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H2020Doctoral network2018–2023

ProtoMet · Protometabolic pathways: exploring the chemical roots of systems biology

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2018-11-01 → 2023-10-31
EU contribution
€2,174,048
Participants
11
Scheme
MSCA-ITN

Lines connect the coordinator with its partners.

Results in brief

Protometabolic pathways: exploring the chemical roots of systems biology

We assembled a team of early-stage researchers and principal investigators to gain insight into the origins of life through the lens of metabolism. Very little is known about how life began because we lack artifacts from that era that can be directly interrogated. Similarly, skillful bioinformaticians can take us back in time to understand likely scenarios of evolution from ancient cells that were nevertheless quite complex. However, such analyses cannot directly reveal the chemistry that led to the emergence of the first, primitive cells. Our ESRs approached this problem by exploiting the tools of chemistry and microfluidics with input from philosophy. In this way, the team sought to recreate plausible scenarios that could have contributed to the emergence of life. To do so, ESRs focused on uncovering prebiotic analogues of central metabolic pathways necessary for the exploitation of fuel and the synthesis of the building blocks of life. Emphasis was also placed on the compartments that house living cells, since compartments are key cellular constituents for metabolism and Darwinian evolution. In addition to informing our understanding of ourselves and our planet, this work also gave ESRs a solid grounding in the chemistry that underpins biology with clear applications to synthetic biology and medicinal chemistry in either industry or academia.

Data: CORDIS, © European Union

Project objective

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.

Original text from CORDIS.

Participants

  • UNIVERSITA DEGLI STUDI DI TRENTO · TrentoCoordinatorItaly
  • CHERRY BIOTECH · MONTREUILFrance
  • EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH · ZuerichSwitzerland
  • ELVESYS · PARISFrance
  • KUTXAGESTION ZERBITZUAK S.L. · SAN SEBASTIANSpain
  • MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV · MUNCHENGermany
  • METALLOPHARM LLC · DelawareUnited States
  • NANOVEX BIOTECHNOLOGIES SL · LlaneraSpain
  • UNIVERSIDAD DEL PAIS VASCO/ EUSKAL HERRIKO UNIBERTSITATEA · LeioaSpain
  • UNIVERSITE DE STRASBOURG · StrasbourgFrance
  • UNIVERSITY COLLEGE LONDON · LondonUnited Kingdom

Links

Data: CORDIS, © European Union