How to present a scientific paper

1. How to present a scientific paper Dr. Rebecca B. Riggins Department of Oncology, Georgetown University rbr7@georgetown.edu

2. Outline • Preliminary thoughts on the assigned reading • Typical structure of a scientific paper • Differences dictated by journal in which it is published • Discussion of Zhao et al., with comparisons to Schafer et al. • Final thoughts on the assigned reading

3. Today’s readings

4. ‘A scientific paper is like an hourglass’ Introduction (Materials and Methods) Results Discussion Abstract = mini hourglass

5. ‘The width of the hourglass is inversely proportional to importance’ • RESULTS and the HYPOTHESIS/RATIONALE are key when it comes to presenting a scientific paper • The Introduction is useful for background • The Discussion is a useful summary Introduction (Materials and Methods) Results Discussion

6. Zhao et al.: ErbB2, glycolysis, and breast cancer growth • Key words in the title will be better described in the • Introduction section • This should guide you in preparing 3 or 4 slides to • introduce the paper and why the study is important…

7. Cancer cell metabolism • Normal cells and cancer cells differ in how they derive energy from glucose • Normal: aerobic • Cancer: anaerobic • Cancer cell glycolysis dependence = Warburg effect • Explain this graphically using simple images O2+glucose glycolysis oxidative phosphorylation  38 ATP glucose glycolysis only  2 ATP

8. Please DON’T do this

9. A simple diagram of glycolysis vs. oxidative phosphorylation • Multiple molecules and • pathways can regulate • glycolysis • Some of these include: • Ras, PI3K, mTOR, Src • These are all targets of • the receptor tyrosine kinase ErbB2 Please cite your source! http://www.nutritionaloncology.org/images/aerobicGlycolysis.jpg

10. PI3K SHC ErbB1 ErbB1 ErbB1 ErbB1 ErbB2 ErbB2 Ras ErbB4 ErbB4 ErbB4 ErbB4 ErbB4 ErbB4 ErbB3 ErbB3 ErbB3 ErbB3 p38 PAK ERKs Raf PDK1 PKC JNK FKHR 2009 ProteinLounge.com GRB2 SOS Nck c-Jun c-Fos Elk1 TGFa Btc EGF Areg The full ErbB family signaling pathway Ereg Nrg1,2 HBEGF Nrg3,4 Anti-Apoptosis PLC-g Translation Akt/PKB CDC42 Gene Expression C mTOR GSK3b MKK3/6 MEK1/2 p70S6K

11. PI3K SHC Ras ErbB1 ErbB1 ErbB1 ErbB2 ErbB2 ErbB3 p38 PAK ERKs Raf PDK1 JNK FKHR 2009 ProteinLounge.com GRB2 SOS Elk1 c-Jun c-Fos TGFa Btc EGF Areg Relevant ErbB family signaling Ereg Nrg1,2 HBEGF Ligands Receptors Intracellular signaling Anti-Apoptosis Translation Akt/PKB Translation CDC42 Gene Expression C mTOR GSK3b MKK3/6 MEK1/2 p70S6K

12. How might ErbB2 regulate glycolysis? • Lactate dehydrogenase A (LDH-A) is a key glycolytic enzyme, and its expression is increased in mouse mammary epithelial cells that overexpress a form of ErbB2 • Heat shock factor 1 (HSF1) is a transcription factor that regulates glucose metabolism which is itself regulated by Ras (a target of ErbB2) • Does ErbB2 regulate glycolysis through these molecules?

13. Experimental results • Select key figures that illustrate the important points • These are often positive, but if there is room for criticism please provide it • Do NOT attempt to describe every panel of every figure

14. Overexpression of Erb2 promotes glycolysis in breast cancer cells O2 consumption http://www.nutritionaloncology.org/images/aerobicGlycolysis.jpg

15. Overexpression of ErbB2 increases LDH-A and HSF1 …and knockdown of ErbB2 reduces LDH-A expression and glycolysis

16. Downregulation of HSF1 = reduced LDH-A and glycolysis • Use of Hsf1 -/- cells is a way • to confirm siRNA results

17. Glycolysis inhibitors, ErbB2, and cancer 2DG = glucose analog that cannot undergo glycolysis Oligomycin = inhibitor of oxidative phosphorylation Oxamate = inhibitor of LDH, which converts pyruvate to lactate • Are ErbB2 overexpressing cells more sensitive to glycolysis inhibitors (and less sensitive to oxidative phosphorylation inhibitor)? http://www.nutritionaloncology.org/images/aerobicGlycolysis.jpg

18. Overexpression of ErbB2 = sensitivity to glycolysis inhibitors, and sensitivity to oxidative phosphorylation inhibitors Glycolysis inhibitor Oxidative phosphorylation inhibitor Similar results with 2DG in another cell line overexpressing ErbB2

19. Downregulation HSF1 inhibits ErbB2 effects on glycolysis and sensitivity to inhibitors • Again, use of Hsf1 -/- cells is a way • to confirm siRNA results

20. ErbB1 ErbB1 ErbB1 ErbB2 ErbB2 ErbB2 Summary of Results ErBB2 siRNA Upregulation of HSF1 protein HSF1 siRNA Increased LDH-A expression, enzyme activity Increased glycolysis Glycolysis inhibitors Increased cell growth

21. Discussion section • This is a summary of the major findings, and their importance for the field of study • The first paragraph is the summary • Subsequent paragraphs elaborate on the key findings and place them in context

22. Schafer et al.: metabolic defects due to cellular detachment • Nature papers are ‘different’

23. Thank you for your attention! • Questions? • If you would like an electronic copy of this presentation, you can download it here: http://openwetware.org/wiki/Riggins_Lab • Under Resources, click ‘Lectures’ • Click ‘How to present a scientific paper’