How to present a scientific paper Dr. Rebecca B. Riggins Department of Oncology, Georgetown University rbr7@georgetown.edu 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 Today’s readings ‘A scientific paper is like an hourglass’ Introduction (Materials and Methods) Results Discussion Abstract = mini hourglass ‘The width of the hourglass is inversely proportional to importance’ Introduction (Materials and Methods) Results Discussion • RESULTS and the HYPOTHESIS/RATI ONALE are key when it comes to presenting a scientific paper • The Introduction is useful for background • The Discussion is a useful summary 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… Cancer cell metabolism • Normal cells and cancer cells differ in how they derive energy from glucose • Normal: aerobic O2+glucose glycolysis oxidative phosphorylation 38 ATP • Cancer: anaerobic glucose glycolysis only 2 ATP • Cancer cell glycolysis dependence = Warburg effect • Explain this graphically using simple images Please DON’T do this 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 http://www.nutritionaloncology.org/images/aerobicGlycolysis.jpg Please cite your source! The full ErbB family signaling pathway Ereg Nrg 1,2 Areg Nrg 3,4 SHC SOS PI3K Nck PDK1 Ras PLC-g Akt/ PKB FKHR CDC42 Raf PAK Anti-Apoptosis MKK 3/6 MEK 1/2 mTOR PKC GSK3b p70S6K JNK p38 ERKs Translation c-Fos El k1 C 2009 ProteinLounge.com c-Jun Gene Expression Relevant ErbB family signaling Ligands Ereg Nrg 1,2 Areg Receptors SHC PI3K SOS Intracellular signaling PDK1 Ras Akt/ PKB FKHR CDC42 Raf PAK mTOR Anti-Apoptosis MKK 3/6 MEK 1/2 GSK3b p70S6K JNK p38 ERKs Elk1 c-Fos c-Jun C 2009 ProteinLounge.com Gene Expression Translation Translation 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? 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 Overexpression of Erb2 promotes glycolysis in breast cancer cells O2 consumption http://www.nutritionaloncology.org/images/aerobicGlycolysis.jpg Overexpression of ErbB2 increases LDH-A and HSF1 …and knockdown of ErbB2 reduces LDH-A expression and glycolysis Downregulation of HSF1 = reduced LDH-A and glycolysis Use of Hsf1 -/- cells is a way to confirm siRNA results 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 Overexpression of ErbB2 = sensitivity to glycolysis inhibitors, and sensitivity to oxidative phosphorylation inhibitors Glycolysis inhibitor Similar results with 2DG in another cell line overexpressing ErbB2 Oxidative phosphorylation inhibitor Downregulation HSF1 inhibits ErbB2 effects on glycolysis and sensitivity to inhibitors Again, use of Hsf1 -/- cells is a way to confirm siRNA results Summary of Results ErBB2 siRNA Upregulation of HSF1 protein HSF1 siRNA Increased LDH-A expression, enzyme activity Increased glycolysis Increased cell growth Glycolysis inhibitors 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 Schafer et al.: metabolic defects due to cellular detachment • Nature papers are ‘different’ 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’
