Project Info

Designing new drugs to treat bacterial infections by inhibiting the iron-sulfur cluster biosynthetic pathway

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 that are present in different parts of the cell. One of these pathways is unique to bacteria and critical for their survival. In this project, the FeS cluster biosynthetic pathway in bacteria (the ‘SUF pathway’) 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 or Mycobacterium tuberculosis, for example.

More Information

1. Vernis, L.; El Banna, N.; Baille, D.; Hatem, E.; Heneman, A.; Huang, M.-E. “Fe-S Clusters Emerging as Targets of Therapeutic Drugs.” Oxidative Medicine and Cellular Longevity 2017, Article ID: 3647657.
2. 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.
3. 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.
4. Gisselberg, J. E.; Dellibovi-Ragheb, T. A.; Matthews, K. A.; Bosch, G.; Prigge, S. T. “The Suf Iron-Sulfur Cluster Synthesis Pathway is Required for Apicoplast Maintenance in Malaria Parasites.” PLOS Pathogens 2013, 9, e1003655.

Grand Engineering Challenge: Engineer better medicines

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

30-40 hours/month

Skills/Techniques Gained

Cell culture, protein purification, protein crystallography, organic synthesis, in vitro assays.

Mentoring Plan

The student will work closely with the PI and graduate students in the group for assistance with instrument/technique training, experimental design, and project direction. Initially, the student will be paired with a graduate student to learn the necessary techniques. As the student gains experience, he or she may operate with greater independence. This lab/project is new as of summer 2019; therefore, the student can expect to interact frequently with the PI and receive training directly from the PI (in addition to training/mentoring from graduate students).