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| Name: |
Gary J. Bassell |
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| Position: |
Associate Professor of Cell Biology
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| Degree: |
Ph.D., University of Massachusetts Medical Center, 1992
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| Programs: |
BCDB,
Full Member
NS,
Full Member
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| Phone: |
404 727-3772 |
| Address: |
405K Whitehead Research Bldg, 615 Michael St, 1941-001-1AF
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| Email: |
gary.bassell@emory.edu |
| Website: |
http://basselllab.com/ |
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Research Descriptions:
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Short:
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Neuronal mechanisms of mRNA transport, local protein synthesis and their dysfunction in Fragile X Syndrome and Spinal Muscular Atrophy.
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Long:
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The major focus of our laboratory is to elucidate the function of mRNA binding proteins and associated protein complexes in the dynamic process of mRNA transport and local translation in neurons. A long-standing interest to us has been the molecular mechanism, regulation and function of beta-actin mRNA transport and local translation within growth cones of developing axons. The mRNA binding protein, zipcode binding protein (ZBP1), was shown to bind to a zipcode sequence in the 3¿UTR of beta-actin mRNA. We discovered that this molecular interaction is required for the dynamic and microtubule-dependent movements of ZBP1 granules containing beta-actin mRNA into axons and growth cones of live neurons (Zhang et. al., Neuron 2001). Ongoing research suggests that ZBP1 may function as a bifunctional adapter molecule that links numerous mRNAs to a specific kinesin motor. We are also studying how axon guidance molecules, such as netrin, regulate local beta-actin synthesis in growth cones to influence growth cone dynamics. The role of mRNA localization and local protein synthesis in nerve regeneration is also under study using in vivo models of nerve injury. Another project is the study of Spinal Muscular Atrophy (SMA), an inherited neurodegenerative disease affecting motor neurons. SMA is caused by the reduction of the survival of motor neuron protein SMN and our recent research indicates a role for a multiprotein SMN complex in the regulation of axonal mRNA. Future plans are to study a mouse model of SMA to characterize possible defects in mRNA regulation and localization. Another project concerns the role of local protein synthesis within dendritic spines and its function in long-term synaptic plasticity. One mRNA binding protein under study is the Fragile X Mental Retardation Protein (FMRP) whose genetic deficiency is the cause of fragile x syndrome (FXS), the most common form of inherited mental retardation. Molecular studies will assess how FMRP modulates mRNA translation in response to glutamatergic signaling. Current research using a mouse model of FXS is to examine the possible role of FMRP in the activity-dependent transport of mRNAs in hippocampal neurons in vivo, applying paradigms relevant to both plasticity and epilepsy. Our research utilizes a multi-disciplinary approach involving imaging, molecular and biochemical methods to study the function of RNA-protein interactions in vitro and vivo.
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