Our research topic

Nutrient sensing enables metabolic homeostasis by matching energy use with fuel availability. The vast body of knowledge on pro-anabolic nutrient sensors, such as insulin and phosphoinositol-3 kinase (PI3K) signalling exposed the missing links in molecular coordination of catabolism. The cellular catabolism relies on mitochondrial activities and on lysosomal pathway of autophagy, both paced by the biological clock. We are interested in understanding how PI3K nutrient sensors synchronize metabolic activities in healthy tissue and what are the consequences of their dysfunction in human disease.

We focus on class 3 PI3K, the only PI3K present in all eukaryotes. We have discovered its essential function for catabolic homeostasis in vivo. In on-going projects we seek to:

· Identify the regulatory complexes of class 3 PI3K that serve its catabolic integrator function

· Reveal the physiological regulation of class 3 PI3K and its reciprocal impact on metabolic timekeeping

· Discover genetic alterations in class 3 PI3K signalling in inborn metabolic diseases

· Translate our mechanistic findings to treatment of human diseases


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