by applicant): Ricin and Shiga toxin are among the most potent poisons known. They are able to kill mammalian cells by catalytically inactivating ribosomes. This entails binding to cell surface receptors, endocytic uptake, and intracellular trafficking to reach a compartment.from which the catalytic fragment translocates into the cytosol where its substrate is located. Because of this, they pose a serious threat to human health, a threat recently extended by their potential use as agents for bioterrorism. At the moment, no effective inhibitors or vaccines are available to combat this danger. The proposed program is a combination of four complementary research projects aimed at overcoming these limitations: a) Developing vaccines. Current vaccination approaches may be limited in the case of ricin because they involve modification of the active

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI065869-03
Application #
7176156
Study Section
Special Emphasis Panel (ZAI1-GB-M (M1))
Program Officer
Schmitt, Clare K
Project Start
2005-02-01
Project End
2010-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
3
Fiscal Year
2007
Total Cost
$116,233
Indirect Cost
Name
University of Warwick
Department
Type
DUNS #
227821915
City
Coventry
State
Country
United Kingdom
Zip Code
CV4 8-UW
Aletrari, Mina-Olga; McKibbin, Craig; Williams, Helen et al. (2011) Eeyarestatin 1 interferes with both retrograde and anterograde intracellular trafficking pathways. PLoS One 6:e22713
Pawar, Vidya; De, Antara; Briggs, Laura et al. (2011) RNAi screening of Drosophila (Sophophora) melanogaster S2 cells for ricin sensitivity and resistance. J Biomol Screen 16:436-42
Li, Shuyu; Spooner, Robert A; Allen, Stuart C H et al. (2010) Folding-competent and folding-defective forms of ricin A chain have different fates after retrotranslocation from the endoplasmic reticulum. Mol Biol Cell 21:2543-54
Crispin, Max; Chang, Veronica T; Harvey, David J et al. (2009) A human embryonic kidney 293T cell line mutated at the Golgi alpha-mannosidase II locus. J Biol Chem 284:21684-95
Spooner, Robert A; Hart, Philip J; Cook, Jonathan P et al. (2008) Cytosolic chaperones influence the fate of a toxin dislocated from the endoplasmic reticulum. Proc Natl Acad Sci U S A 105:17408-13
Watson, Peter; Spooner, Robert A (2006) Toxin entry and trafficking in mammalian cells. Adv Drug Deliv Rev 58:1581-96