CoIN members
The members of CoIN represent laboratories located throughout Copenhagen. You can read more about their research and find links to their homepages below.
Bente Vestergaard, BioSAXS group, University of Copenhagen
Homepage: https://ilf.ku.dk/ansatte/?pure=da/persons/307419IDP relevant research: Structural characterisation of alpha-synuclein (aSN).
aSN is an IDP, abundant in the cytosol of several celltypes and particularly dopaminergic neurons, well-known for it’s implication in the development of Parkinson’s disease, where amyloid fibrils (large highly ordered protein aggregates) accumulate in the brain, and where pre-fibrillar species may play a prominent role in the associated neurodegenerative actions. aSN is known to adapt to a partially helical conformation during lipid membrane interactions, and to a partially beta-strand conformation in the fibril states. We have particular focus on the structural aspects of the aSN fibrillation reaction, and a more recent strong focus on the structural aspects of aSN:membrane interactions.
Birthe B. Kragelund, Linderstrøm-Lang Centre, University of Copenhagen
Homepage: www.bio.ku.dk/bms/bbk
IDP relevant research: The Kragelund group combines biophysical studies with cell-biology to study how intrinsic disorder underlie cellular decision making. In particular they address the role of intrinsic disorder in membrane proteins and study the interplay with membrane constituents and signaling molecules. Mainly based on NMR methodology in combination with a suite of other biophysical techniques they aim to decipher how fuzziness is deterministic for protein recognition and protein function.
Elena Papaleo, Danish Cancer Society
Homepages: https://www.cancer.dk/research/dcrc-research-units-and-groups/computational-biology-laboratory/, https://sites.google.com/site/cblcancerdk/IDP relevant research: Elena Papaleo is the group leader of the Computational Biology Laboratory (CBL) at the Danish Cancer Society (DCRC). CBL research focuses on the study of conformational ensembles of intrinsically disordered proteins or disordered tails, loop and linker of folded proteins that play crucial roles in cancer pathways. We are especially interested in the effects induced upon post-translational modifications and cancer-related mutations on the conformational ensemble of IDPs in their free and bound states. We are also studying key scaffolding proteins working at the cross-road between autophagy and cell proliferation in collaboration with the Unit of Cell Stress and Survival and the Unit of Cell Death and Metabolism at DCRC. We use enhanced sampling molecular dynamics simulations (including metadynamics, NMR-driven sampling and replica exchange) and bioinformatics tools to unravel PTM-modulated structural motifs in IDPs. We work in tight collaborations with experimental groups from different fields, including cellular biology, biochemistry, and biophysics in Denmark and abroad.
Karen Skriver, Linderstrøm-Lang Centre, University of Copenhagen
Homepage: https://www.bio.ku.dk/bms/ks/IDP relevant research: Intrinsically disordered transcription factors and folded hub proteins
Our studies focus on the mechanism of interactions between intrinsically disordered plant transcription factors and structured cellular hubs. The results from biophysical characterization are translated to the organismal level to improve understanding of essential cellular interactomes.
Homepage: https://www.bio.ku.dk/bms/kllIDP relevant research: The Lindorff-Larsen group combines molecular dynamics and Monte Carlo simulations with experiments to study the relationship between protein structure, dynamics and function. A key goal is to be able to provide a realistic and useful description of the complicated ensembles of conformations a protein may take, and to use this to understand its biological behaviour. In the context of intrinsically disordered proteins and intrinsically disordered regions we are developing novel methods to sample these efficiently by computation, and to use information from e.g. NMR and SAXS to understand how structural preferences are determined and how they affect functions such as binding and regulation.
Homepage: https://www.bio.ku.dk/staff/ellgaardIDP relevant research: We are interested in the role of IDP’s in recognizing substrates for proteasomal degradation, for instance IDP’s present in proteins of the ER-associated degradation (ERAD) pathway and in E3 ubiquitin ligases.
Martin Willemoës, Linderstrøm-Lang Centre, University of Copenhagen
Homepage: https://www.bio.ku.dk/bms/mwIDP relevant research: We use isothermal titration calorimetry to determine the thermodynamic paramters of intrinsically disordered proteins. The advantage of ITC in studying peptide and protein interactions within IDP domains is that no labeling is required and that the true thermodynamics of the interactions are obtained. This allows us to analyse the entropi and enthalpy effects of side chain substitutions and suggest mechanisms for the interaction between ID regions and their binding sites.
Meike Burow, Center of Excellence for Dynamic Molecular Interactions (DynaMo), University of Copenhagen
Homepage: https://dynamo.ku.dk/people/burowIDP relevant research: “Plant metabolism is continuously evolving new biosynthetic pathways that provide novel biotic and abiotic resistance mechanisms, but relatively little is known about the corresponding evolution of the necessary regulatory factors. We study how new and specific regulatory patterns arise from changes in the composition of transcription factor complexes and whether this occurs through rapid evolution of transiently structured protein regions.”
Homepage: https://www.cancer.dk/research/statistics-bioinformatics-registry/sbrresearch/IDP relevant research: IDP oncogenic CIP2A and PP2A involved in metabolism and autophagy regulation in cancer.
Inhibition of protein phosphatase 2A is an hallmark of cellular transformation. Cancer cells express highly IDP proteins such as CIP2A and SET to directly suppress PP2A activity engaged to control major growth, survival and cell death signaling pathways. Little is known about these endogenous highly expressed PP2A inhibitor CIP2A and SET functions. Recently, we investigated the role of CIP2A in cancer cell transformation and survival. We characterized mechanism behind CIP2A in regulating of mTORC1, c-Myc and AMPK pathways, three major cancer cell metabolism regulating pathways, trough PP2A inhibition. Currently, we characterize structural diversity and numerous post-translational modifications, such as phosphorylation, ubiquitination and acetylation of CIP2A in order to understand how it associates with such a major signaling nexuses. Also, what is the molecular regulatory and inhibitory mechanism behind association between CIP2A and PP2A. Characterization of functional motifs that serve as a platform between CIP2A, PP2A, AMPK, mTORC1 and c-Myc association is our goal.
Rasmus Hartmann-Petersen, Linderstrøm-Lang Centre, University of Copenhagen
Homepage: https://www.bio.ku.dk/bms/rhpIDP relevant research: We focus on the role of IDPs in intracellular protein degradation via the ubiquitin-proteasome system, using yeast genetics, proteomics and structural techniques to probe their function.
Stine Falsig Pedersen, Cell and Developmental Biology, University of Copenhagen
Homepage: https://www1.bio.ku.dk/staff/FalsigPedersen/IDP relevant research: The core interest of the Pedersen group is acid-base transport proteins of the solute carrier (SLC) superfamily. Our strategy is to study a few selected SLCs using a “vertical” approach in which we address questions from the regulation of their transcription and translation, their posttranslational regulation, structure, cell biology, and finally to their function and pathology-related dysfunction in animal models. This allows us to use, for instance, understanding of how posttranslational regulation affects SLC protein structure, dynamics, and interactions, to gain mechanistic insight in the dysregulation of these proteins in disease. The SLC family most extensively studied in our group is the SLC9A family of Na+/H+ exchangers, which exhibit a partially evolutionally conserved intrinsically disordered (ID) region in their C-terminal tail, which we have shown is very important for the regulation and function of central members of this family. Our current focus is to elucidate how evolution of ID in the SLC9A family may underlie the differences in localization, regulation and function of the various family members, with particular focus on how ID orchestrates molecular “hub” functions of this important family of transporters.