The Question
A first line of defense against pathogens, innate immunity is essential for life, providing an immediate but nonspecific response through physical barriers, immune cells and various proteins. It recognizes and responds to a broad range of microbial threats using pattern recognition receptors to detect conserved pathogen-associated molecular patterns.
This complex response demands precision. The activity of innate immune signaling must be properly regulated to orchestrate a transient and balanced response. Errors in controlling innate immunity can lead to disease: Inflammation caused by the aberrant activity of innate immune receptors is now being viewed as a major driver of several human diseases as well as natural aging. But the exact functioning of the innate immune response is still not fully understood.
“My inspiration to pursue basic research stems from a combination of curiosity, a passion for discovery, and the desire to contribute to the foundational understanding of biological phenomena.”
—Andrea Ablasser
The Approach
The Exploring Innate Immune (In)activities project aims to systematically study molecular checkpoints that control innate immune function. Using an interdisciplinary approach, the researchers seek to identify allosteric sequence motifs within immune receptors and signaling proteins that limit overall activity and control the strength, duration and resolution of immune responses. They will use a combination of structural biology, in silico protein prediction algorithms, biochemistry, and cellular assays to establish a mechanistic understanding of allosteric control at a given site and will classify via in-depth phenotypic analyses in cells and in vivo their impact on cell state and tissue inflammation. The project seeks to generate insights into the rules that govern the functioning of innate immunity and to establish the landscape of the regulatory, evolutionary and therapeutic potential of immune signaling pathways.
Exploring Innate Immune (In)activities is being led by Andrea Ablasser at the Swiss Federal Institute of Technology in Lausanne (EPFL; Switzerland).
Feature image: Airyscan imaging of innate immune stimulated HeLa cells with the nucleus marked in blue.
