Research Interests:

New evidence suggests that mRNA localization prior to translation is a major mechanism for controlling virtually all aspects of cellular structure and function (Lecuyer et al., 2007). How are mRNAs transported to sites of local translation? What key factors are involved in translational repression during transport? What local signals are required to relieve this repression? Using a variety of model systems, it has been established that mRNAs are regulated by sequence motifs within specific mRNAs acting in concert with RNA binding proteins and microRNAs (miRNAs). Furthermore, it is now widely accepted that these processes require the formation and function of larger, highly conserved, ribonucleoprotein (RNP) particles. While much progress has been made, what remains unknown is precisely how most mRNAs are locally controlled by these RNP- and miRNA-mediated regulatory pathways.

My research examines the molecular and cellular mechanisms underlying temporal and spatial mRNA regulation using the fruit fly Drosophila melanogaster as a model system. My lab is currently focusing on two mechanistically related problems. My primary research project explores functions for neuronal RNPs ("neuronal granules") and miRNAs in the regulation of local mRNA translation and synaptic plasticity. Together, components of these particles determine whether synapse-localized mRNAs are transported to a specific location (e.g. the synapse), locally translated, or targeted for storage and/or degradation. I am particularly interested in the development of fluorescent reporters to study these processes in real-time within living neurons. My secondary research project investigates functions for local, co-translational, mRNA decay in the regulation of plasticity processes. Techniques used in my lab include confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), immunohistochemistry, biochemistry, molecular biology, and molecular genetics.

The rationale behind this work is based on a significant body of evidence indicating that mRNA regulatory mechanisms are highly conserved across phyla. Therefore, by gaining an understanding of these processes in Drosophila, we will be better capable of developing testing and/or treatments for common problems in humans associated with defects in synaptic plasticity (e.g. dementia, Alzheimer’s disease, mental retardation, addiction, mental disease).

Link to Barbee Publication List

Recent Publications:

• Kwak JE, Drier E, Barbee SA, Ramaswami M, Yin JCP, Wickens M. (2008) GLD2 poly(A) polymerase is required for long-term memory. Proc. Natl. Acad. Sci. U.S.A. 105(38):14644-14649. (DOI: 10.1073/pnas.0803185105)
• Satterlee J, Barbee S, Jin P, Krichevsky A, Salama S, Schratt G, and D-Y. (2007) Non-coding RNAs in the brain. J Neurosci. 27(44):11856-11859. (DOI: 10.1523/JNEUROSCI.3624-07.2007)
• Hillebrand J*, Barbee SA*, and M. Ramaswami. (2007) P-body components, microRNA regulation, and synaptic plasticity. ScientificWorldJournal. 7:178-190. * Co-first authors.
• Barbee SA, Estes PS, Cziko A-M, Hillebrand J, Luedeman RA, Coller JM, Johnson N, Howlett IC, Geng C, Ueda R, Brand AH, Newbury SF, Wilhelm JE, Levine RB, Nakamura A, Parker R, and M. Ramaswami. (2006) Staufen- and FMRP-containing neuronal RNPs are structurally and functionally related to somatic P-bodies. Neuron 52(6):997-1009. (DOI: 10.1016/j.neuron.2006.10.028)
• Barbee SA, and T.C. Evans. (2006) The Sm proteins regulate germ cell specification during early C. elegans embryogenesis. Dev. Biol. 291(1):132-143. (DOI: 10.1016/j.ydbio.2005.12.011)
• Barbee SA, Lublin AL, and T.C. Evans. (2002) A novel function for the Sm proteins in germ granule localization during C. elegans embryogenesis. Curr Biol. 12(17):1502-1506. (DOI: 10.1016/S0960-9822(02)01111-9)