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.

A reinvestment of $151,964 in a previous grant to WSU was made in 2015.  The previous award did not achieve complete elimination of the protein (colloquially but not accurately labeled “gluten”) that causes the autoimmune reaction in celiac disease patients.  The supplement will employ an additional genetic technique to eliminate the “gluten” and create wheat safe for celiac patients.  Complete elimination is necessary both for safety and for commercialization.

Richard Koenig replaced Sachin Rustgi as principal investigator in July 2016 due to Dr. Rustgi’s recruitment by Clemson University.

Celiac-safe Wheat

Grant Update

Principal Investigator:
Richard Koenig
Grantee Organization:
Washington State University
Grant Title:
Wheat for celiac patients and improved disease prevention
Grant Cohort and Year:
2015 Supplement (06)
Grant Period:
09/01/2015 - 08/31/2017 (Completed)
Grant Amount:
$151,964
In the previous granting cycle we obtained wheat genotypes stably expressing hairpin RNA and artificial micro (ami) RNAs. These small RNAs were specifically designed to target the wheat DEMETER gene, the major epigenetic regulator of prolamin accumulation in wheat endosperm. Wheat transformants were developed in the genetic background of soft white winter wheat cultivar Brundage 96. In a number of molecular, biochemical and immunological assays these transformants exhibited up to 75% reduction in amount of immunogenic prolamins. Preliminary baking tests performed on these reduced gluten wheat genotypes showed high gluten strength in comparison with other soft wheat genotypes and the untransformed control and baked into normal bread. Agronomical performance of the selected reduced-gluten wheat genotypes was also studied at the Cook Agronomy Farm. Expect for a few transformants the heading and anthesis dates of the transformants resembled that of the untransformed Brundage 96. In contrast most of transformants exhibited higher grain numbers and grain weights in comparison with the untransformed control. In order to achieve complete silencing of wheat DEMETER genes, we undertook an alternative approach for tissue specific suppression of DEMETER genes. For this purpose we attached a custom designed Xanthomons transcription activator like effector (TALE) to the universal Arabidopsis EAR-repression domain. To get the full benefit of the site-directed genome editing procedures this DME-specific TALE repressor is currently being introgressed in the wheat Dre2 (Derepressed for ribosomal protein S14 expression 2) genes with the help of a RNA guided Cas9 nuclease specifically designed to target the wheat Dre2 genes. The Dre2 enzyme was earlier reported to be responsible for activation of DEMETER apoenzyme to holoenzyme by installing iron-sulfur (Fe-S) cluster on it. The double-stranded breaks introduced in the wheat Dre2 genes will be repaired with the help of a donor plasmid carrying the DME-specific TALE repressor. The expected outcome of these targeted manipulations will be a wheat genotype showing silencing of wheat DME and Dre2 homoeologues. The major advantage of this approach is likely complete elimination of immunogenic prolamins from grains, as this strategy imposes regulation on DEMETER at transcriptional and post-translational levels.

Impact in Washington

Location of LSDF Grantee
Locations of Collaborations/Areas of Impact
Pullman

Legislative Districts:
9

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