Project 21736 Building and directing life
Hosting Research group: Prof. Dr. A. Kros1, Dr. D. Rozen2, Dr. H. Youk3, Dr. Dr. D. Claessen2
1 Leiden University, Leiden Institute of Chemistry
2 Leiden University, Institute of Biology
3 TU Delft, Department of Bionanoscience

Evolution on steroids

Life on Earth has evolved increasing levels of complexity. Part of this complexity is due to the slow accumulation of mutations that gradually cause organisms to become increasingly suited to the environments in which they live. However, in addition to these slow changes, a series of so-called “major transitions” in evolution have led to more fundamental alterations in organismal complexity. During major transitions, free-living organisms/entities abandon their autonomy and join together into a new higher-level whole. During each of these transitions, formerly discrete units gave up their independence to enter mutually interdependent relationships. Two organisms with aligned evolutionary fates transitioned to one. While recent theoretical studies have started to examine various aspects of these transitions, we still have very limited experimental understanding of the processes driving major transitions.

Here, we will use a powerful combination of synthetic biology, mathematical modelling, supramolecular chemistry and experimental evolution to examine the earliest steps of the major transition from simple (single genome) to complex cells (numerous chromosomes). To this end, we will exploit the unique benefits of so-called L-forms, which are bacterial variants lacking a cell wall. Interestingly, L-form cells generated from a wide range of bacteria have a strikingly similar mode of proliferation, which is based on biophysical principles and no longer depends on the conserved cell division machinery. As such, the mode of L-form proliferation of L-form cells has been suggested to resemble that of early life forms or primordial cells, and which operated before cells had evolved a cell wall.

Excitingly, the host lab in Leiden has shown that L-form cells can be easily fused to form polyploid cells containing multiple chromosomes. For this, we make use of a synthetic membrane fusion system inspired by the natural occurring SNARE-proteins, which are the molecular machinery driving vesicle fusion in eukaryotic cells. This technology enables us to engineer synthetic hybrid cells containing multiple chromosomes from different species, whereby the resulting cells will have a mixed chemistry. Using this adaptable system, we will first develop an experimentally parameterized mathematical framework to examine the short and long-term evolutionary interactions between coexisting chromosomes. Next, we will test these predictions by elucidating the dynamics, stability and genetic underpinnings of transitions in complexity using experimental evolution.

The results from this study will advance our understanding of the evolution of complex life. Additionally, they will help to identify underlying principles required to sustain designer cells that are robust in the face of environmental change. The impact of this work thus spans several fields including evolutionary biology, microbiology, synthetic biology and molecular biology. In the long term, we envision to use such synthetic cells as cell factory for the production of new medicines.

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