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Alysia Vrailas Mortimer
Alysia Vrailas Mortimer
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​Research

Overview

 

            My research focuses on how different factors such as aging and exposure to toxins (pesticides and heavy metals) contribute to neurological disorders and muscular dystrophies. A common feature of aging, exposure to toxins, and many diseases is increased levels of oxidative stress (oxygen radicals that are highly damaging to DNA, proteins, and other cellular structures). Therefore, my lab explores how stress response genes play a role in regulating aging and toxin exposure and how this contributes to a disease state. In order to address these questions, we use the genetic model organism Drosophila melanogaster (fruit fly), which has been instrumental in our understanding of many neurological and muscle disorders.​​

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. 

 

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                         Aged Control Flies

Video 1. Wild type (control) flies have normal climbing behavior at 3 days of age (Vrailas-Mortimer, et al. 2011).

 

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                           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

Age 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. 


     Dopaminergic Neurons in the adult fly brain

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


Protein 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.  
      protein aggregates in the fly muscle.jpg
  Figure 2.  Protein aggregates in the Drosophila flight muscle.


Copper toxicity and Schizophrenia

Schizophrenia 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​).

                               synapses, glia, neurons and mushroom bodies in the fly brain.jpg
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).