Faculty of Arts & Science
Biochemistry

Email: hj.wieden@uleth.ca

Webpage: http://people.uleth.ca/~hj.wieden/

Research

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.

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.

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 the Laboratory for biomolecular design and engineering and contribute to the Laboratory for Synthetic Biology.

Selected Publications

Becker, M., Gzyl, K., Altamirano A.M., Vuong, A., Urban, K., Wieden, H.-J. (2012) The 70S ribosome modulates the ATPase activity of Escherichia coli YchF. RNA Biology 9(10): 1288-1301.

Fischer, J., Coatham, M.L., Eagle Bear, S., Brandon, H.E., De Laurentiis, E.I., Shields, M.J., Wieden, H.-J. (2012) The ribosome modulates the structural dynamics of the conserved GTPase HflX and triggers tight nucleotide binding. Biochimie 94(8):1647-1659. (IF: 3.02)

Delaurentiis, E.I., Mo, F., and Wieden, H.-J. (2011) Construction of a fully active Cys-less Elongation Factor Tu: Functional role of the conserved Cystein 81. Biochim. Biophys. Acta. 1814, 684-692. (IF: 3.64)

Wieden, H.-J., Mercier, E., Gray, J., Steed, B., Yawney, D. (2010) A combined molecular dynamics and rapid kinetics approach to identify conserved 3 dimensional communication networks in Elongation Factor Tu. Biophys J. 99, 3735-3743

Shields, M., Fischer, J., Wieden, H.-J. (2009) Toward understanding the function of the universally conserved GTPase HflX from Escherichia coli: A kinetic approach. Biochemistry 48, 10793-10802

Group Members (Current)

1. Dr. Tobias Schümmer (PDF)
2. Evan Mercier (PhD Student)
3. Evelina DeLaurentiis (PhD Student)
4. Kirsten Rossler (MSc Student)
5. Dylan Girodat (MSc Student)
6. Justin Vigar (MSc Student)
7. Luc Roberts (MSc Student)
8. Mackenzie Coatham (MSc Student)
9. Harland Brandon (MSc Student)
10. Fan Mo (Research Assistant)
11. Katherine Gzyl (Undergraduate, Honors Thesis)
12. Iain Barkley (Undergraduate)
13. Tom Guo (Undergraduate)
14. Quinn Daviduck (Undergraduate)
15. Dipankar Goyal (Undergraduate)
16. Quinn Storozynsky (Undergraduate)

Research Funding (Current)

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