[Neuropostdocs] Fwd: postdoc available -- UCSD, circadian rhythms

[Samuel Beshers]

On 9/27/2010 12:27 PM, Martha Gillette wrote:
>
>
> -------- Original Message --------
> Subject: 	postdoc available
> Date: 	Mon, 27 Sep 2010 09:47:11 -0700
> From: 	David K. Welsh <welshdk at ucsd.edu>
> To: 	Martha Gillette <mgillett at illinois.edu>
>
>
>
> *Project Title: Circadian Clock Cells: Autonomy, Persistence, and 
> Calcium Dependence*
> *ABSTRACT*
> Daily oscillations in mammalian physiology and behavior persist even 
> in a constant environment, and their disruption leads to jet lag, 
> sleep disorders, and other maladies. Such "circadian" (ca. 24 hr) 
> rhythms depend on a biological clock located within the brain, in the 
> suprachiasmatic nucleus (SCN). Most cells express "clock genes", 
> components of a transcriptional feedback loop comprising the 
> intracellular clock, but the SCN is the master pacemaker that 
> synchronizes cellular oscillators in tissues throughout the body.* 
> Objective:* The goal of this project is to explore the interdependence 
> of circadian transcriptional, electrical, and calcium rhythms in 
> individual SCN neurons and fibroblasts. Specifically, we propose to 
> determine whether calcium rhythms exist in non-SCN cells such as 
> fibroblasts, and whether calcium rhythms (as opposed to a permissive, 
> tonic level of calcium) are required for clock gene and electrical 
> activity rhythms in SCN neurons.* Methodology:* This will be 
> accomplished by using bioluminescent probes to image clock gene 
> transcription rhythms, multelectrode arrays to monitor neuronal firing 
> rhythms, and genetically encoded fluorescent probes to image calcium 
> rhythms. We will then test causal relationships among these circadian 
> rhythms, blocking the transcription loop using cells deficient for the 
> core clock gene/ Bmal1-/-/, blocking the neuronal firing rhythm with 
> tetrodotoxin, and clamping calcium to various levels by transfecting 
> the gene for the calcium buffer parvalbumin.* Findings:* So far, we 
> have succeeded in culturing SCN neurons in slice and dispersed cell 
> preparations, monitoring/ Per2/ clock gene expression rhythms in 
> individual fibroblasts and SCN neurons by bioluminescence imaging, and 
> monitoring neuronal firing in individual SCN neurons using 
> multielectrode arrays. We are now focusing on integrating these two 
> methods with calcium imaging. We are characterizing our "Cameleon" 
> mouse, which we have found expresses the NSE-YC2.1 calcium reporter in 
> dispersed SCN neurons. We are also evaluating several highly sensitive 
> new fluorescent probes obtained from other groups. Finally, with the 
> help of a computer science student, we are beginning to develop 
> software facilitating real-time comparison of imaging and 
> electrophysiology data.* Clinical Significance:* Circadian clock 
> dysfunction is the primary cause of some sleep disorders, and has 
> recently been implicated in the pathophysiology of cancer, diabetes, 
> and bipolar disorder. These studies will lead to an improved 
> understanding of fundamental circadian clock mechanisms and circadian 
> disorders, and serve as a basis for novel therapeutic approaches.
>
> -- 
>    
>
> David K. Welsh, M.D., Ph.D.
> Department of Psychiatry
> University of California, San Diego
> 9500 Gilman Drive #0603
> La Jolla, CA 92093-0603
>
> office: BSB 2084
> phone: (858) 246-0894
> email: welshdk at ucsd.edu
> web: http://circadian.ucsd.edu

-- 
Samuel Beshers, Ph.D.
Neuroscience Program Coordinator
Research Associate, Department of Entomology
318B Morrill Hall
505 South Goodwin Ave
Urbana, IL  61801
217-333-4971
217-244-3499 fax

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