GRK 2467:  Intrinsically Disordered Proteins – Molecular Principles, Cellular Functions, and Diseases

• Subject Area: Basic Research in Biology and Medicine
• Term: since 2019
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 391498659

In the last years, it has become apparent that a significant fraction of proteomes of both prokaryotes and eukaryotes is comprised of intrinsically disordered proteins (IDPs) or proteins containing intrinsically disordered regions (IDRs). These proteins lack a defined tertiary structure and often show a lower sequence complexity compared to folded proteins. Post-translational modifications are crucial for the biological functions of IDPs/IDRs enabling phase separation and membrane-less organelle formation. It is assumed that 50 to 60% of all eukaryotic proteins are intrinsically disordered or contain IDRs. In eukaryotes, 52 to 67% of all proteins are assumed to contain IDRs with a length of 40 or more amino acids. IDPs/IDRs seem to play an important role in membrane-associated processes and cell signaling. They are also important for the regulation of cell growth and are involved in cell differentiation and proliferation processes. Despite the ubiquitous involvement of IDPs/IDRs and their central importance for biological functions, the nature of their physiological relevance remains largely unexplored. In the RTG2467, various biochemical and biophysical techniques are available for characterizing the conformational ensembles of IDPs/IDRs. In the first funding period of the RTG2467, important insights were gained into the molecular principles underlying IDP/IDR functions. In the second funding period of the RTG2467, studying the importance of IDPs/IDRs in cellular systems and organisms will be in the focus. Cell-based methods will be strengthened to gain a better understanding of how IDPs/IDRs exert their functions in disease-related processes. After having characterized several IDPs/IDRs in the first funding period using mainly purified proteins via in vitro approaches, in cellulo and in vivo strategies will now be the focus of the second funding period. We aim to get important insights into the involvement of IDPs/IDRs regarding the development and progression of pathophysiological states. Close interactions of PIs of the RTG2467 with different scientific backgrounds in biophysics, biochemistry, and cell biology are a prerequisite for achieving a better understanding of the IDP/IDR contributions to cellular processes and (patho)physiology. The RTG2467 aims at addressing four main research questions: (i) Which molecular properties contribute to the conformational plasticity of IDPs/IDRs? (ii) How do these properties shape specific interactions of IDPs/IDRs with other proteins and nucleic acids? (iii) How do IDPs/IDRs influence molecular pathways in cellular systems and organisms? (iv) How do IDPs/IDRs contribute to the development and progression of pathophysiological states? The RTG2467 will build on its previous success as a consortium that is centered on IDP/IDR research and offers optimal training perspectives for young scientists.

• DFG Programme: Research Training Groups
• Applicant Institution: Martin-Luther-Universität Halle-Wittenberg
• Participating Institution: Leibniz-Institut für Pflanzenbiochemie (IPB)
• Spokesperson: Professorin Dr. Andrea Sinz
• Participating Researchers: Dr. Christian Arlt, since 2/2024; Professor Dr. Jochen Balbach; Professorin Dr. Katharina Bürstenbinder, until 11/2023; Professor Dr. Christian R. Eckmann; Professor Stephan-Michael Feller, Ph.D.; Professor Dr. Stefan Hüttelmaier; Professor Dr. Panagiotis L. Kastritis; Professorin Dr. Sonja Keßler; Dr. Marcel Köhn; Dr. Maria Ott; Professorin Dr. Tina Romeis; Professor Dr. Milton T. Stubbs