How asthma and depression impact upon cardiovascular disease: a study of co-morbidities. (360G-Wellcome-207224_Z_17_Z)

The supervising group has modelled the impact of the innate immune response on the cholesterol biosynthesis pathway in previous publications. Using microarray measurements as a crude estimate of protein concentrations, from a time course study of CMV infected macrophages, we incorporated time course enzyme concentrations into an ordinary differential equation (ODE) model of the pathway and used numerical integration to simulate the impact of enzyme concentration changes that result from infection on pathway activity. The group also has a novel model of atherosclerosis and has previously combined this with microarray data to investigate the impact of infection on plaque formation in atherosclerosis. Here, the student will extract measurements of transcriptional activity of the genes coding for proteins associated with atherosclerosis pathways from published studies of CD4+ T-cells from patient cohorts with asthma, depression, asthma with depression and a control cohort. These measurements will be used to estimate protein abundance and will be incorporated into our ODE model of atherosclerosis disease progression. The resulting model will be numerically integrated to simulate the inflammatory impact of asthma, depression and asthma with depression on atherosclerosis plaque formation in order to explore their role as comorbidities of cardiovascular disease.