The Role of FLAP-5-LO Complex in Curvature Formation at Neutrophil Nuclear Envelope Using Electron Microscopy


Inflammation is part of our immune response to pathogen invasion, and neutrophils, AKA white blood cells, are the first cells to respond. Unfortunately, it is more of a bane than boon. Now more research studies suggest that inflammation is a common causative factor in many diseases including respiratory and cardiovascular diseases. These diseases share a common nexus - leukotrienes. Arachidonate 5-lipoxygenase (5-LO, the green blob in the image) and the integral membrane protein 5-LO activating protein (FLAP, the yellow blob is a FLAP trimer) are key for leukotriene B4 synthesis in neutrophils. The FLAP inhibitors have been shown to be effective in chronic asthma clinical trials and prevention of cardiovascular diseases in animal models. The research study from Dr. Carole A. Parent lab at the University of Michigan is indicating that FLAP and 5-LO are not only functionally important for leukotriene B4 synthesis but also structurally critical for its packaging and release through vesicular carriers. In collaboration with Dr. Melanie Ohi lab, we aim to explore the role of these two proteins in the formation of leukotriene B4-containing vesicles from the neutrophil nuclear membrane by using state-of-the-art negative staining electron microscopy and cryo-electron microscopy. We envision that the results will be informative for the future treatment of the inflammatory diseases.