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George, Julia M.
Assistant Professor, Molecular and Integrative Physiology and Neuroscience
B.S. Texas A&M University
Ph.D. 1993 The Rockefeller University
Research Areas
Synuclein proteins and neurodegenerative disease
The synucleins are a family of small, highly conserved proteins enriched in the vertebrate brain. Expression of α-synuclein (AS) is upregulated in association with song acquisition in zebra finch. Mutations in the protein cause a rare inherited form of Parkinson‘s disease, and AS aggregation is associated with sporadic Parkinson‘s and a number of other neurodegenerative disorders (Alzheimer‘s disease, dementia with Lewy bodies, multiple system atrophy, Down‘s syndrome).
My laboratory is applying a combination of molecular, biochemical, and cell culture approaches to determine the normal function of AS in neurons, and to elucidate the factors that influence pathological aggregation of AS. We have reported that AS is a lipid-binding protein with structural similarity to the exchangeable apolipoproteins, and that membrane binding leads to a major shift in protein conformation, from random coil to α-helix. We hypothesize that this change in conformation serves as a functional switch, and are currently pursuing several projects that focus on the interaction between synuclein and membranes as the key to its function:
Analysis of the structural determinants of phospholipase D2 inhibition by synucleins.
Phage display to identify peptides that influence the partitioning of α-synuclein between random coil (in solution), α-helix (in association with membranes), and b-sheet in pathological aggregates).
Studies of folding and turnover of α-synuclein in cultured cells.
Analysis of the specificity of α-synuclein interactions with lipids, particularly long-chain polyunsaturated fatty acids, which catalyze irreversible oligomerization of the protein.
Representative Publications
George JM, and Yang M-L. 2005. "α-Synuclein physiology and membrane binding," in Molecular Mechanisms in Parkinson‘s Disease, Eds. Kahle, P. and Haass C., Landes Bioscience, in press.
Payton JE, Perrin RJ, Woods WS, and George JM. 2004. Structural determinants of PLD2 inhibition by α-synuclein. J. Mol. Biol. 337:1001-1009. [Abstract]
Perrin RJ, Payton JE, Barnett DH, Wraight CL, Woods WS, Ye L, and George JM. 2003. Epitope mapping and specificity of the anti-α-synuclein monoclonal antibody Syn-1 in mouse brain and cultured cell lines. Neurosci. Lett. 349:133-135. [Abstract]
George JM. 2002. The synucleins. Genome Biol. 3:REVIEWS 3002. [Abstract]
Payton JE, Perrin RJ, Clayton DF, and George JM. 2001. Protein-protein interactions of alpha-synuclein in brain homogenates and transfected cells. Mol. Brain. Res. 95:138-145. [Abstract]
Perrin RJ, Woods WS, Clayton DF, and George JM. 2001. Exposure to long chain polyunsaturated fatty acids triggers rapid multimerization of synucleins. J. Biol. Chem. 276:41958-41962. [Abstract]
Additional Information
View Publications by Julia M. George listed on the National Library of Medicine (PubMed)
Related Research (By Area):
Aging
Cell Signaling and Communication
Neurological and Psychiatric Conditions
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