Computational Biology

Question 1

What are the 2 types of models in genetic circuits?

Answer 1

Deterministic
– When the system consist many molecules
- Assumed mass action kinetics
- Ordinary Differential Equations

Stochastic
- When the number of molecules is small
- Gillespie algorithm

Question 2

What is a Model?

Answer 2

• A representation of the essential aspects of an existing system or of a system to be constructed which presents knowledge of that system in a usable form for its analysis or for its design.
• Models are simplified descriptions of reality.
• Models are built based on the type of questions that one seeks to answer:
  – How can one design a gene regulation system that produces proteins whose intracellular concentrations oscillate over time?

Question 3

Usefulness of modelling in
synthetic biology

Answer 3

To direct design
- Allows various designs to first be tested and optimized in silico using model-based computer simulations and mathematical analysis methods
before building the actual circuits.

Question 4

Why is Mathematical Modelling Important and useful?

Answer 4

• To facilitate efficient design of complex systems through the use of a rigorous Forward Engineering approach
• Rooted in mathematical modelling, model analysis and systems design and control.

Question 5

What’s Ordinary Differential
Equations

Answer 5

A mathematical expression of the function of an independent variable (such as time) and its derivatives (for example, concentrations of mRNA or protein)

Question 6

Ordinary Differential Equation Assumptions

Answer 6

1. Conservation of mass:
   * The principle that all mass in a closed system must remain constant over time.
2. Mass action kinetics:
   * A condition in which the rate of a given chemical reaction is proportional to the product of its reactant concentrations.

Question 7

Inducible Promoter Production Rate Equation

Answer 7

Basal Expression - Vmax[pdt]/(dissociation constant or Km + [pdt])

• when [pdt] = 0, hill = 0
• when [pdt]&raquo_space; Km, hill = Km
• when [pdt] = Km, hill = 0.5Vm

Question 8

steady state equations

Answer 8

[mRNA] = ktranscription/ymRNA

[pdt] = (ktranslation)(ktranscription)/(yprotein)(ymRNA)
= ktranslation(mRNA)/yprotein

Question 9

How to maximise the effectiveness of the model?

Answer 9

Which parameters have the ‘largest impact’ on the model behavior?
- Perform Sensitivity Analysis
* To determine sensitive parameters which are primarily responsible for significant changes in dynamical behavior.
* Study the changes in the model output or performance function with respect to small perturbations in individual specified parameter values.