Emergence and evolution of interactions between intrinsically disordered and folded proteins

Intrinsically disordered proteins (IDPs) are common in all life and involved in the intricate network of protein interactions that govern cell function.

We want to understand how such interactions emerge and evolve, including molecular mechanisms of binding-induced folding of IDPs.

While most proteins found in nature are ancient, novel proteins emerge and it is predicted that they usually are intrinsically disordered. Moreover, many of these proteins have multiple partners that compete for binding. This raises several questions, which we aim to address. What are the structures of new proteins?

What are their interaction partners?

How do protein-protein interactions evolve and is there a unifying mechanism for binding-induced folding that helps explain evolution of IDP interactions?

We use phylogenetic analyses, ancestral sequence reconstruction, protein expression and purification, protein engineering, equilibrium and kinetic methods for protein interaction, NMR, molecular dynamics simulation and phage display.

The work will be performed by a new PhD student, a research engineer and, depending on the level of funding, a researcher.

The novelty lies in the structure and functions of new proteins and in generating and testing hypothesis of unifying mechanisms in protein interactions involving IDPs.

The significance lies in the fundamental nature of the questions and their relevance for a range of biological processes such as cell signalling, virus infection and cancer.