The applicant's goal is to obtain a position as Assistant Professor at an academic institution. The conventional route to this goal has been thwarted by childbirth, followed by a debilitating series of treatments for cancer. The proposed project provides a strong component of new training for the study of a zebrafish motility mutant, shocked, which compliments and extends skills acquired from graduate student and post-doctoral training. Over one hundred zebrafish mutations exist that affect the ability of a young fish to swim. Several of these mutations have already proved relevant to human myasthenic syndromes. The shocked mutation is unusual in that the motility defect improves with age. Shocked fish are initially paralyzed but acquire the ability to swim over the course of several days. Preliminary data suggests that excessive electrical coupling underlies the defective swimming phenotype in shocked fish. Although the vertebrate neuromuscular junction is the best studied of any synapse and electrical coupling is a feature of all immature vertebrate muscle, the significance of electrical coupling among muscle cells has not been addressed. The proposed research includes three aims: 1) To pursue the functional consequences of gap junctions for muscle synaptic physiology in wild type and shocked fish; 2) to identify the gene that underlies the shocked phenotype by parallel approaches of positional cloning and sequencing likely candidates; and 3) to understand the mechanisms that underlie the initial paralysis in shocked fish as well as their subsequent recovery. This work will be carried out in the laboratory of Dr. Paul Brehm, an expert in development of the vertebrate neuromuscular synapse and ion channel function. More recently his laboratory has focused on analyzing zebrafish motility mutants and has made great progress in a short time, discovering the molecular basis for several motility mutants including sofa potato (acetylcholine receptor delta subunit), relaxed (dihydropyridine receptor), and twitch once (rapsyn). Moreover, these studies have yielded new insight into the roles of the receptor and rapsyn in structuring the synapse. Dr. Paul Brehm's laboratory is part of a tight knit group of five independent researchers with distinct but related interests and shared microscopy and molecular facilities that create an environment with ample resources to carry out the proposed research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01NS048200-03
Application #
7052835
Study Section
NST-2 Subcommittee (NST)
Program Officer
Porter, John D
Project Start
2004-05-01
Project End
2008-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
3
Fiscal Year
2006
Total Cost
$124,378
Indirect Cost
Name
State University New York Stony Brook
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
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Ganser, Lisa R; Dallman, Julia E (2009) Glycinergic synapse development, plasticity, and homeostasis in zebrafish. Front Mol Neurosci 2:30
Mongeon, Rebecca; Gleason, Michelle R; Masino, Mark A et al. (2008) Synaptic homeostasis in a zebrafish glial glycine transporter mutant. J Neurophysiol 100:1716-23