Project Summary:

Hi, I’m Lane, and I am a graduate student in the Broadie lab! My project focuses on Fragile X Syndrome. Fragile X Syndrome (FraX), caused by a mutation in a single gene (FMR1) is the most common inherited mental retardation disease with a prevalence of 1 in 4000 males and 1 in 8000 females. FraX accounts for about 50% of X-linked mental retardation. FraX patients display hyperactivity, attention deficit, obsessive-compulsive behavior, and aggression. Clinically, these symptoms indicate disruption of multiple neurotransmitter systems, including both cholinergic and glutamatergic. Available treatments inadequately target only a subset of these symptoms, so there is a need for research into the genetic and neurobiological basis of this disease.

In my work, I am performing systematic in vivo structure-function analyses of the human FMR genes in the Drosophila FraX model. Conservation between dFMRP and the three human proteins (FMRP, FXR1P, FXR2P) will be assayed by introducing each into dfmr1 null mutants and testing rescue of neurological phenotypes, such as dendritic morphology. Next, deletion mutations will be engineered to test the in vivo requirements of each conserved protein domain: nuclear localization and export signals, RNA-binding K-Homology 1 and 2 domains, and the RGG box. Behavioral assays will test complex movement, circadian activity patterns, and olfactory associative memory. Cellular assays on neuronal architecture and synaptic mechanisms will be done in brain mushroom body, neuromuscular junction, and primary neuronal culture.

Education:

Publications:

1. Adams, DG; Coffee, Jr., RL; Zhang, H; Pelech, S; Strack, S; Wadzinski, BE. Positive Regulation of Raf1-MEK1/2-ERK1/2 Signaling By Protein Serine/Threonine Phosphatase 2A Holoenzymes, J. Biol. Chem. 2005; 280(52): 42644-42654.

2. Arya, DP; Coffee, Jr., RL; Xue, L. From Triplex to B-form Duplex Stabilization: Reversal of Target Selectivity by Aminoglycoside Dimers. Bioorg. Med. Chem. Lett. 2004; 14(18): 4643-4646.

3. Davis, WC; Venzie, JL; Willis, B; Coffee, Jr., RL; Arya, DP; Marcus, KR. Particle Beam Glow Discharge Mass Spectrometry: Spectral Characteristics of Nucleobases. Rapid Commun. Mass Spectrom. 2003; 17: 1749-1758.

4. Arya, DP; Micovic, L; Charles, I; Coffee, Jr., RL; Willis, B; Xue, L. Neomycin Binding to Watson-Hoogsteen (W-H) DNA Triplex Groove: A Model. J. Am. Chem. Soc. 2003; 125(13): 3733-3744.

5. Arya, DP; Coffee, Jr., RL; Charles, I. Neomycin-Induced Hybrid Triplex Formation. J. Am. Chem. Soc. 2001; 123(44): 11093-11094.

6. Arya, DP; Coffee, Jr., RL; Willis, B; Abramovitch, AI. Aminoglycoside—Nucleic Acid Interactions: Remarkable Stabilization of DNA and RNA Triple Helices by Neomycin. J. Am. Chem. Soc. 2001; 123(23): 5385-5395.

7. Arya, DP; Coffee, Jr., RL. DNA Triple Helix Stabilization by Aminoglycoside Antibiotics. Bioorg. Med. Chem. Lett. 2000; 10: 1897-1899.

8. Westphal, RS; Coffee, Jr., RL; Marotta, A; Pelech, SL; Wadzinski, BE. Identification of Kinase-Phosphatase Signaling Modules Composed of p70 S6 Kinase-Protein Phosphatase 2A (PP2A) and p21-activated Kinase-PP2A. J. Biol. Chem. 1999; 274(2): 687-692.