The impact of comorbidities: Innate immune reprogramming of atherosclerosis in response to infection. (360G-Wellcome-202391_Z_16_Z)

In previous published studies, the supervising group modelled the impact of the innate immune response on the cholesterol biosynthesis pathway. This was achieved by taking microarray measurements of bone marrow derived macrophages (BMDM) at half hour intervals for 12 hours post infection by murine cytomegalovirus. By using these measurements of transcriptional activity as crude relative approximations to protein abundance, the group was able to construct a time course of enzyme concentrations and introduce this into an ordinary differential equation (ODE) model of the pathway, using numerical integration to simulate the impact of the changing enzyme concentrations on the flux through the pathway. In this project, the student will extract measurements of the transcriptional activity of the genes coding for the proteins associated with atherosclerosis pathways from the same microarray datasets. These measurements will be used as crude estimates of protein abundance and will be incorporated into ODE models of the atherosclerosis disease process that have already been produced by the supervisor’s group. The resulting model will be numerically integrated to simulate the impact of the changing proteins concentrations on atherosclerosis disease progression as an indicator of the impact of innate immune regulation.