Coping with a stressful start in life

Joint Seminar with the Dunn School

Environmental stresses experienced during development (early-life) exert both short
and long-term influences upon health and disease. In most cases, however, the
underlying biological response mechanisms remain mysterious. The goal of our
research is to understand the molecular nuts and bolts of how early-life environmental
stresses alter gene expression, metabolism and physiology. Much of our research uses
the powerful genetics of the fruit fly Drosophila, together with analytical techniques
such as metabolomics and mass spectrometry imaging. Using this combined approach,
we identified molecular mechanisms that protect neural stem cells in the developing
CNS from the immediate harmful effects of malnutrition and hypoxia. For example, we
found that hypoxia induces lipid droplets in the local microenvironment (niche) of the
neural stem cells. Droplets function to protect neural stem cells from lipid peroxidation
damage, likely by sequestering potentially vulnerable polyunsaturated fatty acids in
their core. We have also begun investigating the longer-term impact of early-life
stresses upon longevity. Recent work shows that developmental exposure to mild
oxidative or nutritional stress can, in some cases, extend rather than shorten lifespan.
I will discuss the surprising mechanisms that account for stress-induced longevity and
the degree to which they may be conserved between flies and mammals.