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SABEEHA MERCHANT |
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Biochemistry and Molecular Genetics of Metal Metabolism
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My research program encompasses several related projects. The longest running one deals with the mechanism of signal transduction in the context of nutritional copper homeostasis. More recently we initiated new projects on iron and manganese deficiency and metabolism. Each of these projects is intellectually and practically connected by common biological concepts and similar experimental approaches. A parallel line of investigation in the group is the mechanism of assembly of membrane-associated cytochromes c, involving compartmentalized thiol metabolism and heme biosynthesis. Another recent interest in the group is the cell biology of chlorophyll biosynthesis where our experiments center on the aerobic cyclase, a fascinating enzyme at a key step in the pathway.
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A
large fraction of proteins require metals (e.g. Zn, Cu, Fe, Mn) or metal-cofactors
(hemes, FeS centers, chlorophylls, cobalamin, molybdopterin) for function.
The metal is invariably an important structural constituent of the protein,
and it is essential for function in the proteins where it serves a catalytic
role. Metals and metal cofactors are found in every cellular compartment
and they function in diverse metabolic pathways. In one genome (of a photosynthetic
microorganism), cofactor/prosthetic group metabolism accounts for as much
as 12% of its function. The chemical reactivity, exploited in biology to
make desirable catalysts, can cause intracellular damage if it is not controlled.
Metal and metal-cofactor metabolism is, therefore, subject to tight homeostatic
regulation.
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My
group is addressing basic questions related to metal and metal cofactor
metabolism. How is the abundance / availability of a cofactor within the
cell controlled? How is the cofactor distributed to various organelles?
Is there a hierarchy of distribution when the cofactor might be limiting
(as a result of genetic lesion or sub-optimal nutritional supply)? What
are the mechanisms that ensure highly selective association between a polypeptide
and its cofactor?
Our attention
is focused on both inorganic (copper, iron, manganese) redox-active cofactors
and tetrapyrrole cofactors (heme, chlorophyll) that are found in quantity
in electron transfer pathways, such as respiration and photosynthesis. My
program is based on our discoveries relating to the biogenesis of photosynthetic
catalysts in chloroplasts and respiratory components in mitochondria.
From my Group 2006-Present
76. Merchant, S. (2006) Trace Metal Utilization in Chloroplasts in The Structure and Function of Plastids (ed. Robert R. Wise and J. Kenneth Hoober), Springer, Netherlands, pp. 199-218.
77. Merchant, S., Allen, M.D., Kropat, J., Moseley, J.L., Long, J.C., Tottey, S., Terauchi, A.M. (2006) Between a rock and a hard place: trace element nutrition in Chlamydomonas. Biochim. Biophys. Acta 1763:578-594.
78. Merchant, S., Sagasti, A. (2006) Precious metal economy. Cell Metabolism. 4:99-101.
79. Grossman, A.R., Croft, M., Gladyshev, V.N., Merchant, S., Posewitz, M.C., Prochnik, S., Spalding, M.H. (2007) Novel metabolism in Chlamydomonas through the lens of genomics. Current Opinion in Plant Biology 10(2):190-198.
80. Allen, M.D., Kropat, J. ,Tottey, S., Del Campo, J.A., Merchant, S. (2007) Manganese Deficiency in Chlamydomonas Results in Loss of Photosystem II and MnSOD Function, Sensitivity to Peroxides, and Secondary Phosphorus and Iron Deficiency. Plant Physiology 143:263-277. Online supporting information.
81. Palenik, B., Grimwood, J., Aerts, A., Rouze, P., Salamov, A., Putnam, N., Dupont C., Jorgensen, R., Derelle, E., Rombauts, S., Zhou, K., Otillar, R., Merchant, S., Podell, S., Gaasterland, T., Napoli, C., Gendler, K., Manuell, A., Tai, V., Vallon, O., Piganeau, G., Jancek, S., Heijde, M., Jabbari, K., Bowler, C., Lohr, M., Robbens, S., Werner, G., Dubchak, I., Pazour, G.J., Ren, Q., Paulsen, I., Delwiche, C., Schmutz, J., Rokhsar, D., van de Peer, Y., Moreau, H., Grigoriev, I. (2007) Tiny eukaryotes provide genomic insights into the paradox of the plankton. Proc. Natl. Acad. Sci. USA 104, 7705-7710. Online supporting information.
82. Merchant, S.S., Prochnik, S.E., Vallon, O., Harris, E.H., Karpowicz, S.J., Witman, G.B., Terry, A., Salamov, A., Fritz-Laylin, L.K., Marechal-Drouard, L., Marshall, W.F., Qu, L.-H., Nelson, D.R., Sanderfoot, A.A., Spalding, M.H., Kapitonov, V.V., Ren, Q., Ferris, P., Lindquist, E., Shapiro, H., Grimwood, J., Schmutz, J., Lucas, S., Chlamydomonas community annotation team, JGI annotation team, Grigoriev, I.V., Rokhsar, D.S., Grossman, A.R. (2007) The Chlamydomonas Genome Reveals the Evolution of Key Animal and Plant Functions. Science 318:245 - 250. Online supporting information. Press Releases: JGI, Carnegie, UCLA.
83. Allen, M.D., del Campo, J.A., Kropat, J. Merchant, S.S. (2007) FEA1, FEA2 and FRE1, Encoding Two Homologous Secreted Proteins and a Candidate Ferrireductase, are Expressed Coordinately with FOX1 and FTR1 in Iron-Deficient Chlamydomonas reinhardtii. Eukaryot. Cell 6: 1841-1852.
84. Chen, J.-C., Hsieh, S.I., Kropat, J., Merchant, S. (2008) A Ferroxidase Encoded by FOX1 Contributes to Iron Assimilation under Conditions of Poor Iron Nutrition in Chlamydomonas. Eukaryot. Cell 7: 541-545.
85. Long, J., Sommer, F., Allen, M., Lu, S., Merchant, S.S. (2008) FER1 and FER2 Encoding Two Ferritin Complexes in Chlamydomonas reinhardtii Chloroplasts Are Regulated by Iron. Genetics. 179(1): 137-147.
86. Hanikenne, M., Merchant, S.S., Hamel. P.P. (2008) Transition metal nutrition: a balance between deficiency and toxicity in The Chlamydomonas sourcebook, ed. D. Stern, in press.
87. Long, J.C., Merchant, S. (2009) Photo-oxidative stress impacts the expression of genes encoding iron metabolism components in Chlamydomonas. Photochem. Photobiol. in press.
88. Allen, M.D., Kropat, J., Merchant, S. (2009) Regulation and localization of isoforms of the aerobic oxidative cyclase in Chlamydomonas reinhardtii. Photochem. Photobiol., in press.
49. Koehler, C. M., Merchant, S., Oppliger, W., Schmid, K., Jarosch, E., Dolfini, L., Junne, T., Schatz, G., Tokatlidis, K. (1998) Tim9p, An Essential Partner Subunit of Tim10p for the Import of Mitochondrial Carrier Proteins. EMBO J. 17:6477-6486.
50. Koehler, C.M., Leuenberger, D., Merchant, S., Renold, A., Junne, T., Schatz, G. (1999) Human Deafness Dystonia Syndrome is a Mitochondrial Disease. Proc. Natl. Acad. Sci USA 96:2141-2146. see commentary
56. Springer, S., Chen, E., Duden, R., Marzioch, M., Rowley, A., Hamamoto, S., Merchant, S., Schekman, R. (2000) The p24 proteins are not essential for vesicular transport in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 97:4034-4039. see commentary.
310-206-1035
310-825-8300
GROUP MEMBERS - Merchant Group Resources
Former Ph.D. Students
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Present |
