Salamanders are important vertebrate model organisms in biomedical research. The Salamander Genome Project (SGP) is developing, applying, and making available genomic and bioinformatics resources for salamanders and in particular the Mexican axoloti (Ambystoma mexicanum). This renewal application proposes two objectives to further enhance axoloti genome resources. First, a 3x Bacterial Artificial Chromosome (BAC) library will be created and screened to identify clones that contain axoloti genes of interest. This list of clones will be made available via the SGP website (Sal-Site) and 25 BACs will be prioritized by the community for isolation and sequencing. A second objective will innovate an approach to sequence the large axoloti genome. Whole axoloti chromosomes that correspond to the third largest chromosome (Chr3) in the karyotype will be isolated by laser capture microscopy. DNA fragment libraries will be generated from the captured chromosomes and these will be sequenced to yield a Chr3 draft assembly, whose contiguity and conceptual context will be increased by integrating paired-end sequences from fosmids, protein-coding sequences deriving from expressed sequence tags, and markers defining linkage group 3 of the Ambystoma meiotic map. Accomplishment of these objectives will yield resources to enable functional studies of genes and epigenetic mechanisms. Also, the project will innovate a 'one-chromosome-at- a time'approach to sequence the large axoloti genome. As a final objective of the application, a historically significant collection of axolotis in the Ambystoma Genetic Stock Center (AGSC) will be maintained and distributed to NIH-funded researchers. Since 1969, the AGSC axoloti collection has been supported by funds received from the National Science Foundation. An increasing number of NIH researchers are requesting axoloti living stocks for regeneration research and at the same time, there is need to develop a stable, long term funding model to maintain this irreplaceable resource. A dual NIH-NSF funding model is proposed where costs associated with the maintenance and distribution of axoloti stocks will be split equally between the NSF and NIH.

Public Health Relevance

(provided by applicant): Fundamental genome and living stock resources are needed for salamanders so that biomedical researchers can translate biological information to humans. In particular, salamanders are primary vertebrate models for organ regeneration, tissue repair, and post-embryonic development.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Resource-Related Research Projects (R24)
Project #
9R24OD010435-12
Application #
8268090
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Program Officer
O'Neill, Raymond R
Project Start
2001-10-01
Project End
2016-06-30
Budget Start
2012-07-23
Budget End
2013-06-30
Support Year
12
Fiscal Year
2012
Total Cost
$317,970
Indirect Cost
$97,970
Name
University of Kentucky
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Amamoto, Ryoji; Huerta, Violeta Gisselle Lopez; Takahashi, Emi et al. (2016) Adult axolotls can regenerate original neuronal diversity in response to brain injury. Elife 5:
Keinath, Melissa C; Voss, S Randal; Tsonis, Panagiotis A et al. (2016) A linkage map for the Newt Notophthalmus viridescens: Insights in vertebrate genome and chromosome evolution. Dev Biol :
Ponomareva, Larissa V; Athippozhy, Antony; Thorson, Jon S et al. (2015) Using Ambystoma mexicanum (Mexican axolotl) embryos, chemical genetics, and microarray analysis to identify signaling pathways associated with tissue regeneration. Comp Biochem Physiol C Toxicol Pharmacol 178:128-35
Farkas, Johanna E; Monaghan, James R (2015) Housing and maintenance of Ambystoma mexicanum, the Mexican axolotl. Methods Mol Biol 1290:27-46
Voss, S Randal; Palumbo, Alex; Nagarajan, Radha et al. (2015) Gene expression during the first 28 days of axolotl limb regeneration I: Experimental design and global analysis of gene expression. Regeneration (Oxf) 2:120-136
Sommer, Lauren M; Cho, Hyuk; Choudhary, Madhusudan et al. (2015) Evolutionary Analysis of the B56 Gene Family of PP2A Regulatory Subunits. Int J Mol Sci 16:10134-57
Keinath, Melissa C; Timoshevskiy, Vladimir A; Timoshevskaya, Nataliya Y et al. (2015) Initial characterization of the large genome of the salamander Ambystoma mexicanum using shotgun and laser capture chromosome sequencing. Sci Rep 5:16413
McCusker, Catherine D; Athippozhy, Antony; Diaz-Castillo, Carlos et al. (2015) Positional plasticity in regenerating Amybstoma mexicanum limbs is associated with cell proliferation and pathways of cellular differentiation. BMC Dev Biol 15:45
Athippozhy, Antony; Lehrberg, Jeffrey; Monaghan, James R et al. (2014) Characterization of in vitro transcriptional responses of dorsal root ganglia cultured in the presence and absence of blastema cells from regenerating salamander limbs. Regeneration (Oxf) 1:1-10
Thompson, Sierra; Muzinic, Laura; Muzinic, Christopher et al. (2014) Probability of Regenerating a Normal Limb After Bite Injury in the Mexican Axolotl (Ambystoma mexicanum). Regeneration (Oxf) 1:27-32

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