CE44 - Biochimie et chimie du vivant

Programming condensates to sequester lipid droplets in cells and control their metabolism – ControLD

Submission summary

Lipid droplets (LDs) are unusual cellular organelles that are at the nexus of cellular lipid metabolism. In addition to carbon and energy storage, they play major roles in various processes such as lipid metabolism, protein storage and degradation, as well as resistance to biotic and abiotic stress. In human, they are involved in various metabolic disorders, while in plants, they raise interest for biotechnological applications. A better understanding of LD biology is thus crucial both for health issues and green biotechnologies. In particular, the spatiotemporal control of LD biogenesis and functions to coordinate response to metabolic need, stress, and cell fate, remains poorly understood. In addition, methods to probe and dissect LD dynamics and functions in cells remain underdeveloped. Therefore, the elaboration of new methodologies to probe and perturb LDs in cells is essential. Here, we have built a unique interdisciplinary consortium with synergetic expertise in biochemistry, protein engineering, biophysics and cell biology aiming to provide a novel tool to manipulate LDs in cells. We propose to develop and use a novel tool allowing to perturb and probe LD dynamics in living cells. Our strategy is to engineer artificial condensates associated with LD proteins. We aim to use such condensates as a protein-based polymeric meshwork that will grow specifically around lipid droplets. This method will be applied to study LD biology as well as create a new platform to identify LD composition.
In the ControLD project, we will therefore:
(1) Develop a methodology to trigger the controlled formation of artificial condensates programmed to spatially reorganize and sequester LDs in cells.
(2) Quantify how LD sequestration perturb their dynamics in human cells and use the LD-targeting condensates to facilitate the extraction and characterization of LD subpopulations.
(3) Address the perturbations of LD dynamics in the model microalga Phaeodactylum tricornutum (Pt) and how this affects the microalgae fitness in normal conditions or upon abiotic stress.
In summary, the project will provide the community with new tools for the study of LD in various systems. Moreover, it will provide novel knowledge in human cells and microalgae regarding the dynamics of LDs in vivo, the composition of LD subpopulations, as well as regarding LD biological functions in various conditions.

Project coordination

Zoher GUEROUI (Ecole Normale Supérieure Paris)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LPENS Ecole Normale Supérieure Paris
PASTEUR Ecole Normale Supérieure Paris
LPCV Institut National en agriculture environnement et alimentation

Help of the ANR 601,891 euros
Beginning and duration of the scientific project: March 2023 - 42 Months

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