Investigating genes involved in leucine amino acid synthesis in pearl millet for designing crop products providing better control to type-2 diabetes.

Diabetes is a massive global issue and products designed to control glycemic response in vulnerable populations have a very wide potential impact globally. There were 347 million diabetes sufferers worldwide in 2011; China alone has 90 million diabetics and India 30 million with the European region currently at 60 million. The World Health Organisation (WHO) estimated that, worldwide, 3.4 million people died due to high blood glucose in 2004 and that this figure is set to double by 2030.

Compared to other cereals, pearl millet contains high levels of leucine amino acid which stimulates insulin secretion via down-regulation of surface expression of adrenergic alpha 2A receptor through the mTOR pathways (Leucine secretion pathway). Such characteristics make pearl millet as a favoured grain in managing insulin resistance and cardiovascular diseases in type 2 diabetes. This project will make use of genetic resources of pearl millet available in PI’s laboratory, in conjunction of genomics and metabolomics platforms available within IBERS, in understanding the basis and extent of genetic variations for leucine amino acid present in pearl millet gene pool. A pearl millet inbred germplasm association panel (PMiGAP), representing global genetic variation present in world collection of pearl millet germplasm, is planned to be utilised in this study. Briefly, PMiGAP entries will be re-sequenced using genotype-by-sequencing (GBS) approaches, phenotyped for leucine amino acid and mTOR pathways, and genotype-phenotype associations identified using genome wide association studies (GWAS). Chemical biomarkers will also be generated on individual genotypes of the PMiGAP using ultra-high accurate mass Liquid Chromatography Mass Spectrometry (LC-MS) using Orbitrap technology in combination with Machine Learning data analysis methods (such as Random Forest). Candidate biomarkers found to be associated with leucine biosynthesis and other linked biochemical pathways will then be quantified and validated by targeted LC-MS using Triple Quad technology.

Research in the areas of pearl millet grain nutrition, starch components, and their roles in the control of type-2 diabetes are actively pursued in RY’s lab through the BBSRC, Unilever, and Innovate UK’s agritech catalyst financed grants and will complement both the proposed project and the existing one.

A major output of the PhD study will be in elucidating both the biological basis of such variations and how such variations can be used in improving grain characteristics of pearl millet and other staple crops in better control of type-2 diabetes.

The project will offer a very strong training element to the student in multiple areas of biology and emerging technologies (genetics, genomics, metabolomics, marker assisted breeding) and general areas of plant biology in relation to an important and growing health concern. The project will offer ample opportunities for the student to develop their own areas and high impact factor publications out of the work

This project will expose the student to the facilities and interdisciplinary skill-base at IBERS. As a member of the “Abiotic Stress Resistance and Nutrient-Use-Efficiency” and the “Public Good Plant Breeding” groups the student will be trained in bioinformatics, molecular biology, genomics, metabolomics, and post genomic analyses as appropriate. The student will have opportunities to contribute to a larger research project and will benefit from access to data sets generated by the RY group.