mechanisms by which cells manage calcium insolubility and concentrations. 2a. summarize extracellular and subcellular calcium concentrations; 2b. explain how cells maintain their intracellular concentration gradient of calcium; 2c. describe why high levels of inorganic phosphate pose challenges to cells in their utilization of calcium. 3. the structure- function relationships between calcium and proteins. 3a. compare and contrast the tertiary structure of troponin and calmodulin with calcium bound and unbound, and relate it to their functions; 3b. describe why protein-protein interactions occur when calmodulin binds to calcium; 3c. predict the specific effects of particular point mutations in different domains of calmodulin. 4. higher order effects of calcium modulation on proteins in biological processes. 4a. relate plots of calcium kinetics to different physiological processes; 4b. understand the role of calcium binding proteins on higher-order biological processes; 4c. predict the effect of lack-of-function mutations in proteins that interact with calcium or calcium-binding proteins on the biological processes of objective 4b. Understand: Be able to: At the end of the unit, students should…

5. Learning Goals for Tidbit 1 Students will understand the difficulties that cells have with the inorganic chemistry of calcium and will propose potential mechanisms for regulation.

6. Learning Outcomes for Tidbit 1 1. describe the aqueous solubilities of calcium compounds 2. recognize why high levels of inorganic phosphate pose challenges to cells in their utilization of calcium 3. propose a range of possible mechanisms by which cells manage the potential toxicity of calcium Students will be able to:

7. Who is this guy? Дми́трий Ива́нович Менделе́ев Dmitri Ivanovich Mendeleev

8. Name the TOP 6 Elements (by mass) in Your Body

9. Solubility Rules

10. Which of these ion pairs will form an insoluble precipitate? C n+ +A m- CmAnCmAn insoluble a.Ca 2+ + PO 4 3- b.Na + + PO 4 3- c.K + + Cl - d.K + + PO 4 3- e.Ca 2+ + Cl - PO 4 3- (4 mM) Ca 2+ (0.1 µM) Na + (5 mM) Cl - (3 mM) K + (140 mM) Cell

11. Millions of calcium ions are permitted to enter the cell through channels in the plasma membrane. These calcium ions are related to important biological functions such as neuronal signaling. Could this be a problem? Why? If so, how might the cell be able to deal with the potential problem? Brainstorming

12. Learning Goal for Tidbit 2 Students will understand how proteins interact with inorganic ions and the biological significance of those interactions. The specific example for this tidbit is calmodulin.

13. Learning Outcomes for Tidbit 2 1. describe the structure of calmodulin in its open and closed forms 2. interpret data on the effect of mutating calmodulin kinase on brain function Students will be able to:

14. R. Franklin A. Einstein G. W. Carver S. Kakiuchi B. Barres

15. A. B. C. D. E. OK, who was the person in the middle? B. Barres R. Franklin G. W. Carver S. Kakiuchi A. Einstein

17. Calmodulin Think Pair Share What’s similar here? What’s different here? A B

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20. 20 Morris Water Maze 20 Target Quadrant (TQ)

21. 21 Which of the following best describes the data? A. WT mice have better overall memory than mutant mice B. Mutant mice have better overall memory than WT mice C. WT mice have better memory than mutant mice at certain times post training D. Mutant mice have better memory than WT mice at certain times post training E. At some times post training WT and mutant mice have the same memory

22. 22 Which of the following best describes the data? A. WT mice have better overall memory than mutant mice B. Mutant mice have better overall memory than WT mice C. WT mice have better memory than mutant mice at certain times post training D. Mutant mice have better memory than WT mice at certain times post training E. At some times post training WT and mutant mice have the same memory

23. 23 Which of the following best describes the data? A. WT mice have better overall memory than mutant mice B. Mutant mice have better overall memory than WT mice C. WT mice have better memory than mutant mice at certain times post training D. Mutant mice have better memory than WT mice at certain times post training E. At some times post training WT and mutant mice have the same memory

24. 24 Wild type CaM kinase mutant Ref: Frankland, O’Brien, Ohno, Kirkwood & Silva, CaMKII-dependent plasticity in the cortex is required for permanent memory, Nature 411, 309-313 (2001)

25. Summary 25