Simulation of Biological Systems

Simulation of Biological Systems
using Real-Time Object-Oriented Modeling

Introduction

• Why I am trying to model biological systems
• Professional interest in highly complex systems
• Possible analogies with complex telecommunication systems
• The purpose of this presentation is to exchange information
• I will do a 30 minute presentation
• Followed by 30 minute discussion, and questions in both directions

ObjecTime

• ObjecTime Developer is a tool for visually modeling, programming and executing real-time event-driven systems.
• I’ve recently been using it as a tool to produce a prototype simulation of some aspects of a cell and the nervous system.

Overview of My Prototype Model

• Major things that my prototype partially models:
• Enzyme reactions, especially Glycolysis and TCA pathways
• Neuron circuits, including action potentials, post synaptic potential, membrane proteins, dendrites, cell body, axons, etc.
• O₂/CO₂ cycle, including circulatory system, plants, atmosphere
• Amino acid structure of proteins
• Size:
• 100,000+ objects at run-time including 300 neurons
• 300 actor classes (enzymes, proteins, various containers & spaces)
• 100 C++ data classes (small molecules)

Some Modeling Issues

• What are the active objects - enzymes, other proteins, ribosomes, lipid bilayers, others?
• What are some other the architecturally significant entities and patterns?
• What does the cell control architecture look like?
• How to model trillions of components?
• How to model communication within and between cells?
• Wrestling with the modeling of emergent levels?

Active Objects

• What is an active object?
• Enzymes within cytoplasm and other cellular spaces
• Membrane proteins
• Are lipid bilayers active objects?
• Ribosomes
• What other active objects are there?

Architecturally Significant Entities 1

• Hierarchically-organized containment structures
• Cell, NervousSystem, Membrane, Organelles, etc.

Architecturally Significant Entities 2

• Spaces and space passageways
• Ex: protein and vesicle traffic outward from the nucleus

Cell Control Architecture

• Telecommunication devices such as telephone and data switches are built with two architectures:

• Example from a real telecommunication switch
• Analogies with biological cells

Modeling Trillions of Components

• Small molecules as C++ classes with internal counters
• Allows up to 4 billion instances of glucose, oxygen, etc. within each cellular space
• I assume that each small molecule is identical, and has the same state, as every other small molecule of the same type
• Enzymes and other active object instances represent all objects of that type within a given cellular space, using a counter
• I also assume that active objects of the same type are all identical
• Cells, Organelles
• Mitochondria are modeled as replicated actors
• Each can have its own individual state

Modeling Cell Communication

• Circulatory System example

Emergence

• Emergence of enzyme/protein behavior from amino acid polymer structures
• Emergence of metabolic pathways from enzyme/protein collective behaviors
• Emergence of neural circuit behavior from collections of neurons and synapses

What’s Next

• Attach Java applets to observe the running model
• simulated microscope views
• simulated laboratory graphs of substrate levels
• other views?
• Capture statistics in a database
• Continue developing Nervous System/Cell model
• Add missing details

Some of My Many Questions

• Am I building a reasonable extendible architecture?
• Have I chosen the right active objects?
• What significant architectural entities am I not aware of?
• What would be some interesting things to model from a biologist’s perspective?
• Is there any potential value of this type of modeling to the biological community? Educational? Research?
• Are Neurons and Erythrocytes representative of the range of cell types? What would be several other good cell types to test the model against?
• How many types of neurons are there? How divergent are they?
• Where can I find the kinetic constants (V_max, K_m) for major enzymes?
• Are the mechanoreceptors in the skin part of the neuron, or are they separate cells?
• What are the discrete compartments of the brain?
• What mechanism guarantees that connected neurons have compatible neurotransmitters?