Project Info
Inhibiting and Activating an Essential Enzyme in S. aureus
Christine Morrison
morrison@mines.edu
Project Goals and Description:
This research aims to elucidate the fundamental biochemistry of inhibition and activation of an essential cysteine desulfurase in Staphylococcus aureus using chemical probes. The enzyme, called SufS, catalyzes sulfur acquisition in the sulfur mobilization (SUF) pathway, which is required to assemble essential iron-sulfur (Fe-S) clusters in bacteria. The SUF pathway is one of several pathways of Fe-S cluster biosynthesis, which are evolutionarily conserved throughout the kingdoms of life. Some organisms, including S. aureus, other Gram-positive bacteria, and some parasites, are unique in that they exclusively rely on the SUF pathway because they lack redundant Fe-S cluster machinery. Therefore, the SUF pathway is essential in these organisms. This provides an opportunity to explore how to modulate this pathway in a simpler system and investigate the impacts of modulation on cell survivability and iron homeostasis.
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.
Hudspeth, J. D.; Boncella, A. E.; Sabo, E. T.; Andrews, T.; Boyd, J. M.; Morrison, C. N.* “Structural and Biochemical Characterization of Staphylococcus aureus Cysteine Desulfurase Complex SufSU.” ACS Omega 2022, 7, 44124-44133. DOI: 10.1021/acsomega.2c05576. (Highlighted by Mines Newsroom: https://www.minesnewsroom.com/news/mines-researchers-explore-structure-staph-bacteria-develop-new-treatment-options)
Primary Contacts:
Christine Morrison (PI), <a href="mailto:morrison@mines.edu">morrison@mines.edu</a>
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, crystallography, computational modeling, 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