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The origin and evolution of Life in the universe

Periodic Reporting for period 1 - oLife (The origin and evolution of Life in the universe)

Berichtszeitraum: 2019-04-01 bis 2021-03-31

One of the largest questions of humankind is where we originate from and how we evolved. While at the disciplinary level some aspects of the origin of life question have been unravelled, the answers obtained thus far are fragmentary and far from complete. With our unconventional trans-disciplinary approach we now address this question. The oLife Fellowship Programme brings together a wide range of disciplines ranging from molecular biology to astrophysics, and from evolutionary ecology to biochemistry. Eighteen talented postdocs collectively conduct interdisciplinary research to By joining forces we enhance our understanding of the origin, evolution, distribution and development of life in the universe, with the ultimate goal of developing methods for steering life on a human-dominated planet.

Next to their interdisciplinary research projects, the oLife fellows follow a joint research and training programme, consisting of scientific lectures, academic and professional skills training, career guidance, and teaching and supervision of students. In addition, they have the opportunity to go on secondments with leading industrial, academic and non-profit partner organisations of the oLife Fellowship Programme. The aim is to equip and prepare the fellows for their further career, both within and outside academia.
The first period 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. The Covid-19 pandemic required flexibility and adaptation, both from the fellows and the Fellowship Programme. Nonetheless, all fellows have successfully commenced their research activities. Progress can be seen on three fronts, corresponding to the molecular, the cellular, and the planetary scale.

At the molecular level, we are 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. We find 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 micrometers. 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 study 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 are setting up a library of chemical compounds that display the desired kind of activity.

We are also creating 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, we carry out experiments on the effect of molecular structure on biological functionality. We perform Traveling Wave Ion Mobility Spectroscopy to see how the structure of biomolecules differs from that their abiotic cousins.

On cellular scales, we are studying:
- The fusion of bacteria without cell walls, which are thought to resemble the earliest forms of life on Earth. We find that such fusion is inefficient, and plan 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 are the first to do so for living systems such as fungi and yeast cells.
- How communication between cells influences natural selection of organisms. We use atomic force microscopy to measure mechanical stress on vesicles originating from cells.
- The transport of molecules across cell membranes. We extract transporter molecules from bacteria and uses cryogenic electron microscopy to image how they modify membrane structures to allow transport of food and waste. A first paper just appeared in PNAS; we also contributed to another paper.
- The variability of the protein translation rate during the division cycle of yeast cells. Using fluoresence microscopy of live yeast cells in microfluidic chips and computational analysis of proteomics data, we aim to understand the relation between metabolic and cell cycle oscillations.

We also aim to mimic 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, we are studying:
- Which observations of exoplanets can be used as signs of extraterrestrial life. Using decades worth of satellite imaging of the Earth, we search for 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 are preparing a follow-up article presenting a list of best planets to search for moons around.

Regarding early Earth biochemistry, we are studying:
- 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 measure 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 focus on the enzymes to create both kinds of lipids, both in synthetic and in living systems.
By recruiting and seconding 18 highly qualified fellows, research into the origins and evolution of life will be boosted on both a regional and national level. The oLife Fellowship Programme provides a solid and structured framework to further explore and deepen interdisciplinary collaboration in this area. The combined approach and efforts are expected to lead to a much higher efficiency and advancement of results.
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