Two Synergy ERC grants for CeNS members

Petra Schwille, CeNS member and Director at the Max Planck Institute (MPI) of Biochemistry in Martinsried, together with Bert Poolman, Professor of Biochemistry at the University Groningen, Netherlands, receives an ERC Synergy Grant for the MetaDivide project.

What is a cell? The biophysicist Petra Schwille and the biochemist Bert Poolman are dedicated to answering this question. They are world leaders in the research field of synthetic biology. Both are recreating cellular systems with just a few components in order to understand the fundamental processes of life. While Petra Schwille focuses on cell division, Bert Poolman's research focuses on metabolic processes. In the MetaDivide project, they now want to use their complementary expertise to recreate a minimal cell-like system that can divide autonomously and produce the energy to do so itself. The scientists will be funded by the European Research Council (ERC) with a total of 5 million euros over a six-year period.

How does life work in its simplest form? Delving into the biological details, this fundamental question for scientists is still unanswered in many aspects today. The cell, the smallest unit of life, is characterized by its separation from its environment, genetic reproduction, metabolism, growth, development and the ability to react to stimuli.

Petra Schwille and Bert Poolman have been studying the basic principles of life for many years – with complementary questions and research approaches. Both scientists work in the field of synthetic biology and try to construct simple biological systems “from scratch”, i.e., bottom-up, by combining and arranging individual, biochemical components in a controlled manner. Building a minimal cell from inanimate components is a dream of synthetic biology to this day.

Petra Schwille and her team have been investigating for many years which and how many components are needed for a cell to divide. To do this, they produce artificial cell envelopes. With these biological membranes, proteins produced in the laboratory interact in such a way that they enable division.

Bert Poolman, a biochemist at the University of Groningen in the Netherlands, is working on minimal metabolism. He is investigating how molecules permeate biological membranes and how the volume and the physicochemistry of the cell are controlled. He is also addressing the question of the minimum tasks that a living cell should perform and how these can be achieved with a minimal set of components.

In the MetaDivide project, Petra Schwille and Bert Poolman and their teams plan to use inanimate components, i.e., proteins and biological membranes, to create an artificial cell about the size of a bacterium that shows partial aspects of life. To do this, self-organizing membrane-active protein machines must be enclosed in the cell and driven by a self-sustaining metabolism. The artificial cell should be able to maintain a physicochemical balance and divide independently. The integration of membrane biology and minimal metabolism research in a biological system will provide scientists with a new understanding of the basic principles of life.

IDieter Braun is Professor of Systems Biophysics at LMU and a member of CeNS, the ORIGINS Excellence Cluster and spokesperson of the CRC “Molecular evolution in prebiotic environments”. His research investigates the molecular foundations of the origin of life.

It remains one of mankind's greatest mysteries, for which there are no clear scientific answers: the origin of life. What conditions had to exist on the young Earth for molecules to join together and to form the precursors of organic life and herald the beginning of biological evolution?

BubbleLife (From RNA-peptide coevolution to cellular life at heated air bubbles) aims to find answer to this fundamental question. Together with Professor Hannes Mutschler from the Technical University of Dortmund (speaker), Dieter Braun is leading the new project, which is being funded with 6 million euros over six years. “We’re an interdisciplinary team from the fields of chemistry, physics, and biochemistry, and we’ve collaborated very successfully in the past,” says the physicist.

Previous experiments have shown that one factor could have played a decisive role in the early development of life: gas bubbles that are heated up on one side. Water evaporates from their surface and sucks in molecules. These conditions are ideal for an evolutionary process in which the right molecules interact to form cell-like structures. Self-sustaining replication networks could thus have formed for the first time from individual RNA building blocks. At the same time, amino acids could have polymerized to form the first peptides, while lipids formed membrane vesicles that encapsulated these precursors of transcription and translation.

BubbleLife plans to combine these hypotheses and test them experimentally. “We are retracing the path from the Darwinian evolution of RNA and peptides to the origin of the first cells,” explains Braun. Although this presumably took millions of years to happen, the experiments to simulate the process in test tubes will take a few weeks. “Our goal is to simulate all this in a consistent environment with a small selection of initial molecules.” If all goes well, the team's interdisciplinary work will eventually lead to synthetically produced "protocell generators" that feed and encapsulate both primitive RNA replicators and modern systems of transcription and translation. “BubbleLife will hopefully fundamentally change our understanding of the origin of life on Earth – and possibly elsewhere in the universe,” says Dieter Braun.

Source: LMU Homepage and MPI of Biochemistry