How organelles develop in cells? The DFG funded 'Interfacial Cell biology' Emmy Noether Group investigates this question in the framework of the Professorship for Biochemistry and Molecular Biology at the Faculty of Medicine and University Hospital Cologne of the University of Cologne.

Particularly, we focus on morphogenic processes that are mediated by contacts between emerging liquid compartments (also known as biomolecular condensates, membrane-less organelles or droplets) and conventional cellular structures such as membrane-bound organelles. Our aim is to achieve a comprehensive physico-molecular knowledge of the underlying condensate-substrate interaction, which will inform the precise manipulation of cellular processes in basic research and medical applications. The Interfacial Cell Biology Group will focus on these key areas:

Autophagy: The autophagosome is the key organellar component of autophagy, the highly-conserved intracellular bulk degradation pathway. During autophagy, autophagosomes isolate cellular material within curving membrane sheets, which are then delivered to the lysosome/vacuole for degradation and metabolite recycling. Recently, we discovered that phase separated condensates mediate autophagosome formation via wetting interactions. This complex mechanism is controlled by condensate and membrane physical properties, their molecular identities and results in several distinct pathways of recycling material selection and autophagosomal morphologies (Nature 2020, Nature 2021, Autophagy 2021). This discovery showed for the first time that capillary force is important in cell-physiological processes.

Embryogenesis: Most protein eaten by humans and animals originates from plants, in particular seeds including soy bean and wheat. During their development, seeds accumulate protein in dedicated organelles that are known as protein storage vacuoles. Recently, we discovered that micrometer-sized liquid condensates containing storage proteins form within the lumen of vacuoles through phase separation at specific stages of plant embryo development. These condensates wet the tonoplast (vacuolar membrane), mediate tonoplast remodeling and formation of multiple protein storage vacuoles (PNAS 2021, JCB 2021).

Our group follows a highly collaborative, iterative approach and employs a broad spectrum of methods, ranging from cell biology and biochemistry via mathematical modelling to biophysics, interfacial sciences and synthetic biology. Drawing on the physiological relevance of in vivo data, our multi-faceted approach will reveal fundamental insights into the physico-molecular mechanisms that link phase behaviour to morphogenic processes in cells.

(Keywords: membrane bending, membrane remodelling, membrane shaping, phase separation, LLPS, biomolecular condenstates, wetting, capillarity, capillary force)