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Contacting CBI

Dr. Lindahl


http://www.chem.tamu.edu/rgroup/lindahl/
lindahl@mail.chem.tamu.edu

Research in the Lindahl lab can be divided into three projects, all with an emphasis on the mechanism of biological phenomena. The first project involves acetyl-CoA synthase, a bifunctional Ni-Fe-S containing enzyme (see figure) which plays a critical role in the global carbon cycle and is found in certain human pathogens. Our aim is to determine the kinetics and mechanism of catalysis, and relate these to the structure and function of the novel active sites. This project involves spectroscopy, kinetics, genetics, and mathematical modeling. We are investigating the role of tunnel in the enzyme through which CO migrates. Using the stopped-flow method, we are determining the kinetics of each step in the catalytic mechanism, and will integrate these into a comprehensive kinetic model. We are also investigating whether a particular Ni in the enzyme is reduced to a zero-valent state during catalysis.

The second project involves Fe metabolism in yeast mitochondria, the site of heme and Fe/S cluster assembly. We are investigating isolated intact mitochondria by EPR/Mossbauer spectroscopy in order to determine the distribution and quanties of Fe-containing centers. We are also developing assays to detect O2 consumption and ATP production during oxidative phosphorylation, as well as to detect reactive oxygen species. Then we will examine intact mitochondria obtained from genetically modified strains in which particular Fe-related mitochondrial proteins have been deleted or overexpressed. Weare currently examining deletion and overexpression strains of YAH1p and ATM1p.

In the third project, we are computationally exploring mechanisms by which proliferating cells grow and divide. A cell modeling framework in which biochemical reaction dynamics impact the surface-to-volume ratio of the cell has been developed and incorporated into an established cell cycle mechanism. We are currently working on incorporating membrane bending energy and a primitive cytoskeleton into our model.