Project Info
Understanding and inhibiting the pathway of iron-sulfur cluster biosynthesis in pathogenic bacteria
Christine Morrison
morrison@mines.edu
Project Goals and Description:
Iron-sulfur (FeS) clusters are ubiquitous in biology and are critical for many biological processes, such as electron transfer. FeS clusters form in a variety of sizes and shapes, including 2Fe-2S and 4Fe-4S clusters as well as larger clusters. These clusters are formed in several FeS cluster machineries, such as the ISC, CIA, NIF, and SUF pathways. The SUF pathway is unique to some bacteria and critical for their survival. In this project, the FeS cluster biosynthetic pathway in bacteria will be investigated as a potential target for new drug development. Drugs against this pathway could be used to treat infections caused by Staphylococcus aureus, for example.
More Information:
Grand Challenge: Engineer better medicines.
- Blahut, M.; Sanchez, E.; Fisher, C. E.; Outten, F. W. “Fe-S Cluster Biogenesis by the Bacterial SUF pathway.” Biophys. Acta Mol. Cell Res. 2020, 1876, 18829. DOI: 10.1016/j.bbamcr.2020.118829.
- Selbach, B.; Earles, E.; Dos Santos, P. C. “Kinetic Analysis of the Bisubstrate Cysteine Desulfurase SufS from Bacillus subtilis.” Biochemistry 2010, 49, 8794-8802. DOI: 10.1021/bi101358k.
- Perard, J.; de Choudens, S. O. “Iron-Sulfur Clusters Biogenesis by the SUF Machinery: Close to the Molecular Mechanism Understanding.” Journal of Biological Inorganic Chemistry 2018, 23, 581-596.
- Dutter, B. F.; Mike, L. A.; Reid, P. R.; Chong, K. M.; Ramos-Hunter, S. J.; Skaar, E. P.; Sulikowski, G. A. “Decoupling Activation of Heme Biosynthesis from Anaerobic Toxicity in a Molecule Active in Staphylococcus aureus.” ACS Chemical Biology 2016, 11, 1354-1361.
Primary Contacts:
Christine Morrison, morrison@mines.edu
Student Preparation
Qualifications
Experience with cell cultures, protein purification, and/or in vitro assays would be helpful but is not required. The student should have an interest in biochemistry and chemistry.
TIME COMMITMENT (HRS/WK)
10-12
SKILLS/TECHNIQUES GAINED
Cell culture, protein purification, in vitro assays and protein characterization
MENTORING PLAN
The student will work very closely with a graduate student in the Morrison group for learning instrument/technique training, experimental design, and project direction. As the student gains experience, they may operate in the lab with greater independence, but they will always be able to access grad students or Dr. Morrison as questions arise. After receiving initial training in key lab techniques and is comfortable in the lab, the student is expected to work on their own independent project that may be published. The student’s experiments and project development will be supervised by the grad student and PI.
PREFERRED STUDENT STATUS
Freshman
Sophomore
Junior
Senior