Pathogenomics of innate immunity: analysis of the roles of TNIP1, DUSP16, and TANK in toll-like receptor signalling, innate immunity and inflammation, using novel gene-knockout mice

When disease-causing microorganisms breach the body’s external defences, protective mechanisms of innate immunity are rapidly activated. These are essential to control and clear the infection, but can also contribute to tissue damage. Uncontrolled or inappropriate activation of innate immunity can cause chronic inflammatory disorders, such as arthritis, or result in a highly-dangerous state of acute inflammation, known as sepsis. Thus, a detailed knowledge of innate immunity is critical for understanding the mechanisms regulating inflammation and the causes of human inflammatory diseases. It is also essential if we are to develop therapies that artificially boost innate immunity to cure infections, without inducing damaging inflammation. Activation of innate immunity is critically dependent on several classes of receptor-proteins, which detect infections by selectively binding microbial compounds. Toll-like receptors (TLRs) are one of the most important classes of such proteins, activating a cascade of events that is an essential part of the early phases of innate immune response. Previous research has identified a set of genes, believed to be important regulators of TLR signalling, innate immunity and inflammation. As part of a large, multinational research program, Dr. Anastasiya Nyzhnyk is focusing on three of these genes: TNIP1, DUSP16 and TANK. Using mouse models and human cell lines, she is analyzing how the inactivation of these genes affects TLR signalling, and studying the resulting molecular, cellular, and physiological effects. Her work is expected to expand knowledge about early immune responses to infection, and may lead to a better understanding of the causes of inflammatory diseases and suggest new strategies for their therapy