Neutrophils are the most abundant type of immune cell in the human body. One of the most important functions carried out by neutrophils is a process called NETosis, in which neutrophils self-destruct, spilling out their cell contents, including their DNA, to trap nearby pathogens and promote local inflammation. Abundant NETosis worsens cardiovascular, autoimmune, and neurodegenerative diseases. A key step of NETosis is the decompaction of chromatin, the tightly compacted complex of DNA and proteins that resides inside the nucleus of the cell. However, despite its critical importance for human health, our mechanistic understanding of chromatin decompaction during NETosis remains very limited. Here, we aim to address this gap in fundamental knowledge by applying the Altemose Lab’s cutting-edge DNA sequencing technologies to the Thiam Lab’s highly controlled system for inducing and measuring
NETosis. By understanding the molecular mechanisms driving chromatin decompaction in NETosis, this work has the potential to uncover new therapeutic targets for regulating NETosis in human disease. Beyond NETosis, success will challenge a dogma in chromatin biology that equates open chromatin with gene expression, opening the door to understanding and tuning the role of open chromatin in other health-relevant cellular functions such as proliferation or stem cell differentiation.