Award Abstract #0440799
Towards an Understanding of Protein Homeostasis in Cold-adapted Antarctic Fish

NSF Org:	ANT Antarctic Sciences Division
Initial Amendment Date:	April 26, 2005
Latest Amendment Date:	March 19, 2007
Award Number:	0440799
Award Instrument:	Continuing grant
Program Manager:	Roberta L. Marinelli ANT Antarctic Sciences Division OPP Office of Polar Programs
Start Date:	May 1, 2005
Expires:	April 30, 2009 (Estimated)
Awarded Amount to Date:	$535623
Investigator(s):	Gretchen Hofmann hofmann@lifesci.ucsb.edu (Principal Investigator)
Sponsor:	University of California-Santa Barbara Office of Research SANTA BARBARA, CA 93106 805/893-4188
NSF Program(s):	ANTARCTIC ORGANISMS & ECOSYST
Field Application(s):	0311000 Polar Programs-Related
Program Reference Code(s):	EGCH, 9232, 9169
Program Element Code(s):	5111

ABSTRACT

An unresolved question in the evolution of Antarctic fishes is how these organisms cope with cold-related protein damage and how the protein degradation machinery in Antarctic fish cells might be specially cold adapted to deal with elevated levels of protein misfolding at subzero temperatures. Investigators have found that the cold-adapted ectotherms are under unique selection pressures that may actually result in greater energetic costs of protein homeostasis rather than less. Given that the costs of protein synthesis are upwards of fifty percent in ectothermic organisms such as fish, exaggerated protein loss as a result of environmentally driven cold denaturation would have a significant impact on organismal performance. While cold denaturation of proteins and slow folding of proteins has been documented in some systems, very few studies have addressed how organisms in nature cope with extreme cold in terms of protein biogenesis. While the mechanism of cold denaturation is still not fully understood, temperatures at or near those encountered by Antarctic Notothenioids (icefish) have been shown to perturb protein structure (protein misfolding) for numerous proteins.

Thus, despite living at temperatures that are ecological norms for the species, polar seawater temperatures may nevertheless be "stressful" for Antarctic organisms in terms of maintaining protein homeostasis. In order to test this hypothesis, a more direct measure of levels of misfolded proteins is required. Specifically, by examining the role of a major pathway for the degradation of misfolded and damaged proteins, the ubiquitin-proteasome pathway, research plan to determine whether cells in Antarctic fish are over-loaded with damaged proteins, presumably because there is a high degree of protein misfolding and because perhaps the proteasome pathway is suppressed at cold temperatures. Ubiquitin (Ub) conjugates are common indicator of protein damage within a cell. Preliminary data suggest that despite the "slow and cold" lifestyle of the Antarctic species, the levels of ubiquitinated proteins were as high as those measured in at least one of the temperate New Zealand species.

The goals of this research are to: assess the relative amount of protein in Antarctic fish that has been tagged and targeted for degradation; to reveal whether Antarctic fish cells have elevated levels of protein degradation, as compared to New Zealand species, that could be related to extreme cold; to determine whether Antarctic cells are processing high levels of misfolded or other wise damaged proteins; and to examine how gene expression may have been altered in Antarctic fishes as an adaptation to near freezing temperatures. Broader impacts range from basic biology, through training of young scientists. Results from this study may highlight how Antarctic organisms may be models for studying cold denaturation of proteins in such as way as to benefit biomedical science.Additionally, these species may be models for studying cold denaturation of proteins in such as way as to benefit biomedical science.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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Hofmann, G.E. and S.D. Gaines.  "New tools to meet new challenges: Emerging technologies for managing marine ecosystems for resilience.,"  BioSciences,  v.58,  2008,  p. 42.

Hofmann, G.E. and S.P. Place.  "Genomics-enabled research in marine ecology: challenges, risks and pay-offs,"  Marine Ecology Progress Series,  v.332,  2007,  p. 249.

Todgham, A.E., E.A. Hoaglund, and G.E. Hofmann.  "Is cold the new hot?: Elevated ubiquitin conjugated protein levels in tissues of Antarctic fish as evidence for cold-denaturation of proteins in vivo.,"  Journal of Comparative Physiology B,  v.177,  2007,  p. 857.


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