Jonathan Jones investigates mechanisms of disease resistance in plants, and how plant pathogens overcome host resistance using defence-suppressing ‘effectors’. He has isolated and characterized many resistance (R) genes that encode plant immune receptors, and revealed how certain intracellular receptors recognise pathogen molecules and activate defence. He is keenly interested in parallels between mechanisms of animal and plant NLR intracellular immune receptors, and has pioneered genomics methods to accelerate R gene cloning and the analysis of plant immune receptor diversity and evolution.

Jonathan investigates how the Arabidopsis (thale cress) RPS4/RRS1 NLR receptor pair recognises bacterial effectors, and mechanisms of Arabidopsis resistance to the oomycete pathogens that cause downy mildew and white rust (Albugo). Arabidopsis resists Brassica-infecting races of Albugo (so-called "non-host resistance"). The potato relative Solanum americanum resists all races of the late blight pathogen Phytophthora infestans. The Jones group is isolating multiple genes which encode immune receptors that underpin these non-host resistances, with the aim of using genes from wild crop relatives to convert crops into non-hosts for their pathogens.

Jonathan engages with the public as a strong advocate for controlling crop disease using R genes from wild relatives introduced via genetic modification and/or gene editing. He conducts field trials to evaluate the use of such R genes to confer late blight resistance in GM potato. He coauthored "Reaping the Benefits" and was elected Foreign Associate of US NAS in 2015.