Our part in this project is the building of a computer model of a chromosome that allows for investigating the competing processes of transcription and replication. This is in close collaboration with the experimental work of Dr. Aladjem's group, who have done extensive sequencing to map the distribution of the transcription and replication initiation sites, and measured the relative kinetics of the competing processes. In addition to the spatial distribution of sites, our Monte-Carlo-based mathematical model takes into account the effects that the Cell's regulatory pathways have on the activities of the specific, DNA-binding, transcribing and replicating protein complexes. The Model thus allows for investigating the kinetic effects of changes in the spatial, temporal and regulatory-protein parameters of the system, which will be correlated with experiment. This project has been extended to model the dynamic development of cell colonies, to explore which factors in cell replication dominate in the formation of normal vs. tumor morphology.
