Phospholipid detection in Traumatic Brain Injury and Alzheimers disease

Regulation of phosphoinositides, especially the tightly regulated signaling lipid, phosphatidylinositol(4,5)-bisphophate [PI(4,5)P2], have been implicated in Alzheimers disease (AD) and traumatic brain injury (TBI). We propose to study the temporal and spatial acc,umulation of PI(4,5)P2 in an optogeneitcly stimulated synthetic paradigm. We wil also determine the content of phosphoinositides in,human AD and TBI brain tissues and biofluids. This work is currently funded by Department of Defense Peer Reviewed Alzheimer's Resea,rch Program Convergence Science Research Award, McIntire (PI), Title: Optogenetic Regulation of Phosphoinositide Metabolism in Susce,ptibility, Resistance, and Resiliency to Alzheimers DiseaseAssociated Deficits and Pathology. To support these DOD funded efforts,, we propose to acquire ThermoFisher Integrion Ion Chromatography with Eluent Generation Quote $54,223.96. This instrument is state o,f the art used for ion chromatography and separation of polyphosphorylated species of phosphoinositides. This unique methodology is,necessary for detection of anionic lipid species which cannot easily be isolated and quantified using other methods such as mass spe,ctrometry due to their isobaric characteristics. For example, phosphatidyl inositol with two phosphate groups on the inositol ring c,an occur as phosphatidylinositol 4,5-bisphosphate or phosphatidylinositol 3,5-bisphosphate. Each of these lipids has dramatically di,fferent cell signaling properties and metabolic profiles. Multiple groups have the need to separate and quantify the abundance of th,ese lipids in multiple experimental models including cell lines, mouse brain and human brain biospecimens. Acquisition of this instr,ument will facilitate collaboration in our institute as well as provide a unique methodology which can be applied across fields prov,iding feasibility for innovative research programs and grant applications that could not be accomplished without this instrumentatio,n. Further this unique and highly specialized methodology and expertise in phosphoinositide metabolism is often sought by collaborat,ors external to the institution leading to productive and innovative advances in the field. This instrument will augment our researc,h environment and support collaborative research and quantification of phosphoinositide lipid species which is not possible without,the ThermoFisher Integrion Ion Chromatography with Eluent Generation.