Summary of project PR002093
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002093. The data can be accessed directly via it's Project DOI: 10.21228/M82V51 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002093 |
| Project DOI: | doi: 10.21228/M82V51 |
| Project Title: | Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity |
| Project Summary: | Advances in large scale phosphoproteomics and enrichment techniques have improved our capacity to identify an increasing number of phosphorylation sites on metabolic enzymes. While some of these sites are functionally characterized, a systemwide analysis of the phosphorylation-modulated metabolic network remains largely unexplored. Moreover, there exist comprehensive genomic, epigenetic, transcriptomic, proteomic, and metabolite level annotations of metabolic networks, yet there are limited systems level analyses of how phosphorylation events on metabolic enzymes contribute to overall metabolism and network topology. In order to understand the many ways metabolic rewiring can be shaped by perturbations, we need to gain a better perspective of the combined impact of phosphorylation events on multiple metabolic enzymes and their effect on the system. Here we address this challenge by taking a systems approach that integrates computational structural analysis, phosphoproteomics, metabolomics, and biochemical validation of phosphorylation mediated regulation of metabolic enzymes. We specifically interrogate pY on metabolic enzymes using a comprehensive analysis of the in an in vivo model of high fat diet (HFD)-induced obesity where we map out metabolic tuning that alters redox homeostasis. Furthermore, we employ a targeted mass spectrometry-based approach to interrogate pathway specific phosphorylation events and apply computational modeling to identify pY sites associated with altered metabolic output. Lastly, we validate model predictions by measuring the functional role of selected pY sites using a CRISPRi-rescue system with phosphomimic or phosphodeficient enzyme variants in biochemical and isotope tracing metabolomics analysis. |
| Institute: | Massachusetts Institute of Technology |
| Department: | Biological Engineering |
| Laboratory: | Forest White |
| Last Name: | Tamir |
| First Name: | Tigist |
| Address: | 500 Main st |
| Email: | tytamir@mit.edu |
| Phone: | 5717650455 |
| Funding Source: | NIH, NCI, BWF |
Summary of all studies in project PR002093
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003375 | Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity | Mus musculus | Massachusetts Institute of Technology | MS | 2025-03-30 | 1 | 119 | Uploaded data (41.7G)* |
