CROPNUT: increasing iron in cereals
Lead Research Organisation:
King's College London
Department Name: Diabetes & Nutritional Sciences
Abstract
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Technical Summary
Most modern wheat varieties, although excellent providers of carbohydrates, are poor sources of mineral micronutrients. Levels of the micronutrients iron and zinc are especially low in the endosperm, which is used to make white flour. Conversely grains contain relatively high levels of the anti-nutrient phytate. Therefore, the Food Standards Agency requires all milled flour sold in the UK to be fortified with iron salts or iron powder. A much more sustainable method is biofortification, whereby plants are induced to translocate more minerals into edible parts. We have recently developed a high-iron wheat line by overexpressing a vacuolar iron transporter using an endosperm-specific promoter (Connorton et al, manuscript in preparation). The sequence are from wheat itself (cisgenic). Iron in the white flour fraction is increased 3-fold to 16 - 17 ppm, which would remove the legal requirement for fortification. However, we actually do not fully understand why this particular strategy is so successful whereas other strategies have only marginally increased iron and zinc levels. Here we propose to use the high-iron wheat line as a tool to understand how iron is transported into the grain and further distributed to the aleurone, endosperm and embryo. We will study changes in gene expression as a consequence of the increased iron flux, and map the route of iron through the different tissue and cell types using isotope studies and NanoSIMS imaging (with Dr Katie Moore, Manchester University). We will also investigate if the increased iron is due to increased uptake by the roots or increased remobilization from senescing leaves. In addition, we will investigate bioavailability of the iron for human nutrition in the white flour fractions and how this is affected by food processing, such as baking bread(with Paul Sharp, King's College London). This knowledge will be used to design non-GM approaches to increase the mineral content of cereals.
Planned Impact
The iron levels in the new high-iron wheat line are 16 - 17 mg/kg in white flour, well above the upper limit of natural variation (~ 12 mg/kg) and in line with the legal requirement for chemical fortification (16.5 mg/kg). So far, we do not see any negative impact on plant growth or yield. The work to date has been carried out in the Fielder cultivar, but this trait could now in principle be bred into modern commercial wheat varieties and remove the requirement for post-milling chemical fortification. We have contacted several potential UK stakeholders and received interested responses from the baking company Warburtons and Marks & Spencers (see letters of support).
One obstacle to more widespread acceptance is that the successful high-iron line, though not transgenic, is by definition genetically modified (GM). The approach taken was what is called cisgenic: we used a wheat promoter to change the timing and levels of expression of a wheat gene. So the sequences that were transformed are from the same species, The manipulations that are required cannot currently be achieved by non-GM methods. Although the cisgenic line is of interest to countries that do accept GM crops (e.g. India) most UK stake holders, and also the international maize and wheat improvement centre CIMMYT (see letter of support) are hesitant to use this line in their breeding programmes. We therefore seek to replicate the striking phenotype seen in this line through non-GM means.
Now that we know that a dramatic increase in iron and zinc in the endosperm of cereal grains is technically possible, it should be possible to design other, non-GM strategies to meet the same goal. For this we need to better understand what is changed in the high-iron line with regards to iron and zinc transport. We suspect that increased accumulation of iron into the vacuole of the endosperm has triggered other changes in gene expression, such as increased uptake by the roots and/or increased remobilization from senescing leaves, while lowering the saturation point of regulatory mechanisms. Though overexpressing genes in wheat through non-GM means is not currently feasible we do have a population of TILLING lines available with single nucleotide polymorphisms (SNPs) in potential genes of interest that will severely disrupt their function. These lines are not classed as GM and so through crossing with commercial wheat varieties high iron traits associated with these SNPs can be incorporated into existing breeding programmes. An alternative approach is CRISPR, which is also not classed as GM, and could be used to simultaneously knock down the function of multiple genes. The iron sensing and regulatory machinery of wheat would be excellent targets for these approaches.
One obstacle to more widespread acceptance is that the successful high-iron line, though not transgenic, is by definition genetically modified (GM). The approach taken was what is called cisgenic: we used a wheat promoter to change the timing and levels of expression of a wheat gene. So the sequences that were transformed are from the same species, The manipulations that are required cannot currently be achieved by non-GM methods. Although the cisgenic line is of interest to countries that do accept GM crops (e.g. India) most UK stake holders, and also the international maize and wheat improvement centre CIMMYT (see letter of support) are hesitant to use this line in their breeding programmes. We therefore seek to replicate the striking phenotype seen in this line through non-GM means.
Now that we know that a dramatic increase in iron and zinc in the endosperm of cereal grains is technically possible, it should be possible to design other, non-GM strategies to meet the same goal. For this we need to better understand what is changed in the high-iron line with regards to iron and zinc transport. We suspect that increased accumulation of iron into the vacuole of the endosperm has triggered other changes in gene expression, such as increased uptake by the roots and/or increased remobilization from senescing leaves, while lowering the saturation point of regulatory mechanisms. Though overexpressing genes in wheat through non-GM means is not currently feasible we do have a population of TILLING lines available with single nucleotide polymorphisms (SNPs) in potential genes of interest that will severely disrupt their function. These lines are not classed as GM and so through crossing with commercial wheat varieties high iron traits associated with these SNPs can be incorporated into existing breeding programmes. An alternative approach is CRISPR, which is also not classed as GM, and could be used to simultaneously knock down the function of multiple genes. The iron sensing and regulatory machinery of wheat would be excellent targets for these approaches.
Organisations
People |
ORCID iD |
Paul Sharp (Principal Investigator) |
Publications
Wan Y
(2022)
Localisation of iron and zinc in grain of biofortified wheat
in Journal of Cereal Science
Harrington SA
(2023)
A two-gene strategy increases iron and zinc concentrations in wheat flour, improving mineral bioaccessibility.
in Plant physiology
Balk J
(2019)
Improving wheat as a source of iron and zinc for global nutrition.
in Nutrition bulletin
Arafsha SM
(2023)
Strategies to increase the bioaccessibility and bioavailability of iron and zinc from cereal products.
in The Proceedings of the Nutrition Society
Description | The purpose of this award was to determine whether overexpression of a wheat iron transport (TaVIT2) which potentially controls the flow of iron between the aleurone cells and the starch endosperm (used to produce white flour) could increase the iron content of white flour. Most of the iron in wheat is contained within the aleurone cells which are removed along with the other bran components when wheat is milled to produce white flour. As a result, in the UK, white wheat flour is fortified to replace the iron lost during milling. Therefore if more endogenous wheat iron could be mobilised into the endosperm this might remove the requirement for fortification. We were provided with white flour from wheat plants over-expressing the TaVIT2 transporter. The iron content of the TaVIT2 flour was higher than that in control flour. Following in vitro digestion more iron was released from the TaVIT2 flour and more iron was taken up by human intestinal cells. This demonstrates that the higher levels of iron in the TaVIT2 flour is both bioaccessible and bioavailable. A further batch of flour was produced, this time from wheat plants over-expressing both TaVIT2 and the NAS gene, which produces the iron chelator nicotianamine. Iron levels in white flour were significantly higher than in control flour and in flour from TaVIT2-only wheat. The additional iron was again bioaccessible and bioavailable in in vitro digestion and cell uptake assays. These studies show that genetic transformation of wheat to express higher levels of a specific iron transporter and an iron chelator found in wheat increases the iron content of white flour and that this iron is available for absorption. Using flour from these transformed wheat plants could increase iron content of the diet and the amount of iron absorbed from cereal-based foods |
Exploitation Route | These data might inform government debate on the use of genetically modified plants for human consumption. Plant breeders, the agriculture sector and food manufacturers would be interested in these data as the use of these transformed wheat varieties might remove the need to fortify white wheat flour. |
Sectors | Agriculture Food and Drink Government Democracy and Justice |
Description | 'Raising the Pulse' (RtP): Systems analysis of the environmental, nutritional and health benefits of pulse-enhanced foods |
Amount | £2,027,639 (GBP) |
Funding ID | BB/W017946/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2022 |
End | 04/2025 |
Description | Biofortification with Zinc and Iron for Eliminating Deficiency in Pakistan (BiZIFED2) |
Amount | £1,676,210 (GBP) |
Funding ID | BB/S013989/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2019 |
End | 03/2022 |
Description | Improving the nutritional value and digestibility of rice to address double burden malnutrition in the Philippines and Thailand |
Amount | £1,012,374 (GBP) |
Funding ID | BB/T008873/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 02/2020 |
End | 02/2023 |
Description | MillNET_i: Millets and Nutritional Enhancement Traits for Iron bioavailability |
Amount | £1,623,623 (GBP) |
Funding ID | BB/S013954/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2019 |
End | 09/2021 |
Description | Presentation at Rank Prize Symposium, March 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Invited speaker at a small research symposium (30 invited attendees) focused on food processing and nutrition. Many of the delegates were early career researchers from UK and International HEI and industry. The symposium closed with a debate on future prospects for processing to increase nutritional value of foods. |
Year(s) Of Engagement Activity | 2019 |
Description | Presentation at the National Institute of Nutrition, India, Centenary Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited presentation on cereals as important nutritional sources of minerals as part of the NIN centenary conference " ALIGNING FOOD SYSTEMS FOR HEALTHY DIETS AND IMPROVED NUTRITION". The audience was diverse and included politicians, media, policymakers (e.g. from WHO and FAO) as well as international scientists from industry and academia. The invitation arose from an international collaboration with colleagues from NIN and has increased interest from other groups in India which might potentially lead to further collaborative research and submission of joint grant applications. |
Year(s) Of Engagement Activity | 2018 |
Description | Presentation on mineral bioavailability from cereals |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Plenary lecture at the Nutrition Society Winter Meeting on strategies to increase mineral bioavailability from cereals. This was an in-person conference with 200-300 attendees. Following the presentation there was a panel debate on the subject. |
Year(s) Of Engagement Activity | 2023 |
Description | Sigma Nutrition podcast |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Background to iron content of foods and iron metabolism aimed at a general audience. Questions were posed online and were responded to after the event. |
Year(s) Of Engagement Activity | 2022 |
Description | Webinar on food Structure and bioavailability |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | A presentation to the Institute of Food Science and Technology on food structure and how this can be manipulated to benefit mineral bioavailability. Questions were answered from the audience during the webinar. |
Year(s) Of Engagement Activity | 2023 |