Long non-coding RNA as a fine tuner of fat cell function.

Energy is stored in the form of triglyceride ready for breakdown into fatty acids (FAs) and release into the circulation.

In obesity, the adipose tissue dysfunctions, resulting in high spontaneous release and low capacity for further FAs mobilization in states of demand.

Chronic release and elevation of systemic FAs is a major driver of type-2 diabetes pathogenesis.My research will understand how long non-coding RNAs (lncRNAs) function throughout the adipocyte to control lipid storage and contribute to the dysregulated FAs release in obesity.

I have developed methodology to study lncRNAs in human fat cells including a novel beyond-state-of-the-art technique to identify the specific interacting proteins, termed TROOPS.I will use unique and extensive clinical white adipose tissue biopsy data to identify disease regulated lncRNAs.

I will map how these lncRNAs function in human adipocytes using cutting-edge gene editing techniques and lipid/metabolomics.

Coupling protein-lncRNA complex purification with electron microscopy, I will understand how lncRNAs function at a molecular resolution.

Finally, using large population genomics and genetic variant base-editing in patient derived adipocytes, I will identify causal variants in lncRNA loci driving cardiometabolic disease.

The results will provide a shift in understanding for how lncRNAs enable the adipocyte to perform specialized lipid handling functions and how alterations in these lncRNAs leads to maladaptation.