Biophysics 101 Genomics and Computational Biology

2/15/01


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Table of Contents

Biophysics 101 Genomics and Computational Biology

Pro3: Last week's take home lessons

Networks Why model?

Net1: Today's story & goals Bio101 21-Nov-2000

Cell Division Cycle G2 arrest to M arrest switch

Hill coefficients

“The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes.”

Net1: Today's story & goals Bio101 21-Nov-2000

Stochastic kinetic analysis of developmental pathway bifurcation in phage lambda-infected E. coli cells.

Efficient exact stochastic simulation of chemical systems with many species& many channels

Utilizing Noise

Engineering stability in gene networks by autoregulation

Feedback simulation with linear stability analysis

Net1: Today's story & goals Bio101 21-Nov-2000

Copy Number Control Models

ColE1 CNC

Replication Transcription read-through

Assumptions?

Dynamic Mass Balance: ColE1 RNAI [concentration]

PPT Slide

Restate dynamic mass balance, solve for N(t)

Mathematica ODE program

Stochastic models for CNC

PPT Slide

Approach to studying behavior of defined genotypes …

Factors Constraining Metabolic Function

Description of metabolism

Net1: Today's story & goals Bio101 21-Nov-2000

Dynamic Description

Dynamic Description

Flux-Balance Analysis

PPT Slide

Stoichiometric Matrix

Additional Constraints

Flux Balance Example

FBA Example

FBA

Incomplete Set of Metabolic Constraints

Incomplete Set of Metabolic Constraints

Under-Determined System

FBA - Linear Program

Very simple LP solution

Applicability of LP & FBA

Precursors to cell growth

Net1: Today's story & goals Bio101 21-Nov-2000

in silico cells

H. pylori

E. coli in silico mutant growth

E. coli knockout mutants

Types of interaction models

ATP & Redox loads

Phase plane diagrams: concentration of metabolite A vs B over a specific time course

Phase plane diagrams: relating concentrations (ODE) or fluxes (FBA)

Acetate-Oxygen Phenotype Phase Plane

Acetate Experimental Data

Acetate 3-D Phase Plane

E. coli predicted mutant growth

Net1: Today's story & goals Bio101 21-Nov-2000

Author: George Church

Home Page: arep.med.harvard.edu