"Sabeeha has blazed new pathways that have allowed us to better understand how organisms take advantage of metal ions to create useful energy for biosynthesis," said Steven Clarke, UCLA professor of chemistry and biochemistry, and director of UCLA's Molecular Biology Institute. "Most importantly, she has demonstrated the plasticity that organisms can use to substitute one metal for another when environmental conditions are altered. She has shown that this molecular flexibility is crucial for maintaining life when the outside world changes."
Merchant, who joined UCLA's faculty in 1987, was a postdoctoral scholar at Harvard in the mid-1980s, conducting molecular biology research, when she learned of a mystery that she wanted to solve. Copper is an essential nutrient, for humans as well as plants where copper is required for photosynthesis, and Merchant was surprised to read a research paper showing that algae could grow without copper.
"The algae made a back-up iron-containing protein that served the same function as the copper protein," Merchant said. "If you give them copper, they will use it, but if you take the copper away, they figure out a way around it. Many species of algae can do this switch. Somehow the algae know how much copper is present, but how do they know? They must have a way of measuring the copper; there must be an unknown mechanism; I wanted to learn what that mechanism is and how it works."
She started to conduct research at the molecular level, and over the years, she has largely succeeded in solving this mystery. Indeed, last December, she published the results of a major research effort from her laboratory, in the journal Proceedings of the National Academy of Sciences. That research concerns a specific protein molecule she has identified in cells that she believes measures the copper and responds to whether copper is present in a green alga called Chlamydomonas, which scientists use as a model for studying photosynthesis in plants. The molecule is a critical element of the mechanism that creates the back-up pathway, Merchant said.
While the protein contains 1,232 amino acids, only a tiny portion of it, approximately 70 amino acids, may be involved in binding copper, she said.
"Somehow copper is changing the properties of this region of the protein," Merchant said. "Exactly how the 70-amino acid region acts is not yet known; how is the switch turned on? We hope to learn answers to these questions."
Mechanisms that apply in algae also apply in many other forms of life, and other kinds of cells, including those of plants and mammals.
"We study algae to understand how cells work," Merchant said. "It's easier to conduct research with a micro-organism, and to see the metabolic defects when you remove metals."
Starting with her postdoctoral research, she identified and cloned two important genes and studied how they are turned on and off in response to copper. Her UCLA laboratory also is studying the role of the 70-amino acid region in the metabolism of zinc, and the group conducts research on iron as well. Merchant thinks comparable resource allocation occurs with iron and zinc as with copper, and is conducting research to identify the biochemistry, including the critical genes and proteins, and how they work.
"Cells take only the amount of copper that they need," Merchant said. "When there's a deficiency, certain enzymes get a higher priority than others."
Using an analogy, Merchant said, "If you have three children and a dog, and not enough food to feed them all, you might choose to give all the food to your kids; that's apparently what happens in our bodies -- prioritized allocation of nutrients like copper. This happens not just in algae, but in humans as well. Some copper enzymes in humans are more important than others, such as those involved in respiratory metabolism. The human body has mechanisms to preferentially allocate copper enzymes to where they are needed most."
Copper nutrition is not a big human health problem, except in cases of malnutrition and with premature infants, Merchant said.
Her research in Chlamydomonas may reveal mechanisms that work in humans and animals, as well.
"I want to know how nature works, and also hope our research has an impact on human nutrition," she said.
Merchant was chosen to receive the Gilbert Morgan Smith Medal "for her pioneering discoveries in the assembly of metalloenzymes and the regulated biogenesis of major complexes of the photosynthetic apparatus in green algae," the National Academy of Sciences said.
The medal has been presented every third year since 1979.
The National Academy of Sciences is a nonprofit society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Since 1863, the National Academy of Sciences has served to "investigate, examine, experiment, and report upon any subject of science or art" whenever called upon to do so by any department of the government.
Merchant has been awarded research grants from the National Institutes of Health within the U.S. Department of Health and Human Services, the U.S. Department of Energy, and the U.S. Department of Agriculture.
She was elected a Fellow of the American Association for the Advancement of Science last year, and is presently associate director of UCLA's Molecular Biology Institute and chair of UCLA's molecular biology interdepartmental Ph.D. program, in addition to her faculty appointment in the UCLA Department of Chemistry and Biochemistry.
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