In a post-genomic era, systems analyses have revealed interconnected networks between gene products. Such networks predict the relationship between interacting proteins and group proteins into clusters to facilitate definition of protein function. Understanding networks of protein-protein interactions in the brain will undoubtedly lead to a better understanding of neurological diseases and identify new targets for therapeutic agents. Several large scale projects have used high throughput yeast two hybrid (Y2H) analyses to identify interacting products of open reading frames (ORES) of an organism. Functionally important protein interaction networks were defined and, for C elegans, it was shown that essential proteins often interact with one another ^^?^^. Similar analyses are useful for discovering common mechanisms of disorders of CNS development as illustrated by a recent study that examined a protein interaction network of cerebellar ataxias by Y2H and networking analyses ^^. The power of the Y2H approach in elucidating pathogenic mechanisms of neurodegenerative disorders is remarkable. Many human neurodegenerative, developmental, and cognitive function disorders have been associated with multiple alleles. Multiple genes or genetic loci have also been implicated in complex disorders such as autism ^?. Linkage analysis suggests that many genetic loci are associated with autism and it is conceivable that the genes associated with autism could interconnect, having effects on similar cellular pathways (13-14,19). In addition, studies of diseases associated with a single gene have also benefited from studies of protein interactions. It is estimated that -80% of disease-associated SNPs destabilize a protein's structure and thereby may alter interactions with other proteins (2,38,41). Efforts to understand how protein interactions mediate complex biological processes are maior components of the research goals of NINDS supported investigators at UAB. Core C will facilitate progress in these areas. We propose to maintain a Protein Interaction Core that offers expression of proteins in both prokaryotic and eukaryotic expression systems suitable for protein purification in-vitro and expression in-vivo, vector design and selection for in-vitro and in-vivo expression, biochemical and imaging characterization of protein interactions including FRET and split luciferase/GFP, yeast two-hybrid screening systems and generation of constructs for tandem affinity purification (TAP) and mass spectroscopy. The goal of the Core Laboratory is to accelerate identification and characterization of biologically important protein interactions without the need to establish these methodologies in individual NINDS supported laboratories. The Core Laboratory personnel will assist investigators in selection of appropriate screening systems, generate expression vector constructs for screening assays, and provide troubleshooting and technical assistance in the screening procedures. The Core Laboratory will also facilitate the exchange of reagents and more importantly, expand an information and reagent sharing resource ( ) that will permit individual laboratories to share relevant experience with protein expression systems and interacting protein screening systems with other NINDS supported investigators at UAB. Finally, the core laboratory will limit redundancy in development of these methodologies and permit more efficient use of the resources provided by NINDS to investigate protein function in complex biologic systems that are the focus of study by NINDS supported investigators at UAB. Table 1 provides several examples of the interaction of the Protein Interaction Core Core C) with NINDS supported UAB investigators.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Center Core Grants (P30)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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University of Alabama Birmingham
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Adlaf, Elena W; Vaden, Ryan J; Niver, Anastasia J et al. (2017) Adult-born neurons modify excitatory synaptic transmission to existing neurons. Elife 6:
Killion, Christy H; Mitchell, Elizabeth H; Duke, Corey G et al. (2017) Mechanical loading regulates organization of the actin cytoskeleton and column formation in postnatal growth plate. Mol Biol Cell 28:1862-1870
Boyd, Nathaniel H; Walker, Kiera; Fried, Joshua et al. (2017) Addition of carbonic anhydrase 9 inhibitor SLC-0111 to temozolomide treatment delays glioblastoma growth in vivo. JCI Insight 2:
Van Beusecum, J P; Zhang, S; Cook, A K et al. (2017) Acute toll-like receptor 4 activation impairs rat renal microvascular autoregulatory behaviour. Acta Physiol (Oxf) 221:204-220
van Groen, Thomas; Schemmert, Sarah; Brener, Oleksandr et al. (2017) The A? oligomer eliminating D-enantiomeric peptide RD2 improves cognition without changing plaque pathology. Sci Rep 7:16275
Oliveira-Souza, Fred G; DeRamus, Marci L; van Groen, Thomas et al. (2017) Retinal changes in the Tg-SwDI mouse model of Alzheimer's disease. Neuroscience 354:43-53
Evonuk, Kirsten S; Prabhu, Sumanth D; Young, Martin E et al. (2017) Myocardial ischemia/reperfusion impairs neurogenesis and hippocampal-dependent learning and memory. Brain Behav Immun 61:266-273
Cohen, Joshua L; Jackson, Nateka L; Ballestas, Mary E et al. (2017) Amygdalar expression of the microRNA miR-101a and its target Ezh2 contribute to rodent anxiety-like behaviour. Eur J Neurosci 46:2241-2252
Patterson, Kelsey C; Hawkins, Virginia E; Arps, Kara M et al. (2016) MeCP2 deficiency results in robust Rett-like behavioural and motor deficits in male and female rats. Hum Mol Genet 25:5514-5515
Brady, Lillian J; Bartley, Aundrea F; Li, Qin et al. (2016) Transcriptional dysregulation causes altered modulation of inhibition by haloperidol. Neuropharmacology 111:304-313

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