Project title: Complement dependent long non-coding RNA

The complement system drives inflammation and cues leukocyte cellular differentiation in runaway infections such as septicemia and severe Covid-19 that can cause tissue damage and death. PAMP (pathogen-associated molecular patterns) activation in severe inflammation is well understood for mRNA and proteins. However, long non-coding RNAs (lncRNAs) have emerged as key regulators of transcription, splicing, translation and epigenetic reprogramming to assist cell differentiation in innate and acquired immunity. The lncRNAs integrate the immune response by forming interactions with DNA, RNA and proteins. Our project study lncRNAs in a human whole-blood model (WBM) where we can add pathogens such as Staphylococcus aureus (SA) and E. coli. With the WBM, it is easy to block key components of the immune system, such as the CS, the inflammasome and other targets of interest to gauge its effects on lncRNA expression when induced with pathogens or other relevant stimuli. The project aims to identify the complexes formed between lncRNA and proteins when pathogens cause an inflammatory response using RNA antisense purification and quantitative mass spectrometry (RAP-MS). This knowledge can be used to disrupt the RNA-protein interaction for therapeutic use in severe inflammation.