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Postdoctoral positions are available immediately in the Barondeau lab at Texas A&M University investigating structure-function properties of the mitochondrial iron-sulfur cluster biosynthetic complex. This project has components of structural
biology, bioinorganic chemistry, enzymology, and chemical biology.
https://www.chem.tamu.edu/rgroup/barondeau/website/documents/Barondeau-lab-postdoc-PhD-positions.pdf
The project is funded by NIH (renewed in 2017) and focuses on structure-function properties of the human Fe-S cluster assembly complex. Fe-S clusters are ancient protein cofactors that are required for some of the most important reactions
in biology. Conserved biosynthetic pathways build and distribute these clusters to the hundreds, if not thousands, of proteins that require Fe-S clusters for their function. In humans, an Fe-S assembly complex located in the mitochondrial matrix is responsible
for synthesizing Fe-S clusters. Defects in the biogenesis of iron-sulfur clusters are directly associated with myopathy, neurodegenerative ataxia and ataxia-susceptibility, and contribute to genomic instability, the development of cancer, and aging. The structural
core of this assembly complex consists of cysteine desulfurase (NFS1), eukaryotic-specific LYR protein (ISD11), and acyl carrier protein (ACP) subunits and is referred to as the SDA complex. We recently reported crystal and electron microscopy structures along
with functional properties of the mitochondrial cysteine desulfurase (NFS1-ISD11-ACP) complex (https://www.ncbi.nlm.nih.gov/pubmed/28634302). This manuscript describes lock-and-key interactions between
the acyl-chain of ACP and ISD11 along with a novel cysteine desulfurase architecture.
Highlights of this study:
http://www.science.tamu.edu/news/story.php?story_ID=1812#.WUlPlmjyuUl
Objectives of the project
1. Apply biophysical methods (X-ray crystallography, SAXS, EM, and mass spectrometry based methods) to determine the interactions between the three accessory proteins and the core SDA complex that constitute the fully functional Fe-S
cluster assembly complex.
2. Elucidate the determinants that drive quaternary structure and activity differences between NFS1 and its prokaryotic homolog IscS.
3. Explore how the composition of the acyl-chain associated with ACP and post-translational modifications influence the structure of the assembly complex and its ability to synthesize Fe-S clusters.
4. Determine molecular details of the frataxin activation mechanism for Fe-S cluster biosynthesis as a step towards a treatment for Friedreich’s ataxia.
5. Investigate the roles of individual proteins in Fe-S cluster assembly and distribution networks using a chemical biology approach coupled to global fit kinetic analysis. This strategy takes advantage of an intein-based strategy
to incorporate fluorophore labels that can be used to report cluster content (http://pubs.acs.org/doi/10.1021/ja510998s).
To apply for a Postdoctoral position (initial application deadline February 1st, 2018), see link below:
Please also feel free to contact me at
[log in to unmask] for more information.
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David P. Barondeau
Associate Professor
Department of Chemistry
Texas A&M University
301 Old College Main
College Station, TX 77843
Office: ILSB 1196A
Phone: (979) 458-0735
http://www.chem.tamu.edu/rgroup/barondeau/