[ccp4bb] Postdoctoral positions available

[Barondeau, David P]

Postdoctoral positions are available immediately in the Barondeau lab at Texas 
A 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
https://www-ssrl.slac.stanford.edu/content/science/highlight/2017-09-30/structure-human-cysteinedesulfurase-complex

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:
https://tamus.wd1.myworkdayjobs.com/en-US/TAMU_External/job/College-Station-TAMU/Postdoctoral-Research-Associate-1_R-000735

Please also feel free to contact me at 
barond...@tamu.edu for more information.


-
David P. Barondeau
Associate Professor
Department of Chemistry
Texas A University
301 Old College Main
College Station, TX 77843
Office: ILSB 1196A
Phone: (979) 458-0735
http://www.chem.tamu.edu/rgroup/barondeau/

[ccp4bb] Postdoctoral and PhD positions

[Barondeau, David P]

Postdoctoral and PhD positions in the Barondeau lab available in the areas of 
bioinorganic and biophysical chemistry.

For more details see
https://www.chem.tamu.edu/rgroup/barondeau/website/documents/Barondeau-lab-postdoc-PhD-positions.pdf


-
David P. Barondeau
Associate Professor
Department of Chemistry
Texas A University
301 Old College Main
College Station, TX 77843
Office: ILSB 1196A
Phone: (979) 458-0735
http://www.chem.tamu.edu/rgroup/barondeau/

[ccp4bb] Postdoctoral positions available

[Barondeau, David P]

Dear all,

   We are looking to fill postdoctoral positions in my lab.  See below.

Postdoctoral positions in the Barondeau lab at Texas A University Department 
of Chemistry are available immediately for highly motivated, creative 
individuals with a strong interest in biophysical and/or bioinorganic 
chemistry. Our labs are located in the Interdisciplinary Life Sciences building 
(http://vpr.tamu.edu/resources/ilsb), where we have access to state-of-the-art 
facilities for structural biology, mass spectrometry, and enzymology.

Our group is focused on understanding metallocofactor assembly and the 
functional tuning partnership between metallocofactors and their protein 
environments.

Project 1.  Structure-function studies of the human Fe-S assembly complex. This 
project combines recombinant DNA methods with enzymology, chemical biology, and 
structural methods and is funded by the NIH (renewed in 2017). We recently 
reported crystal and EM structures along with functional properties of the 
mitochondrial cysteine desulfurase (NFS1-ISD11-ACP) complex 
(https://www.ncbi.nlm.nih.gov/pubmed/28634302).
Highlights of our study:

  *   http://www.science.tamu.edu/news/story.php?story_ID=1812#.WUlPlmjyuUl
  *   
https://f1000.com/prime/article?articleId=727738370_medium=email_source=ts
  *   
https://www-ssrl.slac.stanford.edu/content/science/highlight/2017-09-30/structure-human-cysteine-desulfurase-complex

We report lock-and-key or anchoring interactions between the acyl-chain of ACP 
and ISD11 (a member of the eukaryotic-specific LYRM protein superfamily) along 
with a novel cysteine desulfurase architecture. This core cysteine desulfurase 
complex also binds three additional proteins, including the Friedreich's ataxia 
protein frataxin, to generate the fully functional Fe-S cluster assembly 
complex. Our objectives are to elucidate structural properties for how these 
additional proteins bind to the core complex and provide mechanistic details of 
how allosteric protein interactions, lipid binding, and post-translational 
modifications modulate Fe-S cluster biosynthesis.

Project 2. Fluorophore labeling and kinetic interrogation of Fe-S assembly 
pathways. This project (funded by the NSF) combines chemical biology, 
fluorescent plate reader and circular dichroism based assays and global fit 
kinetic analysis to elucidate the function of proteins in bacterial Fe-S 
assembly and transfer pathways. We have previously reported an intein-based 
approach to fluorophore label Fe-S proteins with rhodamine and then use 
fluorescence to monitor cluster content. This approach has the advantage of 
only monitoring Fe-S clusters bound to the protein or protein complex that is 
labeled with the fluorophore. For additional information see 
http://pubs.acs.org/doi/10.1021/ja510998s and 
http://pubs.acs.org/doi/abs/10.1021/acschembio.6b00632. Our objectives are to 
test the proposed roles of iron donor, activator/inhibitor, chaperone, 
intermediate carrier and cluster conversion proteins as well as evaluate 
kinetic vs thermodynamic control in transfer and regulatory pathways.

Contact Dr. David Barondeau (barond...@tamu.edu) for 
additional details.
To apply for a position, please submit a brief description of research 
interests, career goals, CV, and contact information for three references.



-
David P. Barondeau
Associate Professor
Department of Chemistry
Texas A University
301 Old College Main
College Station, TX 77843
Office: ILSB 1196A
Phone: (979) 458-0735
http://www.chem.tamu.edu/rgroup/barondeau/