- Undergraduate Education
- B.A. North Park College, Chicago (1979)
- Graduate Education
- Ph.D. Massachusetts Institute of Technology (1985)
- Postdoc. University of Minnesota (1985-88)
- Joined Texas A&M in 1988
Cellular Iron Metabolism
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.
Nguyen, TQ, Dziuba, N, Lindahl, PA. Isolated Saccharomyces cerevisiae vacuoles contain low-molecular-mass transition-metal polyphosphate complexes. Metallomics. 2019; :.
Wofford, JD, Lindahl, PA. A mathematical model of iron import and trafficking in wild-type and Mrs3/4ΔΔ yeast cells. BMC Syst Biol. 2019;13 (1):23.
Wofford, JD, Bolaji, N, Dziuba, N, Outten, FW, Lindahl, PA. Evidence that a respiratory shield in Escherichia coli protects a low-molecular-mass FeII pool from O2-dependent oxidation. J. Biol. Chem. 2019;294 (1):50-62.
Dziuba, N, Hardy, J, Lindahl, PA. Low-molecular-mass iron in healthy blood plasma is not predominately ferric citrate. Metallomics. 2018;10 (6):802-817.
Pandey, A, Pain, J, Dziuba, N, Pandey, AK, Dancis, A, Lindahl, PA et al.. Mitochondria Export Sulfur Species Required for Cytosolic tRNA Thiolation. Cell Chem Biol. 2018;25 (6):738-748.e3.
Moore, MJ, Wofford, JD, Dancis, A, Lindahl, PA. Recovery of mrs3Δmrs4Δ Saccharomyces cerevisiae Cells under Iron-Sufficient Conditions and the Role of Fe580. Biochemistry. 2018;57 (5):672-683.
Kuppuswamy, S, Wofford, JD, Joseph, C, Xie, ZL, Ali, AK, Lynch, VM et al.. Structures, Interconversions, and Spectroscopy of Iron Carbonyl Clusters with an Interstitial Carbide: Localized Metal Center Reduction by Overall Cluster Oxidation. Inorg Chem. 2017;56 (13):7575.
Kuppuswamy, S, Wofford, JD, Joseph, C, Xie, ZL, Ali, AK, Lynch, VM et al.. Structures, Interconversions, and Spectroscopy of Iron Carbonyl Clusters with an Interstitial Carbide: Localized Metal Center Reduction by Overall Cluster Oxidation. Inorg Chem. 2017;56 (10):5998-6012.
Wofford, JD, Chakrabarti, M, Lindahl, PA. Mössbauer Spectra of Mouse Hearts Reveal Age-dependent Changes in Mitochondrial and Ferritin Iron Levels. J. Biol. Chem. 2017;292 (13):5546-5554.
Lindahl, PA, Moore, MJ. Labile Low-Molecular-Mass Metal Complexes in Mitochondria: Trials and Tribulations of a Burgeoning Field. Biochemistry. 2016;55 (30):4140-53.