The Bacillus thuringiensis Cry proteins are novel bacterial toxins with practical application as biological insecticides for the targeting of specific crop pests (caterpillars, beetles, nematodes) and disease vectors (mosquitoes). Insect ingestion of B. thuringiensis crystals [or spores and crystals] leads to solublization and proteolytic processing of Cry proteins that are thought to oligomerize and then insert into the midgut cells of insect. In the leading model for mechanism of action, this insertion results in the formation of cation-specific ion channels that collapse the electrochemical gradient of the midgut cells and ultimately leads to insect death. One important step towards understanding how Cry proteins insert into membranes would be the availability of Cry protein structures in both their soluble and membrane-inserted forms. Crystallographic efforts have provided structures of several Cry protein variants in their soluble forms, but as yet no structure of a Cry protein in its membrane inserted-form has been determined. This R21 grant will explore strategies towards the structural determination of such a membrane-inserted Cry toxin.

Public Health Relevance

The Bacillus thuringiensis Cry proteins are novel bacterial toxins with practical application as biological insecticides for the specific targeting of insect crop pests and disease vectors. This proposal seeks to determine the structure of Cry toxins in the form that kills insects, knowledge that could be used to generate improved toxins. Such super Cry toxins could be used to improve human health by increasing crop yields, thereby helping to reduce human malnutrition, and by killing mosquitoes that can transmit diseases, resulting in lower incidence of sickness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI081291-02
Application #
7751274
Study Section
Biochemistry and Biophysics of Membranes Study Section (BBM)
Program Officer
Costero, Adriana
Project Start
2008-12-19
Project End
2011-11-30
Budget Start
2009-12-01
Budget End
2011-11-30
Support Year
2
Fiscal Year
2010
Total Cost
$148,500
Indirect Cost
Name
Ohio State University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Nair, Manoj S; Lee, Marianne M; Bonnegarde-Bernard, Astrid et al. (2015) Cry protein crystals: a novel platform for protein delivery. PLoS One 10:e0127669