The brain is widely considered to be the most complex organ that evolution has ever produced. No organ (or tissue, or cell for that matter) from any species, develops in a vacuum. Developing organs are under constant bombardment from a host of extrinsic factors. We are insanely interested in understanding how environmental factors affect the developing brain. We want to know how it is possible for neurons to integrate and respond to these factors, many of which may be present one moment and disappear the next. We also want to know how the brain is able to regulate synaptic connectivity under such dynamic circumstances.
In our quest to unravel the complicated intertwining of genetics and environment, we employ multiple experimental strategies.
flies
Drosophila are a powerful tool for understanding the evolutionary conserved mechanisms of developmental biology. As fly geneticists, we exploit over 150 years of fly research to understand what makes neurons develop, grow, project, retract, and die. We want to know how neurons communicate with each other through synapses and similarly what mechanisms cause those synapses to develop and die. All of our lines of questioning are framed in the context of the impact of environmental factors on these critical developmental processes.
We are currently using the Drosophila model of Fragile X Syndrome (see below) to understand how environmental trace elements affect developing neurons in this disease. This model allows us to manipulate specific genetic elements in the context of different environmental exposures. We then use a variety of molecular, cellular, and behavioral assays to determine how these different conditions affect neuronal connectivity in both the peripheral and central nervous systems of the fly. Due to the strong evolutionary conservation of genes between flies and humans, we expect our work will shed new light on the role of trace elements in both Fragile X Syndrome and normal brain development.
Useful Resources
humans
Fragile X Syndrome (FXS) is the most common form of inherited mental disability and the leading known genetic cause of autism. FXS patients suffer from a host of developmental conditions including attention deficit disorders, hyperactivity, sensory hypersensitivity, and extreme anxiety. These symptoms can vary widely across FXS patients but the source of this heterogeneity is unclear.
FXS is caused by the loss of function of a single gene, FMR1, which regulates a diverse group of cellular processes including RNA metabolism and protein translation. Many labs across the globe are attempting to dissect these pathways in the hope of discovering potential therapeutic interventions. Despite these tremendous efforts, there is no known cure for FXS.
Our research is a collaboration with Dr. Craig Erickson at Cincinnati Children's Hospital Medical Center. All current treatments for FXS and autism are focused on relieving individual symptoms, and the successes or failures of these treatments are often measured by somewhat subjective criteria. Together with the Erickson group, we are attempting to uncover molecular biomarkers of these related diseases so that more accurate diagnoses can be made at the outset, and more objective evaluations can be made of potential therapies.
