PhD position in Bottom-up Bioenergetics and Cell Metabolism

Project Description

Bottom-up synthetic biology aims to build cell-like systems from defined molecular components. A key challenge is energy: living cells require a continuous supply of ATP and NAD(P)H to drive metabolism, biosynthesis and transport, and any synthetic cell needs the same.
The von Ballmoos group is an ambitious and interdisciplinary team that has been pioneering different ATP regeneration modules that mimic oxidative phosphorylation and photophosphorylation by co-reconstitution of relevant proteins into liposomes. Combined with enzymatic NADH regeneration, these modules can already power ATP- and NADH-dependent enzyme cascades in vitro.
Building on this, the PhD project aims to couple our energy and cofactor regeneration modules to cell-like metabolic pathways, including biosynthetic reactions such as protein production, and to understand how such coupled systems can be maintained and controlled over time. Selected reaction networks will then be encapsulated into giant unilamellar vesicles (GUVs) to create increasingly cell-like systems.
The position is embedded in a four-year SNSF project jointly awarded to the von Ballmoos group and the Stavrakis/deMello group at ETH Zürich, which develops microfluidic technologies for the generation and manipulation of synthetic vesicles. The PhD student will be part of a team working on complementary aspects of the project across both institutions.
Beyond fundamental questions, the project will design these systems with applications in mind: as self-sustaining compartments for the sustainable production of fine chemicals, or as programmable artificial cells for biomedical use.

What You Will Do

• Establish and characterise ATP- and NAD(P)H-dependent reaction networks and couple them to metabolic and biosynthetic processes, such as cell-free protein synthesis
• Purify and reconstitute membrane proteins into liposomes and GUVs
• Characterise kinetics, stability and energetic efficiency using spectroscopic techniques and fluorescence microscopy, and support this with quantitative modelling
• Collaborate closely with the Stavrakis/deMello group at ETH Zürich on microfluidic vesicle production and apply these technologies at the University of Bern

Requirements

• MSc degree in biochemistry, molecular biology, biophysics, biotechnology or a related field
• Experience in protein purification, enzymology, membrane proteins, cell-free systems, fluorescence microscopy or kinetic modelling is beneficial
• Strong interest in quantitative biochemistry, bioenergetics and synthetic biology
• Ability to work in an interdisciplinary, collaborative environment
• Good communication skills in English