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From Membrane to Nucleus: Teaching Cell Signaling via the Ras Pathway.

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Presentation on theme: "From Membrane to Nucleus: Teaching Cell Signaling via the Ras Pathway."— Presentation transcript:

1 From Membrane to Nucleus: Teaching Cell Signaling via the Ras Pathway

2 C ELL B IOLOGY T EAM Kathleen Marrs, IUPUI James Marrs, IUPUI Mariah Judd, IUPUI Todd Murphy, Ivy Tech Community College (IUPUI) Robert Steven, University of Toledo Tomer Avidor-Reiss, University of Toledo Henry Chang, Purdue University Facilitators: Brian Kinkle, University of Cincinnati Sadie Hebert, University of Minnesota

3 C ONTEXT 0 This unit was prepared for a sophomore level cell biology course, taught mid way through the semester 0 This unit was designed with the flexibility to be scaled down to a freshman level biology course. 0 Unit designed to take 1-2 (one hour) class sessions

4 E XPECTED B ACKGROUND 0 Basics of cell structure and organelles 0 Protein control by phosphorylation 0 Understand that cells have the ability to respond to extracellular stimuli 0 Basics of cell signaling cascades (including various types of G-proteins)

5 T EACHABLE U NIT G OALS AND O UTCOMES I.Know specific components and relationship between components of the Ras pathway affecting cell proliferation. a)Order the sequence of proteins involved in the Ras pathway and describe their cellular location (BT 1-2) b)Describe the role of each component of the Ras pathway (BT 2-3) II.Evaluate the consequences of perturbations to the signaling pathway using real data. a)Analyze the effect of mutations on the components of the Ras pathway (BT 5-6) b)Practice the skill of analyzing data, controls and outcomes of experiments. (BT 4-5)

6 T EACHABLE U NIT G OALS AND O UTCOMES I.Know specific components and relationship between components of the Ras pathway affecting cell proliferation. a)Create a schematic depicting the RTK/RAS/MAP kinase signaling pathway in both the active and inactive states. (BT 1-2) b)Discuss the role and significance of each component of the Ras pathway. (BT 2-3) II.Evaluate the consequences of perturbations to the signaling pathway using real data. a)Analyze the effect of perturbation(s) on the components of the Ras pathway. (BT 4-5) b)Develop the skill of analyzing data, controls and outcomes of experiments. (BT 4-5) (BT=Bloom’s Taxonomy)

7 P RE -A SSIGNMENTS 0 Read the introduction from “The History of Ras: the Saga Continues” by Cox and Der, 2010 0 Review chapter section in text book that covers Ras pathway and review section questions 0 MAPK pathway video by Genentech (Youtube video) with video reflections

8 P RE -A SSIGNMENTS 0 Read the introduction from “The History of Ras: the Saga Continues” by Cox and Der, 2010 0 Review chapter section in text book that covers Ras pathway and review section questions 0 MAPK pathway video by Genentech (Youtube video) with video reflections

9 P RE -A SSIGNMENTS S UMMARY Modulation of signalling by Sprouty: a developing story Hong Joo Kim & Dafna Bar-Sagi Nature Reviews Molecular Cell Biology 5, 441-450 (June 2004) doi:10.1038/nrm1400

10 From Membrane to Nucleus: Teaching Cell Signaling via the Ras Pathway Our Tidbit

11 Activation of a G-protein involves ___________. a) Cleavage of the G-protein b) Methylation of the G-protein c) Binding of GTP d) Binding of GDP e) Techno music

12 Ras is a __________. a) Signal transduction molecule b) Transcription factor c) Calcium channel d) Membrane receptor e) Flavor of the Month at Starbucks

13 W HY D O W E C ARE A BOUT R AS ? 0 Ras is the most common oncogene in human cancer. 0 90% of all pancreatic cancers 0 25% of all human tumors 0 The Ras pathway provides a focus on the origins of cancer at the molecular level. 0 Ras is a key cellular protein for cell growth, differentiation and survival. http://www.sciencephoto.com/

14 R AS - ZLE D AZZLE P UZZLE Materials needed: 0 One 8.5x11 puzzle board 0 2 Envelopes labeled #1 “OFF” and #2 “ON” filled with puzzle pieces Working with your pod… 0 First: read and open envelope #1 “OFF” and assemble the pieces in the appropriate place on the puzzle board. (5 minutes) 0 Second: share your puzzle with the other pods at your table to compare and discuss. (5 minutes) Ras pathway modeling activity

15 R AS - ZLE D AZZLE P UZZLE “OFF” State

16 R AS - ZLE D AZZLE P UZZLE Working with your pod… 0 Third: read and open envelope #2 “ON” and add the new pieces to the puzzle board. (5 minutes) 0 Fourth: share your completed puzzle with the other pods at your table to compare and discuss. (5 minutes) Ras pathway modeling activity

17 R AS - ZLE D AZZLE P UZZLE “ON” State

18 What initially triggers a change in gene expression (in a WT cell)? a) Ras Activation b) GTP Hydrolysis c) MAP Kinase Phosphorylation d) Growth Factor – Receptor binding

19 R AS - ZLE D AZZLE P UZZLE : W HAT IS THE S IGNIFICANCE ? 0 What is the significance and outcome of… 0 the receptor – ligand interaction 0 the Ras activation 0 the MAP kinase cascade 0 What is the significance of the ERK translocation and what is one possible outcome?

20 W HEN G OOD C ELLS G O B AD : D ISRUPTIONS IN THE PATHWAY 0 What happens when we perturb the pathway? Summative Assessment

21 S UMMATIVE HOMEWORK 0 Practice with data analysis, controls and outcomes. 0 Uses real data from primary literature. Summative Assessment

22 R ITA L EVI -M ONTALCINI “Above all, don’t fear difficult moments. The best comes from them.” In Praise of Imperfection, Levi-Montalcini’s biography 0 Nobel laureate 0 Discovered growth factor signaling 0 Italian Jewish scientist 0 Lived to age 103 Image

23 T IDBIT G OALS AND O UTCOMES Know specific components and relationship between components of the Ras pathway affecting cell Create a schematic depicting the RTK/RAS/MAP kinase signaling pathway in both the active and inactive states.(BT 1-2) Discuss the role and significance of each component of the Ras pathway(BT 2-3) Goal I Outcome a) Outcome b)

24 With thanks to HHMI, The University of Minnesota and the : With thanks to HHMI, The University of Minnesota and the National Academies NorthStar (Midwest) Summer Institute (NANSI): Thanks also to Brian and Sadie, our amazing facilitators


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