Intrinsically disordered proteins (IDP) challenge current views on biomolecular communication. These proteins participate in functional biological complexes despite their lack of 3D structures, a scenario which until recently was unimaginable. IDPs and large intrinsically disordered regions in otherwise folded proteins constitute 30-40% of the human proteome, but currently they represent a ‘dark matter’ that is hard to investigate with traditional methods.
Recent observations of extremely high-affinity disordered complexes (Kd in the pM-nM range), kinetics that evades established concepts (competition via transient ternary complexes), liquid-liquid phase separation, and novel disorder-driven allosteric mechanisms show an unanticipated biological and chemical versatility of IDPs. An important key to unlocking the enigmatic nature of IDPs is the development of appropriate experimental methods, mechanistic models, and a coherent conceptual framework.
In our research group at the Structural Biology and NMR laboratory at the Linderstrøm-Lang Centre for Protein Science, Department of Biology we study the structure, dynamics and functions of IDP and how intermolecular communication in modular protein is regulated by disorder. We use a wide-spanning interdisciplinary approach combining a range of specialized experimental techniques, including protein NMR spectroscopy, stopped-flow kinetics, CD, fluorescence, and ITC and collaborate with internationally recognized scientists working with detailed molecular dynamics simulations, single-molecule techniques, as well as cellular and whole organism methodologies. We seek to deliver deep mechanistic understanding and to take in-vitro studies into the cell to assess biological functions of IDPs.
Projects are available studying the function of disorder in transcription factors, membrane proteins and proteins relevant for neurodegenerative diseases. Depending on time, interest and prior competences, the exact protein systems will be decided on. If you have an IDP of your own particular interest, we are open to engage in discussions on projects relevant to this protein. You will learn how to design experiments, and acquire, analyze and discuss biophysical data relevant to the understanding of IDP functions, and will typically do so within a team of other students, PhD students and post docs with mutual interests.
Our research group joins people from across the world with expertise from a broad range of backgrounds including biochemistry, chemistry and molecular bioscience. Besides our international collaborations we work closely with colleagues at BIO.
Projects are available both at the BSc and MSc level and for ERASMUS students with a relevant biophysical background. For more information about the Linderstrøm-Lang Centre, SBiNLab and our research please have a look at:
Methods used and keywords: Proteins, intrinsically disordered proteins, IDP, NMR, biophysics, interactions, biochemistry, protein chemistry, transcription factors, membrane proteins, spectroscopy,
Keywords in Danish: biokemi, proteinkemi, proteiner, NMR, spektroskopi, biofysik, interaktioner, IDP, transkriptionsfaktorer, membranproteiner,
Contact person / supervisor:
Prof. Birthe B. Kragelund, firstname.lastname@example.org
Section for Biomolecular Sciences, Structural Biology and NMR Laboratory.