Wheat for Celiac Patients and Improved Disease Prevention

Focus: 

To generate lysine-enriched wheat that is safe for individuals with celiac disease

Anticipated Impact: 

Improved health and quality of life of individuals with celiac disease and potential prevention of the disease in others

Abstract: 

The wheat varieties currently used to make flour for bread and pasta have two major limitations - 1. individuals with celiac disease cannot eat foods containing such flour; and 2. the grains are highly deficient in the essential amino acid lysine. This project seeks to develop new varieties of wheat that produce grain that celiac disease patients can safely consume. This will be accomplished by using molecular technologies to eliminate the proteins responsible for eliciting autoimmune reactions in people with celiac disease. Since the proteins to be removed have low lysine content, the resultant wheat will have higher lysine levels per unit weight. The investigators will assess dough formation and baking properties of the newly developed grains produced in collaboration with local growers. Development and commercialization of celiac-safe wheat is anticipated to have a large impact on the health and quality of life of individuals with celiac disease, and may help prevent induction of the disease in others by limiting their exposure to the immunogenic proteins.

See also:

Celiac-safe Wheat

Grant Update

Principal Investigator:
Diter vonWettstein
Grantee Organization:
Washington State University
Grant Title:
Wheat for Celiac Patients and Improved Disease Prevention
Grant Cohort and Year:
2009 Project Grant (01)
Grant Period:
03/08/2010 - 03/07/2015 (Completed)
Grant Amount:
$1,095,942
Collaborating Organizations:
Arcadia Biosciences, U.S. Department of Agriculture
We cloned wheat and barley DEMETER genes encoding 5-methyl cytosine DNA glycoslyase/lyase, responsible for transcriptional activation of immunogenic prolamins (including gliadins and low molecular weight glutenins) in the developing endosperm. The DEMETER genes were respectively assigned to the long arms of group 5 chromosomes (including 5AL, 5BL, and 5DL) in bread wheat, and chromosome arm 5HL in barley. To silence wheat DEMETER homoeologues a transgenic and a non-transgenic approach was followed. The former approach involves development of transgenic lines expressing DEMETER silencing artificial microRNAs (amiRNAs) and hairpin RNA (hpRNA). These small RNA species are uniquely capable of binding complementarily with DEMETER transcripts and thus silencing of corresponding genes by induction of cell’s inherent RNA interference machinery. The latter approach involves characterization of induced mutations in the active site of wheat DEMETER homoeologues. We have so far developed >400 transformants and identified 182 mutants in the active sites of wheat A, B and D subgenome DEMETER homoeologues. The 400 candidate transformants produced using biolistic and microspore electroporation based transformation approaches were analyzed for transgene integration(s) and its inheritance over generations. The transformants showing faithful inheritance of transgene were analyzed for transcriptional suppression of DEMETER homoeologues, and for accumulation of immunogenic prolamins. Analysis of the T2 grains revealed up to 76.4% reduction in the amount of immunogenic prolamins. Different T2s showed reduction in amount of different prolamin families. With the current transformation procedures there is no control on the site of transgene integrations and the number of copies integrated in the genome. Thus in view of multiple integrations and transgene zygosity at each integration site we are converting the best transformants with complementing prolamin profiles into doubled haploids so that these doubled haploids showing elimination of specific prolamins families will be crossed together to combine their effect in a single genotype. This will allow us to obtain wheat genotypes showing complete elimination of immunogenic prolamins. The preliminary test for the technological properties of the transformants suggested that the product quality of the transformants with significantly reduced amount of immunogenic prolamins, was not significantly modified and these genotypes can still be used to make cookies and bake breads. Further more, the selected transformants were propagated in field and four plant attributes (i.e., grain wt., grain no., heading and anthesis dates) that contribute to grain yield were recorded. The preliminary data suggested that most of the selected transformants resemble the untransformed control in their performance. In order get detailed information about the agronomical performance of the selected wheat genotypes we sequenced transcriptomes of these genotypes with controls. This analysis revealed many subtle differences between the transformants and controls especially in the endosperm development process, which has a major influence on grain yield. Moreover, to get deeper insight into the end-use quality of the selected genotypes a number of physical and biochemical characteristics were studied that reflect on the milling and baking quality of the selected gluten deficient transformants. But, more immunological assays and field data are required to make definitive conclusions.

Impact in Washington

Location of LSDF Grantee
Locations of Collaborations/Areas of Impact
Pullman
Seattle
Harrington
Hartline

Legislative Districts:
7, 9, 11, 12, 34, 36, 37, 43, 46

Health Impacts

Celiac-safe Wheat

Jun 19, 2015
SF Weekly
Jul 27, 2011
Wheat Life, Scott A. Yates
Mar 31, 2010
Northwest Science & Technology News
Jan 9, 2010
Food Safety Times