Modeling Folate, One-carbon Metabolism and DNA Methylation

Grant Number:    
Funding Agency: NIH, NCI-R01-CA105437-01
PI: Michael C Reed and Fred Nijhout (Biology) are Co-PIs PI is Cornelia Ulrich of the Fred Hutchinson Cancer Research Institute. The figure $449,000 is the amount of the subcontract to Duke (over four years).
Effective Dates: 2005/01-2009/01
Amount: $449,000

Description: Here is the overall point of this project. There are 50 years of epidemiological data that provide correlations between different dietary factors and the incidence of various cancers. Typically the correlations are weak (and sometimes controversial). There are 10 years of data provide correlations between different gene tyoes and the incidence of various cancers. There are also many proposed mechanisms (again mostly unproven) through which cells might make the transition from normal to a cancerous state. The dietary inputs and the genetic inputs influence these proposed cancer mechanisms though the biochemistry of the cells. The purpose of project in the long term is make a mathematical model that makes explicit and quantitative the effects on cellular biochemistry of dietary changes and gene polymorphisms. A great deal is known about the individual reaction steps. What is not known is how the whole thing (the folate cycle, the methionine cycle, DNA methylations) works together. That is the goal of the mathematical modelling: to gain insight into the emergent properties of the whole system. I note that homocysteine is remethylated to methionine in the methionine cycle. Since homocysteine is a major risk factor for cardio-vascular diseases, understanding the folate and methionine cycles may suggest new treatment strategies for these disease too..