SFB 1551:  Polymer Concepts in Cellular Function

Subject Area Biology
Chemistry
Physics
Term since 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 464588647
 

Project Description

According to the traditional view of molecular biology, DNA provides a library of information, RNA serves as a delivery agent, and proteins translated from RNA are the machines that perform various functions owing to their ingeniously folded structures. However, we now know that RNA and DNA not only store information sequentially, but also contribute to other functions in the cell through their physical nature as long, flexible, charged molecules (polyelectrolytes). For proteins, the recent "resolution revolution" in cryo-electron tomography and recent advances in artificial intelligence computing have ushered molecular biology into a new era in which structure–function relationships can be visualized with an unprecedented level of detail. However, about 30% of the proteome (all proteins in a cell) is intrinsically disordered, which refers to parts of proteins or entire proteins that are not folded, lack specific structure in their native states and evade such state-of-the-art analysis. Like RNA and DNA, intrinsically disordered proteins are essentially linear macromolecules with a high degree of conformational disorder but with distinct chemistry (typically with mixed charges forming a polyampholyte). For all these different macromolecules, it is clear that their polymeric character plays a crucial role in determining their functions inside living cells. In this Collaborative Research Centre, 16 interdisciplinary teams, each composed of at least one life scientist and one polymer scientist, will investigate how the polymeric character of DNA, RNA and disordered proteins, and the sum of their intramolecular and intermolecular interactions, gives rise to biological organization and cellular functions. This will challenge the molecular life scientists to reconsider cell and molecular biology processes from an unconventional perspective, and will require the polymer scientists to develop novel concepts for problems that are traditionally not part of materials and classical polymer science. The principal bio-macromolecules (DNA, RNA, proteins) will all be considered so as to reveal the general principles and commonalities of polymers across different length scales and chemistries. In particular, we will focus on DNA–protein assemblies in chromatin topology and regulation of transcription, and on RNA–protein complexes in splicing, translation regulation and small-RNA pathways. We will also study the multifaceted functions that proteins can perform as single molecules and also as nanoscopic and large ensembles, and how disruption of polymeric interactions can lead to cellular malfunctions. Our ultimate vision is a conceptual framework for the non-equilibrium description of multi-component cellular processes driven by the interplay of biopolymers. This will fill a void in our current understanding of cellular function and make this CRC a unique bilateral platform for exchange between the molecular life sciences and the polymer sciences.
DFG Programme Collaborative Research Centres

Current projects

Applicant Institution Johannes Gutenberg-Universität Mainz
Participating Institution Max-Planck-Institut für Biophysik; Max-Planck-Institut für Polymerforschung
Participating University Universität Stuttgart
Spokesperson Professor Dr. Edward A. Lemke