Case of the Calcium Conundrum (PowerPoint) Madison 2010

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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
Context
• First semester, interdisciplinary chemistrybiology class for life science majors
• Large lecture format (> 70 students)
• The unit is designed to span four 75-min
lectures
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.
At the end of the unit, students should…
Understand:
Be able to:
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 structurefunction 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.
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.
Learning Outcomes for Tidbit 1
Students will be able to:
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
Who is this guy?
Дми́трийIvanovich
Ива́нович Менделе
́ ев
Dmitri
Mendeleev
Name the TOP 6 Elements
(by mass)
in Your Body
Solubility Rules
Which of these ion pairs will form an insoluble precipitate?
Cn++Am-
CmAn
Na+
Ca2+
insoluble
(5 mM)
(0.1 µM)
PO43-
Cl-
(3 mM)
a. Ca2++ PO43b. Na++ PO43-
+
K
(140 mM)
c. K++ Cld. K++ PO43e. Ca2++ Cl-
(4 mM)
Cell
Brainstorming
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?
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.
Learning Outcomes for Tidbit 2
Students will be able to:
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
B. Barres
S. Kakiuchi
A. Einstein
R. Franklin
G. W. Carver
OK, who was the person in the middle?
A.
B.
C.
D.
E.
B. Barres
R. Franklin
G. W. Carver
S. Kakiuchi
A. Einstein
Calmodulin
Think
Pair
Share
A
What’s similar here? What’s different here?
B
18
Target Quadrant (TQ)
Morris
Water Maze
20
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
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
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
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)
24
Summary
25
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