1. What is the Evolutionary History and Function of Exendin? Mary Ritke Sandra Davis Octavian Nicolio Angela McKinney-Williams

2. Previous Observations GLP-1 is a ligand for the GLP-1 receptor (Methuselah) that enhances glucose uptake in cells. Exendin is a protein found in the venom of the Heloderma suspectum, a.k.a. the Gila monster Trp Cage is a synthetic peptide with interesting thermodynamic properties, however Exendin has been found to have the Trp Cage motif. Compared to GLP-1, Exendin binds the GLP-1 receptor more tightly and is a more effective glucose uptake stimulator. What an interesting phenomenon!!!!

3. Heloderma suspectum

4. Our objectives are to: Design and test a learning module to help students determine how to use existing data (above) to understand the relationship between two seemingly unrelated proteins: a venom protein and a glucose metabolism effector. We (and our students will) –Formulate hypotheses –Plan experiments to further understand the evolutionary history and function of GLP-1-like proteins and Exendin. Use existing data bases to test two hypotheses regarding the evolution of GLP-1 and Exendin.

5. Two Hypotheses to be tested

7. Predicted Tree Under Hypothesis 1

8. Predicted Tree Under Hypothesis 2

9. We used BLAST to find the amino acid sequences of GLP-I related proteins in 13 different species –Heloderma suspectum (Gila monster) –Hoplobatrachus rugulosus (crowned bullfrog) –Petromyzon marinus (sea lamprey) –Agkistrodon piscivorus (cottonmouth) –Gallus gallus (chicken) –Mus musculus (mouse) –Neoceratodus forsteri (Australian lungfish) –Homo sapiens (human) –Rana catesbeiana (bullfrog) –Amphiuma tridactylum (three-toed salamander) –Pan troglodytes (chimpanzee) –Ictalurus punctatus (channel catfish) –Squalus acanthias (spiny dogfish)

11. “Molded results vary depending on child’s age and level of skill”