Contact Information:
Department of Chemistry
Texas A&M University
College Station, TX 77842
Phone: (979) 845-0956
Fax: (979) 845-4719
lindahl@mail.chem.tamu.edu

Paul A Lindahl
Professor

Ph. D., Massachusetts Institute of Technology

Areas of Interest:

• Biophysical and Bioinorganic Chemistry
• Mechanistic Modeling of Biological Processes
• EPR and Mössbauer spectroscopy
• Systems Biology
• Cellular Iron Metabolism
• Anaerobic biochemistry

Lindahl Research Laboratory

CBI Program

One of our two current research areas involves iron metabolism in mitochondria. The iron imported into these organelles is assembled into iron-sulfur clusters and heme prosthetic groups. Some of these centers are exported into the cytosol, while others are installed into mitochondrial apo-proteins. All of these processes are regulated in healthy cells, but various genetic mutations giving rise to diseases can cause iron to accumulate (e.g. Friedreich's ataxia) or become depleted (e.g. Sideroblastic anemia). We have developed a biophysical approach involving Mössbauer, electron paramagnetic resonance, and electronic absorption spectroscopy, to study the entire iron content of intact mitochondria in healthy and genetically altered cells. This Systems Biology approach allows us to characterize the "iron-ome" of mitochondria at an unprecedented level of detail. We are also using analytical tools (e.g. liquid chromatography) to identify complexes that are involved in "trafficking" iron into and out of the organelle.

Our other research area involves mathematical modeling of cellular self-replication on the mechanistic biochemical level. We collaborate on this multidisciplinary NSF-sponsored project with a mathematician at the University of Houston (Professor Jeffrey Morgan). We have developed a modeling framework that facilitates such modeling efforts, and have designed a number of very simple and symbolic in silico cells that exhibit self-replicative behavior. Our minimal in silico cell model includes just 5 components and 5 reactions. A second generation model includes a more realistic mechanism of mitotic regulation. One novel aspect of our approach is that cellular concentration dynamics impact (and are impacted by) cellular geometry. By minimizing membrane bending energies, we are now calculating cell geometry during growth and division. Our results suggest that the "pinching" observed in real cells is enforced by cytoskeletal structures. Towards this end, we have modeled the assembly, steady-state dynamics, and contraction of the FtsZ ring found in prokaryotic cells. We are currently integrating this model within a whole-cell model to afford pinching behavior. Future studies will involve modeling the actomyosin ring that is used in animal cell cytokinesis. Students interested in this project should have good math and physical chemistry skills.

"Kinetic Modeling of the Assembly, Dynamic Steady State, and Contraction of the FtsZ Ring in Prokaryotic Cytokinesis" Ivan V. Surovtsev, Jeffrey J. Morgan, Paul A. Lindahl, Plos Computational Biology, 2008, In press.

"Electron paramagnetic resonance and Mössbauer spectroscopy of intact mitochondria from respiring Saccharomyces cerevisiae" Brandon Hudder, Jessica Garber Morales, Audria A. Stubna, Eckard Münck, Michael P. Hendrich, and Paul A. Lindahl, Journal of Biological Inorganic Chemistry 2007, 12, 1029-1053.

"Whole-cell modeling framework in which biochemical dynamics impact aspects of cellular geometry" Ivan V Surovtsev, Jeffrey J Morgan and Paul A Lindahl, Journal of Theoretical Biology, 2007, 244, 154-166.

"A Framework for Whole-Cell Mathematical Modeling" Jeffrey J. Morgan, Ivan V. Surovtsev, and Paul A. Lindahl, Journal of Theoretical Biology 2004, 231, 581-596.

"Mössbauer Evidence for an Exchange-Coupled {[Fe₄S₄]¹⁺:Nip¹⁺} A-cluster in Isolated Alpha Subunits of Acetyl-Coenzyme A Synthase/Carbon Monoxide Dehydrogenase" Xiangshi Tan, Marlène Martinho, Audria Stubna, Paul A. Lindahl, and Eckard Münck, Journal of the American Chemical Society 2008, 130, 6712-6713.

"Tunnel Mutagenesis and Ni-dependent Reduction and Methylation of the Alpha Subunit of Acetyl-Coenzyme A Synthase/Carbon Monoxide Dehydrogenase" Xiangshi Tan and Paul A. Lindahl, 2008, J. Biol. Inorg. Chem. 13, 771-778.

"Nickel-dependent oligomerization of the alpha subunit of acetyl-coenzyme a synthase/carbon monoxide dehydrogenase" Xiangshi Tan, Ioannis Kagiampakis, Ivan Surovtsev, Borries Demeler and Paul A. Lindahl, Biochemistry 2007, 46, 11606-11613

"Function of the Tunnel in Acetyl-Coenzyme A Synthase/Carbon Monoxide Dehydrogenase" Xiangshi Tan, Anne Volbeda, Juan C. Fontecilla-Camps, and Paul A. Lindahl, Journal of Biological Inorganic Chemistry, 2006, 11, 371-378.

"Mössbauer and EPR Study of Recombinant Acetyl-CoA Synthase from Moorella thermoacetica" Matthew R. Bramlett, Audria Stubna, Xiangshi Tan, Ivan V. Surovtsev, Eckard Münck and Paul A. Lindahl, Biochemistry, 2006, 45, 8674-8685.

"Kinetics of CO Insertion and Acetyl Group Transfer Steps, and a Model of the Acetyl-CoA Synthase Catalytic Mechanism" Xiangshi Tan, Ivan V. Surovtsev and Paul A. Lindahl Journal of the American Chemical Society 2006, 128, 12331-12338.

"Ni-Zn-[Fe4S4] and Ni-Ni-[Fe4S4] Clusters in Closed and Open Subunits of Acetyl-CoA Synthase/Carbon Monoxide Dehydrogenase" Claudine Darnault, Anne Volbeda, Eun Jin Kim, P. Legrand, Xavier Vernede, Paul A. Lindahl, and Juan C. Fontecilla-Camps, Nature Structural Biology, 2003, 10, 271-279.