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”)