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Introduction Nancy Griffeth January 6, 2014 Funding for this workshop was provided by the program “Computational Modeling and Analysis of Complex Systems,” an NSF Expedition in Computing (Award Number 0926200).

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Introduction. Nancy Griffeth January 6, 2014. Funding for this workshop was provided by the program “Computational Modeling and Analysis of Complex Systems,” an NSF Expedition in Computing (Award Number 0926200). Outline. What will we be doing Why I think computational biology is fun. - PowerPoint PPT Presentation

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Page 1: Introduction

Introduction

Nancy Griffeth

January 6, 2014

Funding for this workshop was provided by the program “Computational Modeling and Analysis of Complex Systems,” an NSF Expedition in

Computing (Award Number 0926200).

Page 2: Introduction

Outline

What will we be doing

Why I think computational biology is fun

Page 3: Introduction

Subject Matter

How to model signaling pathways, such as those that control cell proliferation

Workshop Information

Page 4: Introduction

Schedule

This week: Introductory lectures Next week: Initial modeling problems Third week: Projects Last two days

Team presentations Final visiting lecture

Workshop Information>Schedule

Page 5: Introduction

Pedagogical Approach

Collaborative Questions are always welcome Discussion is encouraged! Scribe to record unanswered questions

Problem-oriented: three problems Frog cell cycle EGFR signaling pathway First passage time distributions

Workshop Information>Pedagogical Approach

Page 6: Introduction

Pedagogical Approach

Interdisciplinary team oriented At least 1 chemistry/biology expert At least 1 computer science expert At least 1 math expert

Workshop Information>Pedagogical Approach

Page 7: Introduction

Speaking of Interdisciplinary…Workshop Information>Pedagogical Approach

xkcd.com

http://xkcd.com/
Page 8: Introduction

General Learning Objectives

Be aware of some hypotheses about how cancers develop

Be able to model cellular signaling pathways

Learn to function on interdisciplinary teams

Investigate some research problems Meet new people and have some fun!

Workshop Information>Pedagogical Approach

Page 9: Introduction

Specific Learning Objectives

Learn how cells initiate cell division using signaling Investigate the mechanisms that initiate cell division

and ensure that cells are copied accurately Be able to model signaling pathways that initiate cell

division, using wiring diagrams and reaction rules Create computer-processable models of signaling

pathways Simulate their behavior Investigate their properties

Study distributions of first passage times, to support research on coarse-graining models

Workshop Information>Pedagogical Approach

Page 10: Introduction

Questions or Discussion?

Page 11: Introduction

What’s I like about computational/systems biology Biology matters! Computational techniques help us

understand biology Cells act a lot like computers

Cells make binary choices Cells have modular parts Different kinds of cells share the same

mechanisms

Page 12: Introduction

Computational techniques

Organize data Describe behaviors as a whole Bridge gaps where data is missing Suggest hypotheses

Page 13: Introduction

Amazing Mechanisms: Cell Cycle Regulation

Page 14: Introduction

Cell Cycle Regulation

Page 15: Introduction

Great movies:Protein Production

TranscriptionCentral dogma

Figure from wikipedia article on the central dogma

Transcription

Translation

http://www.youtube.com/watch?v=WsofH466lqk
http://www.dnalc.org/resources/3d/central-dogma.html
Page 16: Introduction

Feedback loops!!

Wiring diagrams

Negative autoregulation: a protein represses its own production

Provides a quick increase to a robust level

Page 17: Introduction

Digital Circuits!!

cAMP signals absence of glucose

cAMP activates X X binds to the DNA promoter,

but is not enough by itself to start arabinose metabolism

X promotes transcription of Y; arabinose activates Y

X and Y together binding to the DNA promoter results in production of the enzymes that metabolize arabinose

Figure from Alon, “An Introduction to Systems Biology”

Page 18: Introduction

Rube Goldberg Devices:Signaling Pathways

An external signal (molecule) arrives

Binds to a receptor Changes in the

receptor cause internal actions…

Which cause cascading actions

Page 19: Introduction

Regulating cell growth, proliferation, and differentiation

Page 20: Introduction

Cell as Information Processor

http://en.wikipedia.org/wiki/Cell_signaling

Page 21: Introduction

Garbage Collection: Protein degradation Ubiquitin

Tags proteins for destruction

Like garbage collection!!

Page 22: Introduction

Rulebender Tool

Page 23: Introduction

Research Problems

Curing cancer: How do signaling pathways relate to the development of cancer?

Computational complexity: how can we simplify the models enough to make them tractable?

Page 24: Introduction

Relationship to cancer

Mitosis signals stay in on position Cells learn to send growth signals to

themselves Cells send growth signals to other cells

inappropriately Cells send signals for creation of blood

vessels

Page 25: Introduction

Simplifying models

Computationally complex

Modular? Course-graining Need subsystems

with behavior we can characterize

Page 26: Introduction

What you will learn…

Regulation of the cell cycle A rule-based language to model cellular

processes High-level view of how models can be

“solved” Signaling pathways Ras pathway Bistability And more…


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