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Understanding how prebiotic chemistry gave rise to life as we know it represents one of the greatest enduring mysteries. The complete absence of a historical record requires the collaboration of scientists from different disciplines with access to advanced tools in order to make any meaningful progress. Here, we plan to exploit this tremendous challenge to train a new generation of scientists to think big, but also to work methodically and logically alongside colleagues from academia and industry. Eight Early-Stage Researchers (ESRs) will be recruited to work in laboratories with expertise in systems chemistry, synthetic biology, microfluidics, and science philosophy to develop together a reconstituted protometabolism within compartments consisting of coacervates, vesicles, coacervate containing vesicles, and compartments etched into microfluidic chips. The underlying protometabolism will be composed of triose glycolysis and a reverse citric acid cycle and will be regulated by (metallo)peptide catalysts.

Importantly, the protometabolism will support the maintenance of the compartment that houses the protocell. The ESRs that primarily focus on the construction of compartments that mimic protocellular structures will gain firsthand experience in how their formulations could be exploited as drug delivery vehicles through secondments at partner organizations. Similarly, the ESRs that develop (metallo)peptide catalysts will apply their newfound skills to the development of drug molecules through a secondment at a company that specializes in metallodrug formulations.
Ultimately, by becoming experts in elucidating the chemical underpinnings of all known living cells, the ESRs will be extremely well positioned to enter a wide variety of research fields from synthetic biology to medicinal chemistry in either industry or academia.

In order to achive our goal, the ProtoMet Project is structured into six Work Pakages, as followed described:

WP1Prebiotic pathways
WP2Compartmentalised protometabolism
WP3Understanding and exploiting the origin of life
WP4ProtoMet Training
WP5 WP5 Dissemination, Communication and Outreach
WP6Coordination, Management and IPR
WP7Ethics requirements

The focus of the research will be carried out on the followings workpachages

  • WP1 will unravel how chemical reactions lead to networks of protometabolic reactions.
  • WP2 will look at the emergence of compartments from catalysts and products derived from metabolism and, consequently, the influence of compartmentalisation on metabolic rates.
  • WP3 will experimentally and theoretically put the pieces together.

The WPs are strictly intertwined and interact one with the other, the following figure describes the interactions among the WPs.