Metabolism-driven division of minimal cell-like systems

Introduction

Building a synthetic cell from molecular components is one of the grand scientific and intellectual challenges of the 21st century. It requires interdisciplinary skillsets to design and integrate biochemical modules at different levels of hierarchy.

Progress in Understanding

Great progress has been made in the fundamental understanding and reconstitution of key features, such as:

1. Metabolic reaction networks
2. Replication machinery

However, their successful synergistic integration in minimal cells still lags far behind due to often largely different experimental approaches.

Project Overview

MetaDivide will bring together two groups of world-leading scientists with complementary expertise in biochemistry and biophysics to address this gap. Poolman and Schwille will combine their mastery of membrane systems and protein machineries to establish a blueprint for:

• Coupling metabolic networks to cellular modules for spatiotemporal regulation
• Force-induction for division

Research Goals

By this, we aim to reconstitute in a minimal system one of the most stunning and central features of cellular life:

• The autonomous division of proto-cellular compartments by encapsulated self-organizing macromolecular machinery, driven by a self-sustaining energy metabolism.

We will test our hypothesis that the otherwise separately researched features of life—metabolism, cell division, and genome segregation—are mechanistically linked in the emergence of cellular life.

Implications

Besides the great technical advance in synthetic biology, this will be a huge accomplishment in the understanding of biological mechanisms in today’s organisms, which in living cells are often obscured by their immense molecular complexity.

Moreover, our new fundamental insights on the main principles underlying cellular life will advance application-driven research. By elucidating the mechanisms of out-of-equilibrium reaction networks and cell division, we will obtain insights that may inform the future development of generic small molecules to curb bacterial proliferation.