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My Chem/Biochem

  • Suf evolution

    Evolution of the Suf pathway

  • SufS

    The SufS cysteine desulfurase donates persulfide

  • SufC

    The SufC ATPase is the engine driving the SufBCD complex

  • SufBCD

    The SufBCD Fe-S cluster scaffold complex

    Two Hg ions (grey spheres) may indicate the Fe-S cluster binding site.

  • Fe-S cluster disruption

    Fe-S cluster biogenesis and stress

F. Wayne Outten Group Site

Research

We seek to understand the biochemical details of how the critical process of iron-sulfur (Fe-S) cluster biogenesis occurs in cells.  We also are discovering how cells regulate Fe-S cluster biogenesis in response to environmental changes that perturb Fe-S cluster demand (such as iron starvation and oxidative stress) or as part of metabolic reorganization due to changes in nutrient availability.

Fe-S cluster biogenesis

Currently the main project in our lab is the study of the Suf Fe-S cluster biogenesis system in bacteria.  This pathway is used in some bacterial pathogens for building Fe-S clusters under stress conditions, such as iron starvation or oxidative stress.  We are taking advantage of the versatile model organism, Escherichia coli (or E. coli) to study this pathway.  E. coli are gram-negative Proteobacteria that grow rapidly and can be genetically manipulated with a variety of techniques.  They make an ideal single cell model to study this process.  The E. coli Suf system consists of multiple proteins, most of which are encoded by the sufABCDSE operon.  Most recently we have focused our efforts on characterizing the individual Suf proteins in vitro using purified proteins.  We are studying how the proteins interact, the individual mechanistic roles of each protein in the Fe-S cluster assembly process, and how the proteins regulate each others activities to coordinate Fe-S cluster assembly.

Regulation of Fe-S cluster metabolism in pathogens

More recently we have initiated a new project to characterize how bacterial pathogens regulate Fe-S cluster metabolism, including Fe-S cluster biogenesis and utilization of Fe-S cluster metalloenzymes.  This question is important for understanding how bacterial pathogens survive during infection.  Many aspects of the human immune response are directed against bacterial iron homeostasis, including oxidative stress generated by human macrophages and iron sequestration during infection.  In turn, bacterial pathogens must be able to sense these attacks and respond to them by altering the expression of genes involved in iron and Fe-S cluster metabolism.  We are studying the SufR protein in Mycobacterium marinum, a BSL2 fish pathogen that shares many hallmarks of infection with the more serious Mycobacterium tuberculosis organism that causes TB.  Our hypothesis is that SufR coordinates the transcriptional regulation of the M. marinum suf operon (and possibly other genes) in response to conditions that perturb Fe-S cluster metabolism.  By understanding how this process works in the bacterium, we may be able to disrupt it during pathogenesis using novel therapeutic approaches.

dhhs

Current Funding: Fe-S cluster biogenesis

Our work on the Suf system is funded by the National Institutes of Health (NIH) via R01 grant GM 112919.

usc

Current Funding: Fe-S cluster regulation

Our new project on Fe-S cluster regulation is funded by the University of South Carolina Vice-President for Research.

 


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