led by Jordan D Dimitrov
Investigation of the physicochemical mechanisms of antibodies specificity and polyspecificity. Molecular mechanisms and biological consequences of the interaction of antibodies with low molecular weight cofactor molecules.
The group “Canonical and non-canonical functions of immunoglobulins” (head: Jordan Dimitrov) focuses on interdisciplinary studies on human antibodies. By employing methods typical for molecular biophysics, biochemistry and immunology, we elucidate the mechanism and biological significance of antibodies with conventional properties as well as those with untypical properties and activities, including promiscuous antibodies, self-binding antibodies and antibodies that interact with low biological cofactor molecules such as ATP, heme and metal ions. The principal objective of these studies is to delineate conventional and non-conventional activities of antibodies in the context of physiological immune responses against pathogens as well as antibody functions under non-infectious pathological conditions (hemolytic diseases, cancer). We will exploit our pipeline for cloning, expressing and engineering of human antibodies from single human B cells. We will also exploit novel biochemical assays for early detection of biophysical liabilities of candidate therapeutic antibodies. The ultimate goal of these studies is to use fundamental knowledge for the rational engineering of antibodies and harnessing their activities for targeting infections agents, pro-inflammatory molecules as well as cancer cells.