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Engineering an artificial immune system with functional components assembled from prokaryotic parts and modules

Engineering an artificial immune system with functional components assembled from prokaryotic parts and modules

Objetivo

The objective of this project is to overcome current limitations for antibody production that are inherent to the extant immune system of vertebrates. This will be done by creating an all-in-one artificial/synthetic counterpart based exclusively on prokaryotic parts, devices and modules. To this end, ARISYS will exploit design concepts, construction hierarchies and standardization notions that stem from contemporary Synthetic Biology for the assembly and validation of (what we believe is) the most complex artificial biological system ventured thus far. This all-bacterial immune-like system will not only simplify and make affordable the manipulations necessary for antibody generation, but will also permit the application of such binders by themselves or displayed on bacterial cells to biotechnological challenges well beyond therapeutic and health-related uses. The work plan involves the assembly and validation of autonomous functional modules for [i] displaying antibody/affibody (AB) scaffolds attached to the surface of bacterial cells, [ii] conditional diversification of target-binding sequences of the ABs, [iii] contact-dependent activation of gene expression, [iv] reversible bi-stable switches, and [v] clonal selection and amplification of improved binders. These modules composed of stand-alone parts and bearing well defined input/output functions, will be assembled in the genomic chassis of streamlined Escherichia coli and Pseudomonas putida strains. The resulting molecular network will make the ABs expressed and displayed on the cell surface to proceed spontaneously (or at the user's decision) through subsequent cycles of affinity and specificity maturation towards antigens or other targets presented to the bacterial population. In this way, a single, easy-to-handle (albeit heavily engineered) strain will govern all operations that are typically scattered in a multitude of separate methods and apparatuses for AB production.

Investigador principal

Víctor De Lorenzo Prieto (Prof.)

Institución de acogida

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

Dirección

Calle Serrano 117
28006 Madrid

España

Tipo de actividad

Research Organisations

Aportación de la UE

€ 2 422 271

Investigador principal

Víctor De Lorenzo Prieto (Prof.)

Contacto administrativo

Guillermo Sanjuanbenito (Mr.)

Beneficiarios (1)

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AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

España

Aportación de la UE

€ 2 422 271

Información del proyecto

Identificador del acuerdo de subvención: 322797

Estado

Proyecto cerrado

  • Fecha de inicio

    1 Mayo 2013

  • Fecha de finalización

    30 Abril 2019

Financiado con arreglo a:

FP7-IDEAS-ERC

  • Presupuesto general:

    € 2 422 271

  • Aportación de la UE

    € 2 422 271

Organizado por:

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

España