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Autonomous Cellular Computers for Diagnosis

Project description

Cell-based biosensors for advanced diagnosis

Current diagnostic technologies for multiple biomarkers are complex and costly, but living cells offer a scalable and affordable solution. Funded by the European Research Council, the COMPUCELL project proposes to engineer chimeric receptors in the bacterium Bacillus subtilis to detect biomarkers, utilising sensing domains from antibodies. The key objective is to advance synthetic biology and explore biological computers capable of undertaking multiplexed biomarker analysis. COMPUCELL will deliver a prototype for the diagnosis of diabetic nephropathy in urine, but the reusable sensing platform has the potential for use in other applications including environmental monitoring.

Objective

Early diagnostics based on multiple biomarkers is key in numerous diseases, yet current technologies for multiplexed detection are complicated and expensive. Living cells detect and process various environmental signals in parallel and can self-replicate, presenting an attractive platform for scalable and affordable autonomous diagnostic devices. In this project, I will apply my expertise in synthetic biology, the rational engineering of biological systems, to build cell-based biosensors for multiplexed diagnosis using the non-pathogenic bacterium Bacillus subtilis.

In a first research line, I will conceive a scalable detection machinery by engineering chimeric receptors detecting extracellular biomarkers via sensing domains derived from antibodies. In a second research line, I will implement bio-molecular computing systems operating within and across bacterial cells to perform multiplexed biomarkers analysis. I will deploy in B. subtilis biomolecular logic gates and will engineer specific cell-cell communication systems to perform distributed multicellular computation in a bacterial consortia.

My project is highly interdisciplinary and is at the cross-roads of genetic engineering, structural biology, biophysics, modeling, and clinics. On foundational point of view, I will make several breakthrough contributions to synthetic biology: (i) Advancing engineering frameworks for the Gram-positive model, B. subtilis. (ii) Pushing the limits of custom-ligand detection by engineered cells (iii) Exploring the frontiers of man-made biological computers. On an applied point of view, I plan to deliver a first prototype for the urinary diagnostic of diabetic nephropathy, a major complication of diabetes. Because of the modular design principles applied, my sensing platform will be reusable to diagnose other pathologies as well as for applications requiring custom-detection and bio-molecular computation like targeted therapy, drug delivery, or environmental monitoring.

Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution
€ 1 500 000,00
Address
RUE DE TOLBIAC 101
75654 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost
€ 1 500 000,00

Beneficiaries (1)