User:Johnsy/Lipoprotein Modelling

Modelling Lipoprotein Metabolism

Figure 1 A Lipoprotein

BEng Final Year Individual Project 2007/2008

John Sy
Department of Bioengineering
Imperial College London

Supervisor: Dr. M Barahona
Co-Supervisor: Prof. K Parker

Abstract

The field of systems biology is an expanding field which seeks to help understand biological phenomena using the language of mathematics and engineering. With statistics showing that a larger population of the West is becoming clinically obese and the incidence of cardiovascular diseases dramatically increasing in the past decade, it is imperative that we take a step towards understanding the mechanism behind disease and how to correct it. This project aims to tackle the problem of hypercholesterolemia and extend current mathematical models of lipoprotein production, delivery, and metabolism. Furthermore, the project seeks to develop a mathematical understanding of how statins affect the de novo synthesis of cholesterol within both hepatic and extrahepatic cells.

Aims

Part 1: Background

• Understand the mechanism by which cholesterol is produced in cells (cholesterol biosynthesis) beginning from Acetyl-CoA and which enzymes limit the rate at which cholesterol and its derivatives are produced.
• Understand the pathways for maintaining cholesterol homeostasis in the human body and various diseased states resulting in a level of blood cholesterol away from homeostasis.
• Develop an understanding of the structure and function of lipoproteins and how they are transported into and out of the cells in the human body, especially the liver and intestinal cells.
• Reserach and understand current models of lipoprotein transport and metabolism.

Part 2: Model Extension & Development

• Adapt and develop the current models of lipoprotein metabolism to more accurately reflect the biochemistry of the process.
• Adapt and develop the current models to fit specific cell types, such as hepatocytes, and account for the variation in function of those different cell types.

Part 3: Model Testing & Limits

• Understand the mechanism by which statins affect HMG-CoA reductase and test input parameters of the mathematical models developed to account for its actions.
• Understand the importance of lipoproteins, especially LDL, to the generation of atherosclerosis.
• Test the model with various physiological parameters in an attempt to better understand the effects of diseases such as familial hypercholesterolemia (FH)

Project Sections

1. Cholesterol Biosynthesis
2. Cholesterol Homeostasis
3. Lipoprotein Structure & Function
4. Current Models of Lipoprotein Metabolism
5. Biochemical Modelling
6. Lipoprotein Model Development
7. References