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.

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:

• Aug 1, 2023: Nikolaj Zwergius starts his PhD position on "Studies on co-transcriptional folding of RNA nanostructures" in Andersen lab
• Mar 1, 2023: Aleksandra Maria Bednarz starts her Postdoc position on "Determination of folding kinetics parameters" in Birkedal lab
• Nov 1, 2022: Emil Laust Kristoffersens starts his Postdoc position on "Structural studies of RNA origami folding" in Andersen lab
• Sep 1, 2022: Johan Nygaard Vinter starts his PhD position on "Kinetic folding algorithms for RNA design" in Pedersen lab
• Aug 1, 2022: Sofie Thomsen starts her PhD position on "RNA folding studies using fluorescent aptamers" in Birkedal lab
• Jul 1, 2022: Kalinka Hansen starts her Research Assistant position in Andersen lab
• May 1, 2022: Adam Sidi Mabrouk starts his PhD position on "RNA origami as a tool for cell biology studies" in the Briegel lab
• Apr 15, 2022: PhD position in Birkedal lab posted
• Apr 15, 2022: PhD position in Andersen lab posted
• Mar 17, 2022: PhD position in Pedersen lab posted
• Feb 1, 2022: News item: Interdisciplinary team will elucidate the rules of RNA folding