Objective
"The 5' adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of cell energy metabolism. AMPK (dys)regulation has been connected to metabolomic disease, conditions of the heart and viral infections. AMPK is fine-tuned through its structural features, which are dependent on mRNA isoform splicing, protein complexation, post-translational modification (PTM), and allosteric activation . AMPK’s diverse regulatory role is deeply connected to its post-translational modifications (43 known phosphorylation and 36 known other PTM sites). The result of this structural diversity is an extremely large combinatorial space of (1) unique covalently modified α-β-γ isoforms, the proteoforms, and (2) their unique non-covalent assemblies, the complex species. However, the structural diversity of AMPK is not well understood. The goal of this project is to to study the modifications and endogenous diversity of AMPK proteoforms and complex species from a ""bird's eye view"", depicting and mapping in parallel existing complete length AMPK forms, using denatured and native Top-down Mass Spectrometry (TDMS).
-Outgoing phase, Ying Ge Lab, University of Wisconsin-Madison (UWM) (M1-24): Recombinant AMPK complex to study coded proteoforms (O1-2) and establish a strategy for purification of endogenous AMPK (O3).
-Incoming phase (M25-36), Charlotte Uetrecht Lab, University of Lübeck (UzL): Transfer learned technologies and map endogenous AMPK proteoforms in different tissues (O4). Design endogenous-ike AMPK proteoforms (O2).
-Non-academic phase (M37-42) Bruker Daltonics GmbH (BRUKER): Close gaps in data acquisition and get more out of AMPK with next-gen MS instruments (O2).
The aspired methodology and results will be important for the identification of AMPK biomarkers and, ultimately, for the advancement of precision medicine, where treatment is tailored for the individual molecular setup of a patient subgroup such as in metabolomic or heart disease."
Fields of science
Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-GF - HORIZON TMA MSCA Postdoctoral Fellowships - Global FellowshipsCoordinator
23562 Lubeck
Germany