Problem being addressed and the importance for society:
Some people are genetically at risk for developing a specific disease. However, not everybody who is genetically at risk, will automatically develop the disease. One of the reasons for this is that in addition to genetic factors, environmental factors can influence whether a disease will develop. The aim of this project is to determine which genetic and environmental factors are involved in the development of complex diseases, and understand their downstream molecular mechanisms. Understanding how and why these diseases develop, will allow for the identification of high risk individuals in which preventive measurements can be taken to reduce their risk of developing specific diseases (e.g. prevent exposure to the identified environmental factors). Moreover, this knowledge may aid in the identification of new drug targets for these diseases.
The overall objectives of this project are:
1) Identify the downstream consequences of genetic variants that are associated with immune-mediated diseases.
2) Identify which environmental stimuli alter the downstream molecular effects of genetic variants that are associated with immune-mediated disease, through the generation of genotype and single-cell RNA-seq data on blood cells from ~120 individuals that have been stimulated with ~3 different pathogens.
3) Identify other environmental risk factors that influence downstream molecular effects of these genetic variants that are associated with immune-mediated disease, by re-analyzing genotype and RNA-seq data from >20,000 samples, generated in the presence and absence of many different (disease) stimuli, to identify those conditions (e.g. bacterial infections, detectable using the RNA-seq data itself).
