merchant summary

SABEEHA MERCHANT

Professor of Biochemistry and Member, Molecular Biology Institute; BS and PhD, University of Wisconsin-Madison; Post-doctoral Scholar, Harvard University; Searle Scholar; National Institutes of Health Research Career Development Award; UCLA Faculty Career Development Awards; Guggenheim Foundation Fellow; Charles Albert Shull Award of ASPP.

RESEARCH DESCRIPTION

My research program encompasses two major research projects: one dealing with the mechanism of signal transduction in the context of copper-responsive gene expression during adaptation to copper deficiency, and the other dealing with the mechanism of assembly of membrane-associated heme proteins in chloroplasts.

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 in the proteins where it serves a catalytic role, it is essential for function. 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 metabolism is, therefore, subject to tight homeostatic regulation.

My group is addressing basic questions related to metal and metal cofactor metabolism. How is the abundance of a cofactor controlled by the cell? How is it 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?

We have chosen, as our experimental model, two types of metal cofactors, copper and heme, the former representing inorganic cofactors, whose abundance depends on nutritional supply, transport and intracellular storage, the latter representing organic cofactors, whose abundance is determined by the operation of a biosynthetic pathway. Both are redox-active cofactors found in quantity in electron transfer pathways, such as respiration and photosynthesis, which, in eukaryotic cells, are localized to the mitochondria and chloroplasts.

For more information on our projects, chose copper or heme.

Positions for Ph.D. students and post-doctoral scholars are available on all projects. Candidates with demonstrated research productivity (publication record) and expertise in genetics or biochemistry are especially encouraged to apply for post-doctoral positions. Ph.D. candidates should apply to the Department of Chemistry and Biochemistry or to ACCESS.

PUBLICATIONS

From my Ph.D. thesis research

From my Post-Doctoral Research

From my Group 1990-1995

From my Group 1996-Present

36. Xie, Z.Y., Merchant, S. (1996) The Plastid-Encoded ccsA Gene is Required for Heme Attachment to c-type Cytochromes. J. Biol. Chem. 271:4632-4639.

37. Hill, K.L., Hassett, R., Kosman, D., Merchant, S. (1996) Copper Uptake by the Green Alga Chlamydomonas reinhardtii is Regulated in Response to Changes in Copper Ion Availability. Plant Physiol. 112:697-704.

38. Li, H.H., Quinn, J.M., Culler, D., Girard-Bascou, J., Merchant, S. (1996) Molecular Genetic Analysis of Plastocyanin Biosynthesis in Chlamydomonas reinhardtii. J. Biol. Chem. 271:31283-31289.

39. Merchant, S. (1997) Reciprocal, Copper-Responsive Accumulation of Plastocyanin and Cytochrome c6 in Algae and Cyanobacteria: a Model for Metalloregulation of Metalloprotein Synthesis in Metal Ions in Gene Regulation (ed. S. Silver and W. Walden), Chapman Hall, New York, NY., pp 450-467.

40. Kuras, R., de Vitry, C., Choquet, Y., Girard-Bascou, J., Culler, D., Buschlen, S., Merchant, S., Wollman, F.-A. (1997) Molecular Genetic Analysis of Heme Binding to Cytochrome b6. J. Biol. Chem. 272:32427-32435.

41. Inoue, K., Dreyfuss, B.W., Kindle, K.L., Stern, D.B., Merchant, S., Sodeinde, O.A. (1997) CCS1, a Nuclear Gene Required for the Maturation of Chloroplast c-type Cytochromes. J. Biol. Chem. 272:31747-31754.

42. Merchant, S., Quinn, J.M. (1998) Copper-Responsive Gene Expression in Photosynthetic Microorganisms. Methods in Enzymology 297:263-279.

43. Xie, Z.Y., Culler, D., Dreyfuss, B.W., Girard-Bascou, J., Kuras, R., Wollman, F.A., Merchant, S. (1998) Genetic Analysis of Chloroplast c-type Cytochrome Assembly: One Chloroplast Locus and At Least Four Nuclear Loci Are Required for Heme Attachment. Genetics 148:681-692.

44. Merchant, S. (1998) Synthesis of Metalloproteins Involved in Photosynthesis. In Molecular Biology of Chlamydomonas: Chloroplasts and Mitochondria. Advances in Photosynthesis (Govindjee, series ed.), Kluwer Academic Publishers, pp. 597-611.

45. Merchant, S., Dreyfuss, B.W. (1998) Metalloprotein and Cytochrome Assembly in Chloroplasts. Annu. Rev. Plant Physiol. Plant Mol. Biol. 49:25-51.

46. Xie, Z., Merchant, S. (1998) A Novel Pathway for Cytochromes c Biogenesis in Chloroplasts. Biochim. Biophys. Acta 1365:309-318.

47. Kranz, R., Lill, R., Goldman, B., Bonnard, G., Merchant, S. (1998) Molecular Mechanisms of Cytochromes c Biogenesis: Three Distinct Systems. Molecular Microbiol. 29:383-396.

48. Quinn, J.M., Nakamoto, S.S., Merchant, S. (1999) Induction of Coproporphyrinogen Oxidase in Chlamydomonas Chloroplasts Occurs via Transcriptional Regulation of Cpx1 Mediated by Copper-Response Elements and Increased Translation from a Copper-Deficiency-Specific Form of the Transcript. J. Biol. Chem. 274:14444-14454.

51. Moseley, J.L., Quinn, J.M., Eriksson, M. Merchant, S. (1999) Targets of copper-responsive gene expression in Chlamydomonas are required for PSI accumulation in copper-deficient cells of Chlamydomonas in Photosynthesis: Mechanisms and Effects (ed. G. Garab), Kluwer Academic Publishers, The Netherlands, Vol. IV, pp. 3221-3226.

52. Dreyfuss, B.W., Merchant, S. (1999) CCS5, a new locus required for chloroplast c-type cytochrome synthesis in Photosynthesis: Mechanisms and Effects (ed. G. Garab), Kluwer Academic Publishers, The Netherlands, Vol. IV, pp. 3139-3142.

53. Quinn, J.M., Merchant, S. (1999) Adaptation of Scenedesmus obliquus (Chlorophyceae) to Copper-Deficiency: Transcriptional Regulation of Pcy1 but not Cpx1. J. Phycol., in press.

54. Koehler, C.M., Merchant, S., Schatz, G. (1999) How membrane proteins travel across the mitochondrial intermembrane space. Trends in Biochem. Sci. 24:429-431.

From my sabbatical in the Schatz group at the Biozentrum in Basel

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

Books

1. Rochaix, J.-D., Goldschmidt-Clermont, M., Merchant, S., eds. (1998) Molecular Biology of Chlamydomonas: Chloroplasts and Mitochondria. Advances in Photosynthesis (Govindjee, series ed.), Kluwer Academic Publishers.

CONTACT ME

Department of Chemistry and Biochemistry

UCLA

Box 951569 (post)

607 Charles E. Young Drive East (courier)

Los Angeles, CA 90095-1569

310-206-1035

310-825-8300

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