2 Postdoctoral Positions: Nanobody-Enabled Investigation of Transient Protein-Protein Interactions
About the Steyaert lab
The Brussels based VIB-VUB Center for Structural Biology (CSB) is part of the VIB life sciences institute (VIB) and is embedded within the Vrije Universiteit Brussel (VUB). We study the structure and dynamics of macromolecular complexes in health and disease to explain their mode of action. We integrate our structural biology work with genetic and cellular studies, aiming to bridge molecular and cellular resolution. We excel in translating our discoveries into biotechnological and medical applications.
The Steyaert lab pioneered the use of Nanobodies in structural biology. By rigidifying flexible regions and obscuring aggregative surfaces, nanobody complexes warrant conformationally uniform samples that are key to protein structure determination by X-ray crystallography. The elucidation of the first GPCR structure in its active state using a conformationally selective Nanobody demonstrates the power of the Nanobody platform to generate diffracting quality crystals of the most challenging targets including membrane proteins, flexible proteins, aggregating proteins and protein-protein complexes.
Transient protein complexes play critical roles in nearly all normal cellular functions, including gene expression, cell division, protein homeostasis, and signaling. Conversely, dysfunction in the assembly, localization, or dynamics of multi-protein complexes is associated with many diseases, including cancer, autoimmune disorders, and neurodegeneration. Consequently, targeted modulation of protein–protein interaction (PPI) networks with small molecules or biologicals is one of the most promising approaches in modern drug discovery. More than 50 PPIs have successfully been targeted with small molecules but most of these are inhibitors of PPIs, disrupting binary protein complexes.
Last years, the Steyaert Lab started developing methods for the production of Nanobodies that selectively bind allosteric conformational epitopes on (transient) multi-protein complexes to modulate their composition, subcellular localization or function, rather than to disrupt the PPIs. In the coming years, we will establish Nanobody-enabled allosteric control of transient PPI networks into a robust and generic platform for the discovery of allosteric Nbs that stabilize PPIs. Such Nbs will enable solving structures of PPIs that have been resistant to investigation by X-ray crystallography, NMR or cryo-EM. We are currently recruiting 2 postdoctoral researchers to develop this technology platform.
- PhD in Biochemistry, Molecular Biology, Bio-engineering or equivalent
- Interested to work at the interface of fundamental research and technology development
- Open minded, creative and cooperative
- Proficiently in written and spoken English
Desirable but not required:
- Experience in Structural biology or antibody engineering
- Experience in omics data analysis
- A working climate where trust, (international) collaboration, and commitment are essential
- A two-year contract (extendable) with a competitive salary and benefits
- Access to state-of-the art tools and infrastructure
- A stimulating and supportive international research environment