Methods in Systems Bioinorganic Chemistry

Paul A. Lindahl has researched topics in the field of bioinorganic chemistry for nearly 50 years, and has seen its development and never-ending evolution. He obtained his PhD in chemistry from the Massachusetts Institute of Technology in 1985, and then moved to the University of Minnesota where he was a post-doctoral fellow in Eckard Münck’s lab. In 1988 he joined the faculty at Texas A&M University where he is currently Professor of Chemistry and of Biochemistry and Biophysics. He began his research in bioinorganic chemistry at the Illinois Institute of Technology as an undergraduate modeling the copper site in plastocyanin. After a year in graduate school at the University of California, Berkeley, he moved to MIT and joined the laboratory of William Orme-Johnson. There he studied the molybdenum-and-iron containing enzyme nitrogenase. During his post-doc, he used Mössbauer and EPR spectroscopies to study the nickel-and-iron containing bifunctional enzyme acetyl-coenzyme A synthase/carbon monoxide dehydrogenase, including how it interacts with a cobalt-and-iron containing protein. Thus, he has researched nearly all the transition metals used in nature. He continued to study this Ni-Fe-Co system for 2 decades at Texas A&M University, focusing on the mechanism of catalysis, including structural and spectroscopic aspects. In the late 1990’s he discovered that this enzyme was implicated in the iron-sulfur-world origin-of-life scenario proposed by Gunter Wächtershäuser, and this prompted a pivotal shift in his research towards metal metabolism in more complex cellular systems. In the past 2 decades, he has used the same biophysical methods that he used to study individual metalloenzymes to investigate metal metabolism in whole-cells and in subcellular structures such as mitochondria and cytosol. He also developed new bioanalytical methods by interfacing liquid chromatography with inductively-coupled plasma mass spectrometry to probe labile iron, copper, and zinc pools in various cellular systems, including their roles in cellular homeostatic regulation. He is currently using these tools to investigate the dysregulation of iron associated with hereditary hemochromatosis in mice (and by extension in humans). With the critical help of mathematicians, he has developed, and continues to develop, new approaches to quantitatively model iron and copper metabolism in eukaryotic cells using ordinary-differential equations. He looks forward to the day when these disparate approaches can be unified to clarify how biochemical processes are integrated within the human body to better understand metal-associated diseases.