About the Core
The Proteomics and Post-translational Modification Core supports the goal of understanding the regulation of lysosomal biology by characterization of the lysosomal proteome, post-translational modification (PTM)-mediated signaling, and transcriptional regulation of lysosomal genes. It leverages the expertise and current capacity in the proteomic analysis of subcellular organelles and targeted proteomic characterization and quantitation of protein modification state.
A proteoform is a single molecule species resulting from unambiguously defining all variations in sequence and PTM occupancy, in combination of a single protein molecule. Through the study of proteoforms and determining the percent contribution to the ensemble, it will reveal the functional significance and mechanisms that are otherwise obscured by the limitations of prevailing methods.
The core will provide:
- Robust and reproducible quantitative proteomic analysis of purified lysosomes to enable the study of the lysosomal protein complement multiple projects. This will optimize methods for the sensitive and consistent processing of purified lysosomes for quantitative proteomic analysis. The data generated from this core will be compiled and integrated by the Administrative and Data Integration Core to be integrated into the Aging- and Tauopathy-associated Lysosomal atlas (ATLas).
- Platform for the quantitative analysis of post-translational modifications, proteoforms, and isoforms of lysosome-associated signaling events upstream of transcription. The work done by the core provides the capacity to accurately measure change with unparalleled detail to contribute functional and mechanistic insight for each of the projects of the program.
- Quantitative analysis of histone post-translational modification and proteoforms in support of understanding transcription level mechanisms. With the capability of studying histone PTMs and proteoforms, the core will enable multiple projects investigating the effects on the chromatin regulation system, with single molecule/proteoform specificity and excellent sensitivity.
Core Objectives
- Support all three research projects in this Program Project Grant proposal to elucidate changes in the proteome and mechanism by which protein expression is altered during aging and Alzheimer’s disease.
- Provide robust and reproducible quantitative proteomic analysis of purified lysosomes to enable the study of the lysosomal protein complement multiple projects.
- Provide a platform for the quantitative analysis of post-translational modifications, proteoforms, and isoforms of lysosome-associated signaling events upstream of transcription.
- Provide quantitative analysis of histone post-translational modifications and proteoforms in support of understanding transcription level mechanisms.
