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COFOLD

Project name:

COFOLD - Co-transcriptional folding for RNA medicine and synthetic biology

Project period:

1 Feb 2022 – 31 Jan 2026

Grant:

The consortium, COFOLD, has received DKK 15 million from the Novo Nordisk Foundation through the Interdisciplinary Synergy Programme.

Brief summary:

One of the great scientific questions of molecular biology is how RNA and protein molecules fold into their final functional shapes. Even though some progress has been made, we are still very far from being able to predict the folding of complex molecular machines such as the ribosome, and even farther from being able to rationally design similar structures. In the COFOLD project we will study how RNA molecules fold during synthesis (co-transcriptional folding) using rational design of RNA folding pathways (RNA origami) as a key tool to gain detailed insight into this process. Cryo-electron microscopy will be used to characterize the 3-dimensional structure of co-transcriptional folding products and single-molecule fluorescence microscopy will be used to determine core kinetic parameters of folding events. Folding in cells will be investigated by cryo-electron tomography and fluorescence microscopy. The resulting insights will be used to improve RNA design algorithms and computer-aided design software to reliably predict and design co-transcriptional folding. Improved predictions of RNA folding in space and time will lead to a better understanding of the complex RNA assemblies found in biology and to an extraordinary ability to design functional RNAs, which will be of great importance for both medicine and synthetic biology.

Open positions:

Research projects:

  • WP 1: Develop algorithms for design of co-transcriptional folding (CSP lead).
    • PhD project: Kinetic folding algorithms for RNA design (CSP/ESA)
  • WP 2: Determine kinetic parameters of co-transcriptional folding (VB lead).
    • Postdoc project: Determination of folding kinetics parameters (VB/CSP)  
    • PhD project: RNA folding studies using fluorescent aptamers (VB/ESA)  
  • WP 3: Structural characterization of co-transcriptional folding products (ESA lead).
    • Postdoc project: Structural studies of RNA origami folding (ESA/AB)
    • PhD project: Development of novel RNA devices based on kinetic trapping (ESA/VB).
  • WP 4: Intracellular characterization of RNA structures and sensing devices (AB lead).
    • PhD project: RNA origami as a tool for cell biology studies (AB/VB).

News about project:

The consortium

  • Ebbe Sloth Andersen, Associate Professor, Interdisciplinary Nanoscience Center and Department of Molecular Biology and Genetics, Aarhus University.
  • Victoria Birkedal, Associate Professor, Department of Chemistry and Interdisciplinary Nanoscience Center, Aarhus University.
  • Christian Storm Pedersen, Associate Professor and Director of the Bioinformatic Research Center (BiRC), Aarhus University.
  • Ariane Briegel, Professor of Ultrastructural biology, Co-director of The Netherlands Centre for Electron Nanoscopy (NeCEN), Leiden University, Netherlands.