Dennis R. Dean

DISTINGUISED PROFESSOR
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Dennis R. Dean is a professor of Biochemistry in the College of Agricultural and Life Sciences and has been a member of the Virginia Tech faculty for 38 years.  He attended Wabash College (B.A. 1973) and is a Purdue University College of Science Distinguished alumnus (Ph.D. 1979).  He was an NIH Post-Doctoral Fellow at the University of Wisconsin and a Staff Scientist at the Kettering Research Laboratory before joining the Virginia Tech faculty in 1985.  He was the founding director of the Fralin Life Sciences Institute and holds the title of University Distinguished Professor. He served as the term director for both the Virginia Tech Carilion Research Institute, recently renamed the Fralin Biomedical Research Institute, the Virginia Bioinformatics Institute and as the Virginia Tech Vice President for Research and Innovation. He has served on the editorial board of the Journal of Biological Chemistry, the publications board of the American Society for Biochemistry and Molecular Biology and the editorial board of the Journal of Bacteriology and is currently a member of the ethics committee for the American Society for Microbiology. He is a fellow of the American Academy of Microbiology, the American Academy for the Advancement of Science, the American Society for Biochemistry & Molecular Biology and the Virginia Academy of Science, Engineering & Medicine. Dr. Dean’s research interests involve the biological mechanism for formation of simple and complex [Fe-S] cluster-containing enzymes and their role in the activation of the catalytic component of biological nitrogen fixation. His laboratory group has published over 200 articles on that topic.

PHONE NUMBER
+1 (540) 231-5895
EMAIL ADDRESS
deandr@vt.edu
The goal of the Biological Nitrogen Fixation in Cereals (BNF Cereals) project is to engineer varieties of cereals that require little or no input of chemically synthesized nitrogen fertilizers. This goal will be achieved by transferring bacterial nitrogenase genes to the plant thus enabling nitrogen acquisition from the atmosphere rather than from synthetic fertilizers.

Biography

During his doctoral studies at Purdue University Dr. Dean explored genetic and biochemical aspects of nitrogen assimilation in the gram-negative bacterium Bacillus subtilis. These studies revealed that mutations disabling the catalytic activity of glutamine synthetase resulted in the elevated production of the enzyme indicating an autoregulatory expression mechanism. As an NIH post-doctoral fellow in the laboratory of Masayasu Nomura at the University of Wisconsin Dr. Dean was part of a collaborative research group that discovered a translational feedback regulatory mechanism in Escherichia coli that controls the balance and coordinate expression of ribosomal proteins. During the past 40 years as an independent scientist work in the Dean laboratory has focused on the genetic analysis of biological nitrogen fixation in the free-living nitrogen-fixing bacterium Azotobacter vinelandii with particular emphasis on the maturation of the catalytic components involved in catalysis. Among his most significant scientific contributions are included discovery of the primary biological machinery necessary for formation of simple and complex [Fe-S] clusters in bacteria, the role of molecular scaffolds in that process, and the mechanism for sulfur activation and trafficking in bacterial cells.  These discoveries were important because they answered a basic question concerning how the otherwise highly toxic elements Fe and S can be combined to form redox-active [Fe-S] clusters necessary to sustain many essential cellular functions.  Among these cellular functions are included nitrogen fixation, photosynthesis, and respiration.  The mechanism for S activation and trafficking for [Fe-S] cluster assembly discovered in the Dean laboratory is now known to be a nearly universal process that provides the sulfur necessary for formation of most S-containing biomolecules, including tRNA, thiamine, and biotin. There are practical biotechnological opportunities associated with this emergent field because [Fe-S] cluster-containing enzymes, such as nitrogenase, sustain life on earth. As a member of a consortium of scientists Dean and his collaborators were able to establish that a key feature of the activation of N2 for biological nitrogen fixation involves a reductive elimination mechanism that explains the requirement of one H2 evolved for each N2 reduced. More recently the nitrogenase research consortium has explored the role of a central carbon atom located within the cofactor that provides the nitrogenase active site. These studies revealed that the central carbon plays an import role in stabilizing the cofactor structure rather than directly contributing to catalysis.

Research Areas
Program Focus

Research in the laboratory of Dennis Dean is focused on two principal themes: the mechanism for biological nitrogen fixation and the biological pathways for assembly of simple and complex metalloclusters.  With respect to nitrogen fixation, his group developed a combined biochemical-genetic approach to identify where substrates interact with nitrogenase, the biological catalyst of nitrogen fixation.  This work enabled a series of biophysical approaches leading to the development of a comprehensive model for how certain substrates interact with the nitrogenase active site.

Achievements

Very recently his laboratory, in collaboration with Lance Seefeldt at Utah State University, used a genetic approach to remodel nitrogenase such that it has the capacity to reduce carbon dioxide to yield methane and various short-chain high-value olefins.  This finding suggests that the nitrogenase mechanism could provide clues for the rational development of metal-based catalysts for carbon dioxide sequestration.

The second theme has involved investigations on the biological assembly of iron-sulfur clusters.  These simple inorganic structures are perhaps nature’s most ancient prosthetic group and are likely to have contributed to the emergence of life on earth.  Dennis Dean’s laboratory discovered the biological mechanism for the assembly of iron-sulfur clusters and introduced the concept that both simple and complex iron-sulfur-containing prosthetic groups are pre-assembled on molecular scaffolds. Both in vitro and in vivo approaches have been used to establish the validity of the scaffold hypothesis.  Both the mechanism of sulfur trafficking and the role of scaffolds in metallocluster assembly have now been established as nearly universal biological processes.  Recent progress in this area has involved a collaborative project with Juan Fontecilla’s group in Grenoble to elucidate the crystallographic structure of an iron-sulfur cluster biosynthetic complex captured in the process of cluster assembly.  Ongoing work involves a comprehensive whole-genome transcriptome analysis of bacterial strains that are defective in various aspects of iron-sulfur assembly with the goal of understanding how this process is integrated with and contributes to intermediary metabolism.

Latest Publications
A conformational role for NifW in the maturation of molybdenum nitrogenase P-cluster

Chem. Sci., 2022,13:3489-3500
2022  |  Journal article
DOI: 10.1039/D1SC06418E
CONTRIBUTORS: Van Stappen, C., Jimenez-Vicente E., Pérez-González, A, Yang,Z.Y., Seefeldt, L.C., DeBeer, S., Dean, D.R., and L. DeCamps

AnfO controls fidelity of nitrogenase FeFe protein maturtion by preventing misincorporation of FeV-cofactor

Mol Microbiol. 2022 May;117(5):1080-1088
2022  |  Journal article
DOI: 10.1111/mmi.14890. Epub 2022 Mar 9
CONTRIBUTORS: Pérez-González, A., Jimenez-Vicente, E., Salinero-Lanzarote, A., Harris, D.F., Seefeldt, L.C., and D.R. Dean

Specificity of NifEN and VnfEN for the assemby of nitrogenase active site cofactors in Azotobacter vinelandii

mBio, 12(4)
2021  |  Journal article
DOI: 10.1128/mBio.01568-21
CONTRIBUTORS: Pérez-González, A., Jimenez-Vicente, E., Gies-Elterlein, J., Salinero-Lanzarote, A., Yang, Z.Y., Einsle, O., Seefeldt, L.C. and D.R. Dean

Selected Awards

2024

2022

Fellow of the American Society for Biochemistry & Molecular Biology

2021

Fellow of the Virginia Academy of Science, Engineering & Medicine

2012

Fellow of the American Association for the Advancement of Science

2010

Fellow of the American Academy of Microbiology

2009

University Distinguished Professor

2005

Stroobants Professor of Biotechnology

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Experience

2024

2015 — 2016

Virginia Tech Vice President for Research & Innovation

2012 — 2014

Director of Virginia Bioinformatics Institute

2008 — 2020

Director, Fralin Life Sciences Institute

2008 — 2010

Term Director, Virginia Tech Carilion Research Institute

2007 — 2020

Stroobants Professor of Biotechnology

2006 — 2008

Term Director, Institute for Biomedical & Public Health Sciences

2002 — 2008

Director, Fralin Biotechnology Center

1995 — 2002

Associate Director, Fralin Biotechnology Center

1994 — present

Professor, Department of Biochemistry

1988 — 1994

Associate Professor, Department of Anaerobic Microbiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia

1985 — 1988

Assistant Professor, Department of Anaerobic Microbiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia

1982 — 1985

Staff Scientist, Charles F. Kettering Research Laboratory, Yellow Springs, Ohio

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Education

Diplomas and degrees

Bachelor of Arts
Wabash College, Crawfordsville, Indiana, USA
Date of qualification: 1973

Doctorates

Ph.D. in Molecular Biology
Purdue University, West Lafayette, Indiana, USA
Date of qualification: 1979

 

NIH Postdoctoral Fellow
The University of Wisconsin, Madison, Wisconsin, USA
Date of qualification: 1979