– Proposal full title: Programmable nucleic acid toolkits for cell-free diagnostics and genetically encoded biosensing
The biological complexity of tumours and the large diversity of diagnostic biomarkers call for the development of innovative analytical tools that can detect multiple targets in a sensitive, specific and low-cost way and allow real-time monitoring of disease pathways and therapeutic effects. This project will address these needs by developing rationally designed programmable nucleic acid modules that respond to a wide range of molecular markers and environmental stimuli through innovative nature-inspired mechanisms and that can be orthogonally wired to provide cell-free point of care diagnostic kits and genetically encodable biosensors.
The project is split into three major Objectives. These objectives present different degrees of complexity following a trajectory that goes from pure curiosity-driven (Objective 1) to more applied research (Objectives 2-3):
Objective 1 (O1): TRICKS: Recreate nature-inspired tricks using synthetic RNA.
Objective 2 (O2): MODULES: Create a library of programmable responsive nucleic acid modules.
Objective 3 (O3): TOOLS: Develop cell-free diagnostic kits and genetically encoded biosensors.
O1 will define the mechanisms and strategies that will be used to program and control the responsive RNA modules. This objective will require a strong know-how in supramolecular chemistry, synthetic biology, biochemistry and organic chemistry. O2 will use the characterized tricks to create a library of programmable nucleic acid-based responsive modules. Finally, in O3 the RNA-responsive modules will be assembled to develop novel biosensing platforms.