Wheat (Triticum aestivum) is one of the major sources of food in the world. Production of wheat is under threat due to the migratory, root-lesion nematode Pratylenchus thornei, particularly in the northern grain region of Australia. P. thornei causes nutrient deficiency and water stress in wheat, which results in 38 million dollars’ economic loss per year in this region. Moderately resistant wheat cultivars limit reproduction of P. thornei. Investigation of bio-molecular defence in resistant wheat is challenging due to the migratory nature of P. thornei. Latest studies suggest that the resistance in wheat root acts post penetration of the nematode. However, little is known about the molecular defence mechanisms against P. thornei in resistant cultivars. Hence in the present study, modern molecular biology techniques will be used to analyze the wheat root extracts and exudates to explore various phytoanticipins and phytoalexins respectively, responsible for defence in resistant wheat. Production of phenolics and allelochemicals in susceptible and resistant wheat accessions will be investigated. The nematicidal properties of such potential bio-molecules will be tested and level of expression will be studied to learn if such compounds are constitutive or induced in response to nematode invasion. Comparative histopathology, proteomics and metabolomics will be conducted to elucidate the defence mechanism. This research will complement the quantitative trait loci (QTL) mapping of the moderately resistant trait loci discovered in several populations previously. Better understanding of natural chemical response of resistant wheats will aid deployment of resistant genes in wheat cultivars to minimize yield losses.