The start of the project was mainly focused on setting up the programme management structures, recruiting 18 talented and motivated fellows, and facilitating a good start to their research and training activities. After that the Covid-19 pandemic required flexibility and adaptation, both from the fellows and the Fellowship Programme. Nonetheless, all fellows successfully commenced and completed their planned research activities during the total project period . Progress was seen on three fronts, corresponding to the molecular, the cellular, and the planetary scale.
At the molecular level, the Fellows have been studying:
- Systems-level phenomena which may explain why aggregates have more or other functionality than their constituent parts, with a focus on specific chemical systems to explain their biological function by principles such as autocatalysis. The evolution of self-replicating chemical systems and its dependence on prior conditions was studied. We found that chirality of the building blocks greatly enhances the efficiency of such systems.
- The development of compartments from organic building blocks on scales from nano- to micrometres. Our first results about microdroplets and chemical signalling were presented at the 2021 ICMS symposium in Eindhoven.
- The evolution of organisms that lived billions of years ago, using the extreme stability of lipids. We studied the synthesis of various lipid types and the way how they can be used to create cell membranes.
- How autocatalytic reactions can lead to homochirality, which is considered essential for molecular recognition and biosynthesis. We have set up a library of chemical compounds that display the desired kind of activity.
The Fellows have also created computer models of the interaction between RNA molecules and proteins. This work focuses on the formation of biomolecular condensates by the separation of liquid phases, mediated by RNA-protein interactions; a first paper has appeared.
In addition, the Fellows have carried out experiments on the effect of molecular structure on biological functionality. In particular, they performed Traveling Wave Ion Mobility Spectroscopy to see how the structure of biomolecules differs from that of their abiotic cousins.
On cellular scales, the Fellows have been studying:
- The fusion of bacteria without cell walls, which are thought to resemble the earliest forms of life on Earth. We found that such fusion is inefficient, and set up further experiments to understand how early organisms could exchange genetic material, which is crucial for complex life forms to develop.
- The evolution of amino acid transporters and their dependence on the type of host organism. We were the first to do so for living systems such as fungi and yeast cells.
- How communication between cells influences natural selection of organisms. We used atomic force microscopy to measure mechanical stress on vesicles originating from cells.
- The transport of molecules across cell membranes. We extracted transporter molecules from bacteria and used cryogenic electron microscopy to image how they modify membrane structures to allow transport of food and waste. Several papers appeared in PNAS and other journals.
- The variability of the protein translation rate during the division cycle of yeast cells. Using fluorescence microscopy of live yeast cells in microfluidic chips and computational analysis of proteomics data, we have clarified the relation between metabolic and cell cycle oscillations.
We have also mimicked the energy household of living cells in artificial structures based on membrane proteins and lipid vesicles. We have managed to create synthetic organelles which both provide and consume fuel, and even remove waste products.
Finally, at the planetary level, our Fellows have been studying:
- Which observations of exoplanets can be used as signs of extra-terrestrial life. Using decades worth of satellite imaging of the Earth, we have identified patterns which are indicative of biological activity and not just temperature or water/land differences.
- The habitability of moons around extrasolar planets. We have published a first paper on the orbital stability of exomoons, and a follow-up article presenting a list of best planets to search for habitable moons around.
Regarding early Earth biochemistry, our Fellows have studied:
- The evolution of enzyme functions in cells, in particular for removal of toxic molecules. We have managed to trace this functionality back for ~3 billion years, when the Earth atmosphere did not yet contain significant amounts of oxygen. This research line has led to one paper as lead author and two papers as co-author.
- Mechanisms how RNA molecules may have originated on the early Earth as the starting point of genetics. We have measured the ability of sugars and other building blocks to form larger supramolecular structures.
- The origin of eukaryotic cells from bacterial and archaeal ancestors, which use different lipids for their membranes. We have focused on the enzymes to create both kinds of lipids, both in synthetic and in living systems.
