The European Research Council (ERC) has awarded two grants to researchers at the UMC Utrecht. Radiologist Jeroen Hendrikse and microbiologist Suzan Rooijakkers each receive 1.5 million euro for the next five years to establish a research line of their own. The ERC Starting Grant is considered a major grant and is awarded annually to a select group of promising researchers.
In his research Jeroen Hendrikse focuses on the cause of stroke. Brain microinfarcts and macroinfarcts cause a major healthcare burden in Western societies both in terms of morbidity and costs. Cardiovascular thromboemboli from the heart, aorta and neck arteries are considered as the main cause. Still, the vast majority of brain infarcts are unexplained. Hendrikse will establish advanced MRI-techniques to visualise and quantify local atherosclerotic plaque of the small intracranial arteries around the circle of Willis and impaired brain perfusion. Shedding light on the pivotal role of intracranial atherosclerosis and perfusion deficits on brain parenchyma damage will pave the way for designing preventive and therapeutic strategies aimed at reducing the burden of stroke and neurodegenerative diseases.
With her research Suzan Rooijakkers aims to provide insight into how bacteria are killed by the complement system, an important part of the host immune response against bacterial infections. Complement is a large protein network in plasma that labels bacteria for phagocytosis and directly kills them via the formation of a pore-forming complex (Membrane Attack Complex (MAC)). Currently it is not understood how complement activation results in bacterial killing. This knowledge gap is mainly caused by the lack of tools to study the enzymes that trigger MAC formation: the C5 convertases. Rooijakkers lab recently established a novel assay system for C5 convertases to study these enzymes under purified conditions.
With biochemical, structural and microbiological approaches she will elucidate the precise molecular arrangement of C5 convertases in vitro and on bacterial cells and generate unique tools to study how C5 convertases regulate MAC insertion into bacterial membranes. Finally, she will engineer fluorescent bacteria and labeled complement proteins to perform advanced microscopy analyses of how MAC kills bacteria.
These insights will create new avenues for blocking the undesired complement activation during systemic infections and acute inflammatory processes. Furthermore this knowledge will improve desired complement activation by therapeutic antibodies and vaccination strategies in infectious diseases.