Molecular chaperones are proteins that are activated by cellular stress and assist in preventing the aggregation of misfolded proteins. The small heat shock protein chaperone family (sHSPs) is a ubiquitous class of molecular chaperones that are heterogeneous in sequence, size, and substrate specificity but have a conserved function to bind partially denatured substrates and prevent their irreversible aggregation in an ATP-independent manner. The long term goals of my research are to elucidate the mechanism of sHSP chaperone action and to define the role of sHSPs in protection from oxidative stress. I will address the basic molecular mechanism of sHSP action during oxidative stress using a model organism, the cyanobacterium, Synechocystis PCC 6803. Synechocystis has only one sHSP, Hsp16.6, which has been shown to be required for the acquisition of thermotolerance. Importantly, my recent data demonstrate Hsp16.6 is also necessary for survival during oxidative stress. I will conduct biochemical studies in vitro using purified recombinant sHSPs to uncover mechanistic details of sHSP function and in parallel identify potential substrates protected by an sHSP during oxidative stress in vivo. Specifically I will 1) determine if there are conformational changes in Hsp16.6 induced by oxidative stress, 2) Determine if sHSPs can protect enzymes from irreversible oxidation and inactivation, and 3) Identify proteins that cooperate with Hsp16.6 during protection from oxidative stress. These fundamental studies will provide a better understanding of the role of sHSPs in cellular redox equilibrium and how sHSPs impact a vast spectrum of human diseases including neurodegenerative disorders, cardiovascular disease, and cancer. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM083588-01
Application #
7409233
Study Section
Special Emphasis Panel (ZRG1-F04B-T (20))
Program Officer
Haynes, Susan R
Project Start
2008-02-01
Project End
2009-06-30
Budget Start
2008-02-01
Budget End
2009-01-31
Support Year
1
Fiscal Year
2008
Total Cost
$51,278
Indirect Cost
Name
University of Arizona
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721