User:Johnsy/Lipoprotein Modelling
Modelling Lipoprotein Metabolism
BEng Final Year Individual Project 2007/2008
John Sy
Department of Bioengineering
Imperial College London
Supervisor: Dr. M Barahona
Co-Supervisor: Prof. K Parker
Project Description
Theoretical analysis of a dynamical model of lipoprotein metabolism derived by combining a cascading process in the blood and cellular level regulatory dynamics. Lipoprotein metabolism is at the root of the regulation of lipid and cholesterol delivery in the body and related to the appearance of atherosclerosis. Our low-dimensional, nonlinear model exhibits bistability between a low and a high cholesterol state in the blood although the concentration of cholesterol in the cell remains robustly constant. The project will establish the connection between parameters in the problem and medical and genetic conditions, possibly through the analysis of experimental data from St Mary’s. It will also involve the extension of the current model to consider the effect of other regulatory routes in the body.
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)
