Age-dependent Single-cell Metabolomic and Proteomic Profiling of Human Immune System

With this phase I submissionIsoPlexis proposes to deliver comprehensive profiling of the immune system as a measure of age dependent health in response to medical challenges or traumaThis assay will connect signaling events in the metabolome and proteome from thousands of single cells in parallel enabling the simultaneous tracking of metabolic activity and protein signaling within each immune cell typeFor the purposes of improved health profilingtherapeutic targetingand biomarkers for patient monitoringwe have received incoming demands for this novel assay from translational centers and biopharma that are focused on the aging immune systemIn the normal aging processthe relative abundance of na ve T cells decreases while highly differentiated effector and memory T cells increaseFunctional genetic analysis of whole blood indicates global changes in immune gene signaling as well as metabolic functioning as a consequence of ageHoweverdeciphering these changes into meaningful impact on human health in the aging immune system requires higher resolution analysesIsoPlexis has exclusively licensed the publishedunderlying metabolomics technology from our collaborator and scientific advisor Jim Heath who devised a methodology to combine detection of metabolites with proteomic profiling of intracellular signaling pathways and cytokine production in single cellsThe Heath lab established uniquely combined metabolite competition capture assays with sensitive signal transduction protein captureto help uncover unique pathways and potential treatment targetsUnderstanding that this development has broad human health applicationcell specific metabolic and proteomic markers as a function of agecalibrated immune system performance will guide patient response to improved personalized therapiesA new general immune health assay is needed that canimake highly multiplexed measurements from single cellsiiwhile being able to gather both proteomic and metabolic information from the same celliiiin a manner that is high throughputWe propose to use this phase I grant to allow IsoPlexis to develop an integratedautomated single cell metabolomic proteomic platformas a comprehensive immune health assessment to better calibrate new personalized medical treatmentsAimDevelop and optimize an expanded metabolite capture library onchip and integrate with intracellular proteomic assays targeting the immune system as it maturesAimDevelop methods on automated platform for monitoring single cell metabolomic proteomic biomarkers responding to environmental stressors to evaluate immune system metabolic resilienceTransition to phase IITo demonstrate the combined metabolomic proteomic assay valuewe will evaluate a sampling from an ethnically diversegenetically characterized pool that our collaborators at Columbia University are collecting to advance unique metabolomic and proteomic immune profilesAdditionallythe multiplexed metabolomic proteomic assay will be integrated onto our automated platform for commercial use Aging significantly impacts the cell metabolism or energy consumption of the immune system and affects immune cells to rapidly recover from the various types of challengesTo comprehensively understand what factors are driving cell resilience in aged individualswe aim to develop a method to measure energy consumption and effector secretion simultaneously at single cell levelMining metabolomic information together with protein secretionwhich drives cell resilience of the aging immune system will enable the development of restorative therapies in the future