LipTransProMet · The multi-omics role of lipid transfer proteins in lipid metabolism
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-04-01 → 2021-03-31
- EU contribution
- €162,806
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
The multi-omics role of lipid transfer proteins in lipid metabolism
Cellular membranes of eukaryotic cells vary in their lipid composition, which allows segregation of diverse biological processes and specific enrichment of signaling, enzymatic and structural proteins. Differential enrichment of lipids in different membranes allows segregation of diverse biological processes and depends on lipid transport between membranes. Lipid transfer proteins (LTPs) facilitate non-vesicular lipid transport through aqueous spaces, and their dysfunction can lead to diseases, because of centrality in many cellular functions. For the majority of the >100 LTPs in humans, lipid cargoes, metabolic integration, mode of action, and targeted organelles remain unknown. As primary objective, we explored the role of the LTPs in lipid metabolism. We integrated proteomics and lipidomics data from lipid mobilization screens with previously published data and data from public databases, also evaluating LTP cooperation for more complex biological functions. We aimed for general network biology insights and identified lipid metabolic pathways relying on the LTPs. As secondary objectives, we identified involved organelles, obtained individual protein and lipid insights, and found and acted upon synergies with other research, leading to collaborations further broadening the scientific and societal impact.
Data: CORDIS, © European Union
Project objective
Cellular membranes of eukaryotic cells vary in their lipid composition, which allows segregation of diverse biological processes and specific enrichment of signaling, enzymatic and structural proteins. Differential enrichment of lipids in different membranes stems from compartmentalized synthesis and degradation of lipids, but also from lipid transport between membranes. Lipid transfer proteins (LTPs) facilitate non-vesicular lipid transport through aqueous spaces, and their dysfunction can lead to diseases. They are crucial for many molecular processes because a large part of the proteome depends on membranes for its function. However, for the majority of the more than 100 LTPs in humans, the lipid cargoes, the integration into metabolism, the mode of action, and the targeted organelles remain unknown. The Gavin group recently performed large screens to identify the lipids bound and transported by LTPs, and during my first months in the host lab, I have been involved in the data analysis of these screens.Our primary objective in the current project is to take the next step by exploring the role of LTPs in lipid metabolism. We will evaluate the effect of LTP knockdown in cell lines with a unique combination of two complementary systems biology approaches: lipidomics and thermal proteome profiling. The integration of these data with previous data from the Gavin group and public databases will highlight lipid metabolic pathways that rely on LTPs for their correct function, and might decipher less obvious connections with other cellular pathways. Moreover, as additional results of this analysis, these data will likely also highlight relevant organelles and maybe even signaling pathways, even further establishing the functions of the LTPs. This project will enhance our insight in the role of non-vesicular transport in lipid metabolism, while the new approach is likely broadly applicable, even for the future study of primary cells from patients.
Original text from CORDIS.
Participants
- EUROPEAN MOLECULAR BIOLOGY LABORATORY · HeidelbergCoordinatorGermany
Links
Data: CORDIS, © European Union