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’

• 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

Zhao et al.: ErbB2, glycolysis, and breast cancer growth

• Key words in the title will be better described in theIntroduction 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

• 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

Please DON’T do this

A simple diagram of glycolysis vs. oxidative phosphorylation

http://www.nutritionaloncology.org/images/aerobicGlycolysis.jpg

• Multiple molecules and pathways can regulateglycolysis• Some of these include:

• Ras, PI3K, mTOR, Src

•These are all targets ofthe receptor tyrosine kinase ErbB2

Please cite your source!

The full ErbB family signaling pathway

E

rbB

1

E

rbB

1

c-FosElk1 c-Jun

mTOR

PDK1

HBEGF

PLC-

PKC

Nck

Ras

Raf

MEK1/2

ERKs

p38

JNK

PI3K

p70S6K

Akt/PKB

PAK

CDC42

Anti-Apoptosis

E

rbB

1

E

rbB

2

Er

bB3

ErbB4

TGFEGFAreg

Btc

Ereg

Nrg1,2

MKK3/6

GR

B2

SOS

SHC

Nrg3,4

TranslationTranslation

Gene ExpressionGene Expression

Er

bB3

Er

bB3

GSK3

FKHR

ErbB4

ErbB4

ErbB4

ErbB4

E

rbB

1

ErbB4

ErbB3

E

rbB

2

2009ProteinLounge.com 2009ProteinLounge.com

C

Relevant ErbB family signaling

E

rbB

1

E

rbB

1

c-FosElk1

c-Jun

mTOR

PDK1

HBEGF

Ras

Raf

MEK1/2

ERKs

p38

JNK

PI3K

p70S6K

Akt/PKB

PAK

CDC42

Anti-Apoptosis

E

rbB

1

E

rbB

2

TGFEGFAreg

Btc

Ereg

Nrg1,2

MKK3/6

GR

B2

SOS

SHC

TranslationTranslation

Gene ExpressionGene Expression

GSK3

FKHR

ErbB3

E

rbB

2

2009ProteinLounge.com 2009ProteinLounge.com

C

Ligands

Receptors

Intracellularsignaling

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 wayto confirm siRNA results

Glycolysis inhibitors, ErbB2, and cancer

http://www.nutritionaloncology.org/images/aerobicGlycolysis.jpg

2DG = glucose analog that cannot undergo glycolysis

Oxamate = inhibitor of LDH, which converts pyruvate to lactate

Oligomycin = inhibitor of oxidative phosphorylation

• Are ErbB2 overexpressing cells more sensitive to glycolysis inhibitors (and less sensitive to oxidative phosphorylation inhibitor)?

Overexpression of ErbB2 = sensitivity to glycolysis inhibitors, and sensitivity to oxidative phosphorylation inhibitors

Glycolysis inhibitor Oxidative phosphorylation inhibitor

Similar results with 2DG in anothercell line overexpressing ErbB2

Downregulation HSF1 inhibits ErbB2 effects on glycolysis and sensitivity to inhibitors

Again, use of Hsf1 -/- cells is a wayto confirm siRNA results

Summary of Results

E

rbB

1

E

rbB

2

Upregulation of HSF1 protein

Increased LDH-A expression, enzyme activity

E

rbB

1

E

rbB

2

E

rbB

1

E

rbB

2

Increased glycolysis

Increased cell growth

Glycolysis inhibitors

ErBB2 siRNA

HSF1 siRNA

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’