The role of stress genes in aging
My lab is
interested in understanding how stress response genes like the p38 MAPK (p38K)
regulate the aging process. We have previously found that over-expression of
p38K leads to a 37% increase in lifespan as well as resistance to exposure to
oxidizing agents like paraquat, a pesticide that has been linked to causing
Parkinson’s disease. Loss of p38K results in a severely shortened lifespan,
increased sensitivity to oxidizing agents, and accelerated age-dependent
locomotor behavior dysfunction (Vrailas-Mortimer, et al. 2011 and Vrailas-Mortimer, et al. 2012). We are now testing
what are the mechanisms by which p38K regulates the aging process.
Aged Control Flies
Video 1. Wild type (control) flies have normal climbing behavior at 3 days of age (Vrailas-Mortimer, et al. 2011).
Aged Mutant Flies
Video 1. By 3 days of age p38K mutant (control) flies have trouble climbing (Vrailas-Mortimer, et al. 2011).
The role of stress genes and
pesticide exposure in Parkinson's disease
is the leading risk factor for the development of a neurodegenerative disease
like Parkinson’s disease (PD). In addition, high levels of oxidative stress
have been associated with the loss of dopaminergic neurons (the hallmark of
PD). Therefore, we are exploring how genes, which regulate both aging and
oxidative stress, contribute to PD.
Figure 1. Dopaminergic neurons
in the adult Drosophila brain. When a person loses about 80% of these neurons,
the classical motor symptoms of Parkinson's disease usually become present.
Similar locomotor problems also occur in fly models of Parkinson's disease.
The role of protein homeostasis in Muscular Dystrophies
homeostasis is the process by which the quality/functions of the proteins in
the cell are maintained. Disruptions in protein homeostasis can lead to the
accumulation of damaged proteins that no longer function properly, thus leading
to tissue degeneration. Both aging and increased levels of oxidative stress can
disrupt protein homeostasis and have been associated with certain forms of
muscular dystrophy such as the Limb-Girdle Muscular Dystrophies (LGMD). We are
testing how mutations in genes associated with protein homeostasis may be
contributing to LGMD.
Figure 2. Protein aggregates in the Drosophila flight muscle.
Copper toxicity and
is a complex brain disorder with no known cause. Though a variety of genes have
been implicated in schizophrenia, it is thought that gene x environment
interactions may play an important role in the development of this disorder. We
have an on-going collaboration with Dr. Victor Faundez at Emory University to
explore how changes in copper homeostasis (the process of maintaining proper levels of cellular copper) may contribute to schizophrenia (Gokhale, et al. 2015).
Figure 3. The adult Drosophila brain consists of active synaptic sites (nc82 in red), glial cells (repo in red), neurons (elav in red) and the mushroom bodies (centers for higher learning and memory, FasII in red).