Deciphering the genetic basis of human immune response variation

• Applicant: Dr. Sarah Kim-Hellmuth
• Subject Area: Human Genetics ; Immunology ; Medical Informatics and Medical Bioinformatics
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 459153572

The human immune system plays a key role in host protection against microbial infections, autoimmune and inflammatory diseases, cancer, metabolism, and ageing. Large genome-wide association studies have implicated hundreds of genetic loci in immune-related genes highlighting the immune system’s role in the biological mechanism underlying genetic risk to numerous diseases. However, for the vast majority of these genetic variants, we have little understanding of their functional effects and their context-specificity. This challenge is addressed by the proposed research. The overarching aim is to characterize the genetic basis of human immune response variation, which will advance our understanding of disease-associated variants and answer questions of genome function plasticity that is shaped by gene-by-environment interactions. For this purpose, we will first study the in vivo transcriptional immune response using long-read cDNA-sequencing in a cohort of 250 extensively characterized participants of a yellow fever vaccination study. Integrating the transcriptional data then with the rich genetic and molecular characterization available for this cohort provides a unique opportunity to build a multi-layer map of the genetic basis of immune response variation. This approach will develop a roadmap for complex traits at large and enable the move from genetic discovery to functional interpretation and ultimately clinical impact.

• DFG Programme: Independent Junior Research Groups