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Resurrecting LUCA - Engineering of RNA-encoded Cellular Life Using Dual Evolution and Intergenomic Transplantation

Objective

Modern cellular life strictly depends on DNA as genetic material. However, a large body of evidence infers the existence of a previous, more primitive biology in which RNA also stored information in cellular entities. Recreating a living cellular fossil representing this transition from an ancient RNA world to modern DNA-based life would fundamentally advance our understanding of our biology’s history, and enable us to explore its biological properties experimentally. However, the reengineering of existing molecular systems into a viable doppelganger of the Last Universal Common Ancestor (LUCA) or one of its precursors is extremely challenging.

I propose to use a novel, combined top-down and bottom-up approach to create a modern-day doppelganger of LUCA by engineering bacterial hybrids with core cellular functions encoded on RNA. Using Darwinian Evolution as driver, my team and I will prototype and refine synthetic RNA-replicons through alternating replication in both cell-free and intracellular environments. This “dual evolution” approach will shape increasingly complex RNA networks capable of encoding complex genetic information. Following this, we will use these networks to create information-rich RNA chromosomes, enabling the transfer of essential genomic information from DNA to RNA. Finally, we will address this intergenomic transplantation by combining a novel RNA-delivery strategy with iterative rounds of genome deletion and complementation using state-of-the art CRISPR-Cas9 assisted genome editing.

The proposed research will fundamentally advance synthetic biology, and could positively answer the transformative questions: Can we create, program and evolve life-like systems that can survive in both cell-free and intracellular environments? Can we use these entities to construct an alternative biology in which central cellular activities are encoded on genomes not made of DNA?

Host institution

TECHNISCHE UNIVERSITAT DORTMUND
Net EU contribution
€ 1 234 227,61
Address
August Schmidt Strasse 4
44227 Dortmund
Germany
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
Region
Nordrhein-Westfalen Arnsberg Dortmund, Kreisfreie Stadt

Beneficiaries (2)

TECHNISCHE UNIVERSITAT DORTMUND
Germany
Net EU contribution
€ 1 234 227,61
Address
August Schmidt Strasse 4
44227 Dortmund
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
Region
Nordrhein-Westfalen Arnsberg Dortmund, Kreisfreie Stadt
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Participation ended

Germany
Net EU contribution
€ 265 772,39
Address
Hofgartenstrasse 8
80539 Munchen
Activity type
Research Organisations
Non-EU contribution
€ 0,00