JOSEPH BESHARSE

..Proper morphogenesis of photoreceptor neurons is essential for their normal function and survival. We have characterized a zebrafish mutation, cannonball, that completely disrupts photoreceptor morphogenesis...

..The goal of this study was to determine the temporal pattern of nocturnin mRNA expression in multiple tissues of the mouse...

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..Furthermore, semithin sections can be used to locate GFP-expressing cells for examination by immunoelectron microscopy of the same material after thin sectioning...

..Our data indicate that all four mammalian IFT proteins are part of a highly conserved complex in multiple ciliated cell types. Furthermore, IFT20 appears to bridge kinesin II with the IFT complex...

..In contrast, dominant-negative KIF17 has no obvious effect on inner segment or synaptic organization but has an immediate impact on outer segment assembly...

..Those features illustrate how further analysis of photoreceptor IFT may provide insight into both IFT cargo and the role of alternative IFT kinesins...

..Our analysis shows that Kif17 is essential for photoreceptor OS development, and suggests that Kif17 plays a cell type specific role in vertebrate ciliogenesis...

..IFT52-GFP and IFT57-GFP mimicked this pattern in transgenic Xenopus...

..We further find that mice with a mutation in the IFT particle protein gene, Tg737/IFT88, have abnormal OS development and retinal degeneration. Thus, IFT is important for assembly and maintenance of the vertebrate OS...

..It also identifies 18 new genes that should be investigated for a role in circadian rhythms in peripheral tissues...

..Finally, the interactions between the retinal clock(s) and the master clock in the SCN are examined...

..Our data support a pivotal role for Nocturnin downstream of the circadian clockwork in the posttranscriptional regulation of genes necessary for nutrient uptake, metabolism, and storage...

..Arrestin-EGFP mass was conserved during a large-scale, light-driven redistribution in which approximately 40% of the protein in the inner segment moved to the outer segment in less than 30 minutes...

..These data support a specific role for dynein 2 in the generation and maintenance of cilia...

..NOC may act in turning off the expression of genes that are required to be silenced as a response to these extracellular signals...

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..The goal of this research project is to determine the mechanism of targeting of a protein (membrane guanylyl cyclase) that when disrupted genetically leads to severe photoreceptor degeneration and blindness. ..

..They will also attend and present papers at National meetings. ..

..This project fills specific gaps in our knowledge of retinal circadian organization at the cellular level in a mammalian system, and assesses the potential effects of circadian gene disruption on retinal health. ..

..The funding requested in this application will be used to support travel and conference expenses for pre- and post-doctoral trainees, and entry level scientists that have not yet established their own research programs. ..

..The goal of this research project is to determine the mechanism of targeting of a protein (membrane guanylyl cyclase) that when disrupted genetically leads to severe photoreceptor degeneration and blindness. ..

..Disruption of these interactions in constant light is proposed to account for disruption of circadian rhythms and for known alterations in photoreceptor membrane turnover. ..

..Specific Aim 3. To characterize kinesin-like proteins in photoreceptor ciliary axonemes with emphasis on their location and potential role as a transport motor. ..

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..After the project period, the long term care of the instrument for use of NIH funded investigators will be placed under the supervision of the existing imaging core facility. ..