Understanding how long non coding RNAs adapt the adipocyte for specialised lipid...
Understanding how long non coding RNAs adapt the adipocyte for specialised lipid storage and breakdown.
Energy is stored in adipocytes as a large uniocular lipid droplet, which can be broken down into fatty acids (FAs) and released into the circulation when needed. This specialised lipid storage and breakdown requires dynamic organi...
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31/12/2029
KI
1M€
Presupuesto del proyecto: 1M€
Líder del proyecto
KAROLINSKA INSTITUTET
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Fecha límite participación
Sin fecha límite de participación.
Financiación
concedida
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el día 2024-10-09
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Información proyecto LNC-LIPID
Duración del proyecto: 62 meses
Fecha Inicio: 2024-10-09
Fecha Fin: 2029-12-31
Líder del proyecto
KAROLINSKA INSTITUTET
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Presupuesto del proyecto
1M€
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
Energy is stored in adipocytes as a large uniocular lipid droplet, which can be broken down into fatty acids (FAs) and released into the circulation when needed. This specialised lipid storage and breakdown requires dynamic organisation of metabolic enzymes and cofactors around the large lipid droplet for metabolic homeostasis. In obesity, the adipocyte dysfunctions, resulting in high spontaneous release of FAs. This chronic release and elevation of systemic FAs is a major driver of systemic insulin resistance, type 2 diabetes and other cardiometabolic diseases.
I postulate that long non-coding RNAs (lncRNAs) interact with the metabolic machinery within the adipocyte to organize cell- and stimulation-specific interactomes, channelling substrate flux within the cell. Adipocytes express over 4000 lncRNAs, many of which are unique to humans and this cell type. However, whether these lncRNAs contribute to the adipocyte’s specialised lipid metabolism in health and disease is not understood. This proposed research aims to address this question.
I have already developed key methodologies to study lncRNAs in human adipocytes, including a novel technique called TROOPS that identifies specific lncRNA-interacting proteins. Leveraging an extensive bank of white adipose tissue biopsies from uniquely characterized patients, I will identify disease-regulated lncRNAs and test how they function in human adipocytes. I will use gene editing techniques and lipid/metabolomics analysis to define the role of these lncRNAs in lipid storage and FA release.
Furthermore, I will use protein-lncRNA complex purification combined with advanced microscopy techniques to reveal how lncRNAs can sequester protein complexes into phase-separated organelles and organize adipocyte lipid metabolism. These insights will provide a paradigm shift in understanding how lncRNAs enable the adipocyte to perform specialized functions and new generalizable findings for how lncRNAs contribute to cell function.