Welcome to REPIN - Rethinking Protein-Protein Interactions (cover)

REPIN is a cross-disciplinary endeavour with the ambition to widen the definitions and rules for protein interactions. This project aims to foster a lasting renaissance in basic and applied protein chemistry encompassing intrinsically disordered proteins.

Research and discoveries are mostly driven from established concepts and searches around normality. Together with mental borders from paradigms, this causes rare advances and breakthroughs. The lock-and-key model for protein interactions postulated in 18941 followed by the induced-fit model in 19582 have been instrumental for our understanding of molecular communication and effective for drug developments. However, with the discovery of intrinsically disordered proteins (IDPs), these models have met limitations and research into how molecular interactions can be achieved in the absence of form is critically required.




In REPIN, we take on the challenge to uncover hitherto unknown principles of intrinsic disorder (ID)-based protein interactions. We do this by developing novel concepts and by fostering a renaissance of classic protein chemistry terms including specificity, allostery, polyelectrolyte behaviour, and allovalency by disorder. The understanding of molecular communication can be revolutionized but it requires a rethinking of protein interactions in the frame of molecular disorder

New concepts and vocabulary in protein chemistry await discovery from studies of carefully selected ID-based interaction model systems.

REPIN Hypothesis

THE IDEA is to establish a multi-scale experimental protein chemistry strategy ranging from studies at the single molecule level over ensembles to whole organisms, to capture features of ID-based interactions, which manifest themselves at different levels of resolution. The know-how and experimental and theoretical aptitudes in REPIN enable us to approach disorder in multiple selected systems covering all time- and length scales at depth.

The vision is to change our conception of molecular communication through overcoming contemporary challenges in protein interactions.

The aims are to develop concepts and models for ID-based interactions that incorporate new as well as classic protein chemistry terms.

Our ambitions are to widen the definitions and rules for protein interactions and to foster a lasting renaissance in basic and applied protein chemistry encompassing ID.

REPIN is funded by a Novo Nordisk Foundation Challenge grant.


The REPIN consortium includes Prof. Birthe B. Kragelund (BBK), Prof. Benjamin Schuler (BS), Prof. Karen Skriver (KS), and Prof. Rasmus Hartmann-Petersen (RHP)  and includes a core collaborative base of Prof. Lise Arleth (LA) and Robert Best (RB). Expert competences cover structural biology, protein chemistry, protein folding, biophysics, biochemistry, genetics, and applied bioinformatics.

Birthe B. Kragelund, ORCID: 0000-0002-7454-1761, is professor of biostructural NMR spectroscopy at the University of Copenhagen and head of REPIN. From a background in protein NMR spectroscopy, protein folding and protein chemistry, and educated at the Carlsberg Laboratory, BBK has worked to further the understanding of protein disorder and functional dynamics and their impact on biology. Through cross-disciplinary collaborations, she has propagated knowledge to fields outside structural biology, and pioneered the characterization of intrinsically disordered proteins (IDPs) in particular in membrane proteins. Her research addresses protein intrinsic disorder at several levels, and includes the associated fields of protein folding and interactions, where she focuses on disorder in cellular signaling through integrative methods. Included in her 100+ peer-reviewed papers, she has also published protein chemistry methods, reviews that bridge across fields, book chapters, as well as educational outreach papers.

BENJAMIN SCHULER, ORCID: 0000-0002-5970-4251, is professor of Molecular Biophysics at the University of Zurich, CH, and has a background in biochemistry and biophysics. BS is an expert in protein structure and dynamics, especially using single-molecule spectroscopy. By developing new single-molecule methods and integrating them with a broad range of complementary biochemical and biophysical techniques, he has been able to establish a quantitative understanding of IDPs and protein conformational dynamics on
previously inaccessible length- and timescales. Recently, BS has started to focus on the functional properties of IDPs, especially their interactions with other biomolecules. Key competences include protein biophysics, single molecule spectroscopy, IDPs, protein folding and protein dynamics.

RASMUS HARTMANN-PETERSENORCID: 0000-0002-4155-7791, is professor at BIO, UCPH. With a background in protein chemistry and yeast genetics he has established himself as an internationally recognized expert in regulated protein degradation. Through biochemical, structural and genetic studies RHP has identified and characterized several proteins involved in the ubiquitin-proteasome system, including new proteasome subunits and co-factors, a novel intrinsically disordered ubiquitin-binding protein, which is highly multifunctional and broadly involved in degradation and signaling. Key competences include IDPs, genetic screens and proteomics, and detailed cell biological, structural and biophysical studies.

KAREN SKRIVER, ORCID: 0000-0003-2225-4012, is professor at BIO, UCPH, and with a background in protein chemistry, biochemistry, and plant biology KS has established herself as an internationally recognized expert in macromolecular interactions within transcriptional networks. Through biochemical, structural and transgenic studies KS has characterized functional elements of gene-specific transcription factors (TFs) regulating stress responses and development. This includes identification of a DNA-binding-site landscape and regulatory network for NAC transcription, structures and linear motifs of intrinsically disordered NAC regions providing clues to the interactome of a cellular and evolutionary patterns of disorder profiles, and whole organism effects of changed TF-levels in vivo. Her studies contribute to a platform for revival of classical biochemical concepts, developed for folded proteins, in the light of ID. Key competencies include biochemical and protein chemistry approaches followed by detailed structural, biophysical, and whole organisms in vivo studies.


REPIN offers an ambitious and inspiring crossdisciplinary workplace with engaged and enthusiastic colleagues and challenging projects. If you wish to join our venture, feel free to contact one of the core members and present them with your project, or hear about openings in existing or starting projects - we always have bachelor or master's projects at hand.

Occasionaly, we also have funded PhD or postdoc positions available. In that case, you can find more information and apply on the UCPH job portal: https://employment.ku.dk/





Funded by:

Novo Norsisk Foundation

REPIN has received six year funding from the Novo Nordisk Foundation Challenge programme 

Project: REPIN - Rethinking Protein-Protein Interactions
Period:  2019-2025


Prof. Birthe B. Kragelund
Copenhagen Biocenter
Ole Maaløes Vej 5
DK 2200 Copenhagen N
Phone:  +4535322081
E-mail: bbk@bio.ku.dk 
KU research profile: Link