Designer biology to live image purine metabolism at single-cell resolution

I recently discovered the function of a previously uncharacterised gene, FAMIN, that is linked to Crohn’s disease, leprosy and arthritis.

A multifunctional purine enzyme, FAMIN is the pacesetter for purine recycling and hence determines cellular redox status, pH balance and energy production. Altogether, these control macrophage functions, such as bacterial killing and cytokine production.

Importantly, my work has established this therapeutically targetable purine pathway as a direct driver of human inflammatory disease.

However, further investigation of this pathway is currently limited by the inability to directly visualise and study purine metabolites in-situ, in real-time, and at single-cell resolution. Thus, the spatiotemporal dynamics of purine metabolism are mostly unknown.

Assessing these dynamics will be crucial in understanding how purine dysfunction emerges in individual cells and can influence disease pathogenesis, for example through affecting redox state. Samie Jaffrey has pioneered technology that could overcome this hurdle. His group has generated programmable RNA-biosensors capable of live-imaging metabolites in single cells.

I intend to learn these techniques and will engineer bespoke sensors for purine metabolites.

I shall use these biosensors to dynamically track purine metabolism, and interrogate how environmental triggers can cause the purine dysfunction seen in numerous pathological contexts including chronic inflammatory diseases.