Improving heterologous protein production by tweaking transcript elements

Project

Improving heterologous protein production by tweaking transcript elements

This project aims to elucidate the complex relationship between codon usage, mRNA secondary structures and translational elements to create a reliable design for stable and high protein expression.

Optimization of protein production remains a trial and error approach mainly due to our lack of understanding what the key factors are in efficient translation. There is an intrinsic correlation between the mRNA sequence and secondary structures.  Synonymous mutations in the coding DNA sequence (CDS), for example introduced by codon harmonization/optimization, can improve translation efficiency. However, they may also create new inhibitory secondary structures that limit translation initiation or slow down the translation elongation process.

This project aims to develop a systematic approach to design and select transcripts for both prokaryotes and eukaryotes with consistent high expression levels, regardless of the CDS used.

  • Transcript elements will be individually designed and tested for interference capabilities, which will then be minimized.
  • Current and new optimization techniques for the CDS will be examined for several model proteins in different hosts.
  • New methods will be tested to analyse secondary structures in vivo.
  • Finally, all the obtained information will be encompassed in a predictive algorithm which will be developed concurrently with all the above-mentioned projects.

Thesis projects are available for enthusiastic and organized BSc and MSc students. If you have any questions regarding the projects and their availability, please do not hesitate to contact me.