Understanding the molecular mechanisms underlying synaptic plasticity
Dr. Barbee's research uses the fruit fly Drosophila melanogaster as a genetic model system to address several problems directly related to human health:
Dr. Barbee studies the basic molecular mechanisms underlying memory formation under non-pathological and pathological conditions. The latter include memory disorders such as the gradual loss of memory associated with age, dementia, Alzheimer's disease and the cognitive defects associated with some forms of mental retardation, addiction, and mental disease. Current projects include identifying and characterizing novel regulatory factors (protein and miRNAs) involved in the control of local mRNA translation in response to synaptic stimulation. The rationale is that these factors (and their target mRNAs) may prove to be uncharacterized therapeutic targets for the prevention or treatment of a variety of memory disorders.
DRUG and ALCOHOL ADDICTION
Addictive drugs are thought to cause persistent changes in synapse structure and function by co-opting existing machinery underlying the formation and maintenance long-term memory. It is widely accepted that long-term synaptic plasticity, a cellular correlate of learning and memory, is mediated by activity-dependant gene transcription and protein synthesis. New evidence suggests that the miRNA pathway plays an important role in the control of these processes. Dr. Barbee is currently funded by a grant from the National Institute on Drug Abuse (NIDA) at the National Institutes of Health (NIH) to identify and characterize novel miRNA-mediated mechanisms that may be involved in the pathology of drug abuse and addiction.
FRAGILE X SYNDROME and AUTISM
Fragile X Syndrome (FXS) is the most common form of inherited mental retardation in humans and is a major genetic cause of autism. FXS is characterized by an array of intellectual and emotional problems including learning disabilities, developmental delay, and anxiety. FXS is caused by the reduction or loss of expression of a RNA-binding protein called FMRP. However, the precise mechanisms by which loss of FMRP lead to the manifestation of FXS remains largely unknown. New evidence suggests that FMRP controls the expression of target mRNAs through the miRNA pathway. Dr. Barbee's laboratory has recently found that FMRP may be targeting some neuronal mRNAs for miRNA-mediated degradation. Work is currently underway to identify novel FMRP-associated miRNAs and characterize their target mRNAs.