Biosynthesis and physiological role of endogenous mammalian “phytohormones” in health and disease

Some secondary metabolites have long been known to act as signaling molecules in plants. Many of
these “phytohormones” are however produced by a wide range of organisms, including humans.
Two very interesting phytohormones that are produced in humans are abscisic acid (ABA) and
salicylic acid (SA), which both show anti-inflammatory properties. SA is best known as the active
component of Aspirin, but SA has actually been used as a medicine against inflammation and pain
for at least 3,500 years. Its anti-inflammatory properties are thus well-documented. Despite this, we
do not know when and how ABA and SA are produced in humans and what is their physiological role
in homeostasis and disease. Serum SA and ABA levels will be measured in mice and cells challenged
with different inflammatory stimuli or subjected to experimental disease models. Since SA and ABA
biosynthetic pathways are unknown, we will initially use transgenic mice expressing enzymes that
degrade SA or ABA in order to investigate the physiological roles of basal and stimulated production
of SA and ABA. In parallel, we will try to identify the genes responsible for SA and ABA biosynthesis,
which could lead to the discovery of novel SA and ABA deficiency-dependent diseases.