Wieden Group

Email: hj.wieden@uleth.ca

Research

Synthetic Biology

Synthetic biology focuses on the rational design of biological systems using a multidisciplinary approach bridging classical molecular biology method and sophisticated bioinformatics and systems biology approaches. Our work focuses on the development of novel engineered expression platforms enabling innovative application addressing environmental and medical issues as well biotechnology.

Within the Alberta RNA Research and Training Institute (ARRTI), we belong to the Laboratory for biomolecular design and engineering and contribute to the Laboratory for Synthetic Biology.

Molecular Dynamics of Elongation Factors

Biomolecules such as Proteins and RNAs are intrinsically flexible, and typically undergo a wide variety of motions at normal temperatures. X-rays crystallographic structures as well as Cryoelectron microscopic studies of these biomolecules demonstrated that a high degree of conformational flexibility is important for the function. The flexibility and dynamics of proteins such as elongation factors has been optimized by evolution for their activities and functions. In order to analyze the role of the dynamical properties on their function, and to bridge the gap between the static structural data and the huge amount of biochemical and kinetic information that is available, the conformational flexibility of elongation factors such as EF-Tu and EF-G is studied using computational methods such molecular dynamics simulation in conjunction with advanced biophysical approaches including single molecule methods.

Molecular Mechanism of Antibiotics

With the steady emergence and spread of antibiotic resistant pathogens, the development of new antibiotics is increasingly important. We study the molecular mechanisms of antibiotic function using a multidisciplinary approach based on advance biophysical methods in order to provide a framework for the development of novel antimicrobial strategies. Our research focuses on antibiotics that target the cellular machinery of the pathogen that is responsible for translating genetic information into functional proteins, a process called translation. The detailed understanding of the involved processes is of fundamental importance for the development of new types of antibiotics. We study the molecular requirements for the inhibition of translation and analyze how resistance mechanisms work. On going research contributes to the development of novel tests that will allow us to search for chemical compounds that will effectively inhibit translation.

Selected Publications

  • Girodat, D., Mercier, E., Gzyl, K.E., and Wieden, H.-J.* (2019) Elongation Factor Tu’s Nucleotide Binding is Governed by a Thermodynamic Landscape Unique Among Bacterial Translation Factors. J. Am. Chem. Soc. 141(26): 10236-10246. DOI: 10.1021/jacs.9b01522 (IF: 14.357)
  • Sheahan, T., Hakstol, R., Kailasam, S., Glaister, G.D., Hudson, A.J., and Wieden, H.-J.* (2019) Rapid metagenomics analysis of EMS vehicles for monitoring pathogen load using nanopore DNA sequencing. PLoS One 14(7): e0219961. DOI: 10.1371/journal.pone.0219961 (IF: 2.776)
  • Smith, D.D., Girodat, D.,Wieden, H.-J.* and Selinger, L.B.* (2017) Streamlined purification of fluorescently labeled Escherichia coli phosphate-binding protein (PhoS) suitable for rapid-kinetics applications. Anal. Biochem. 537: 106-113. DOI: 10.1016/j.ab.2017.09.012 (IF: 2.219)
  • Dubé, S., Orr, D., Dempsey, B., and Wieden, H.-J.* (2017) A Synthetic Biology Approach to Integrative High School STEM Training. Nature Biotechnol. 35: 591-595. DOI: 10.1038/nbt.3896 (IF: 43.113)
  • Chao, Y., Li, L., Girodat, D., Förstner, K.U., Said, N., Corcoran, C., Śmiga, M., Papenfort, K., Reinhardt, R., Wieden, H.-J., Luisi, B., and Vogel, J.* (2017) A global in vivo cleavage map reveals a central role for RNase E in small RNA biogenesis. Mol. Cell. 65(1): 39-51. DOI: 10.1016/j.molcel.2016.11.002 (IF: 13.958)

Group Members (Fall 2019)

  1. Dr. Preethi Balasundaram (PDF)
  2. Fan Mo (Laboratory Manager)
  3. Harland Brandon (PhD Student)
  4. Luc Roberts (PhD Student)
  5. Taylor Sheahan (PhD Student)
  6. Dora Capatos (PhD Student)
  7. Dustin Smith (PhD Student)
  8. Davinder Kaur (PhD Student)
  9. Syndee Calhoun (MSc Student)
  10. Kristi Turton (MSc Student)
  11. Fabian Rhoden (MSc Student)
  12. Josh Friesen (Undergraduate)
  13. Josh King (Undergraduate)
  14. Justin Vigar (Research Technician)
  15. Jalyce Heller (Research Technician)
  16. Emily Wilton (Scientific Assistant)

Research Funding (Current)

NSERC, Canada Foundation for Innovation, CIHR, and Alberta Innovates Technology Futures