1. Diabetes, the most infamous aspect of metabolic syndrome, represents a growing problem in developed countries. It is a complex disease whose onset is not yet fully understood. It encompasses diverse aspects of cellular metabolism and signalling, with insulin-mediated signalling being the best characterized.

Since decades zinc, an essential micronutrient, has been recognized as important for proper insulin synthesis, secretion and signalling, with reduced zinc status often being associated with diabetes. Lately however, amounting evidence points to a more widespread role of zinc homeostasis and zinc-mediated signalling in lipid metabolism. A few years ago a novel player has been added to the already intricate story – the adipocyte secreted hormone adiponectin and its membrane receptors. In humans, adiponectin levels are positively associated with insulin sensitivity and inversely related to the degree of adiposity, and recently it has been shown in animal models, that high-fat high-sucrose diet-induced diabetes is associated with defects in adiponectin receptor expression.

In yeast, there are four adiponectin receptor homologs – Izh1, Izh2, Izh3 and Izh4 (also referred to as the IZH gene family). They were first annotated as being Involved in Zinc Homeostasis. Besides altered zinc levels, they also respond to fatty acids and high glucose and are involved in lipid and phosphate metabolism. Their exact role and underlying signalling, however, is still a blur.

The aim of my project is thus to determine, with the use of high-throughput genetics methods, bioinformatics, biochemical, molecular and cellular biology techniques, what the role of zinc and the IZH genes in lipid metabolism is, how are they connected and how the signal is being relayed. The findings should contribute to the understanding of diabetes and other obesity-linked diseases. The conservation of the involved molecules from yeast to humans makes yeast a perfect model organism to approach the problem.

(Currently waiting for the youngsters to finish their high-throughput experiments, so I can play around with the data, which will inevitably end up with me saving the world from an awful disease and winning the Nobel Prize)

 

2. Using yeast as s model organism to study the biology and mechanism of action of PLA2s. (a.k.a. “travelling around the world, learning new fancy techniques, mingling with hot shots”)