Faculty Research Page

Sabeeha Merchant

Sabeeha Merchant

Professor of Biochemistry, Biophysics and Structural Biology*
*and of Plant and Microbial Biology

Lab Homepage: https://merchant.berkeley.edu/

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Research Interests

We seek to understand the dynamics of essential trace-metal - copper, zinc, iron, manganese - metabolism and homeostasis in the reference green alga Chlamydomonas reinhardtii using state of the art methods including classical genetics, transcriptomics and proteomics, elemental analysis and high-resolution metal imaging. The group also uses comparative genomics to extend the discoveries throughout the green algal lineage. These projects involve genome sequencing and assembly, phylogenomics and bioinformatics.

Current Projects

Metal Economy
More than 80 of the 92 naturally occurring elements are found in living organisms, but 12 of the low mass elements, which are also high abundance elements on Earth, constitute > 99% of the biomass. Yet, the others, despite their occurrence at trace levels, are essential for life because they enable the diverse chemistries of living cells. Organisms use metals like copper, iron, manganese, molybdenum, vanadium, which have multiple stable oxidation states, for reducing nitrogen gas to ammonium, for using light to convert carbon-dioxide and water to carbohydrate, and for extracting energy from inorganic or organic chemicals to sustain life. At the same time, their reactivity can make these very elements harmful in the biological environment, especially in the presence of oxygen. Too little means that enzymes that use the trace metals as catalytic cofactors will not function, and too much means that the metals may react promiscuously.

For this reason, there are homeostatic mechanisms to maintain elemental quotas in biology. One evolutionary adaptation to limitation in a particular element is the reduce, reuse, recycle paradigm. For instance, when faced with Fe deficiency, an organism can reduce its inventory of iron-containing proteins by replacing them with iron-independent catalysts. In situations of Fe starvation or sustained deficiency, an organism can remove Fe from one protein and reuse it in a different - more critical for life - protein. These mechanisms have been discovered through classical genetics and biochemistry in multiple microbes, revealing metabolic signatures for elemental economy. Comparative genomics and metagenomics indicate widespread utilization of these economies in nature.

We use Chlamydomonas reinhardtii as a reference system for dissecting the signaling pathways involved in metal sensing, sparing and homeostasis in the context of chloroplast biology and photosynthesis.
Also see Merchant, S.S., Helmann, J.D. (2012) Elemental economy: microbial strategies for optimizing growth in the face of nutrient limitation. Adv. Microbiol. Physiol. 60: 91-210 for more information.
For more details on the Cu and Fe projects are available at https://merchant.berkeley.edu/

Photosynthetis and Comparative Algal Genomics
Algae are distributed throughout the tree of life with polyphyletic origin; their defining characteristic is the presence of a photosynthetic plastid. There is remarkable diversity among the algae. They inhabit temperate and tropical soils and fresh waters, polar permafrost, as well as marine environments. Extremophile algae, like Dunaliella species, may inhabit the oversaturated salt lakes or acid lakes at pH 0! Advances in sequencing technology and computational methods are giving us a breadth of genomic data that can be used to understand the breadth of metabolism in this important group in the microbial world.

The proteomes of diverse algae can be used to infer a paleontological record of environments experienced by their ancestors. Algae in Archaeplastida contain primary plastids that originated from an endosymbiotic relationship with a cyanobacterium. These algae share a common ancestor with land plants. Outside this group, there are algae that originated from one or more endosymbiotic relationships with a eukaryotic alga, giving rise to organisms with secondary or tertiary plastids. Among the algae in Archaeplastida are Chlamydomonas, a key reference organism for fundamental discovery in photosynthesis and chloroplast metabolism, halotolerant Dunaliella spp., of commercial interest as a rich natural source of beta-carotene, and Chromochloris zofingiensis, which we are lifting up as a biofuels reference organism for its remarkable capacity for accumulating triacylglycerols (biodiesel precursors).

For each organism, we have high quality chromosome-level genome assemblies, and transcript-based structural annotations. For Chlamydomonas, we use highly synchronized cultures in flat panel bioreactors to generate multi-layered genome-wide datasets anchored to physiology to dissect daily metabolic rhythms and patterns. Similar approaches in Chr. zofingiensis will enable the application of synthetic biology in phototrophs for biofuels and high value bioproducts. For Dunaliella, our interest is in using cryo-EM approaches to get a view of the dynamics of the photosynthetic apparatus during acclimation to extreme environments.

Also see Blaby-Haas, C.E., Merchant, S.S. (2019) Comparative and functional algal genomics. Annu. Rev. Plant Biol. 70:605-638. for more information.
This work is funded by the DOE 
We collaborate with Kris Niyogi, Mary Lipton, Trent Northen, Crysten Blaby and Matteo Pellegrini on these projects.

Algal-Bacterial Interactions

We have a good picture of algal physiology and metabolism in axenic laboratory cultures; yet, in nature, algae are associated with heterotrophic bacteria. We are using reference organisms, Chlamydomonas reinhardtii for the alga, and Mesorhizobium loti for the bacterium, to develop a co-culture system which can be monitored by an array of genome-wide analytical techniques to understand the molecular physiology of such algal-bacterial interactions related to the timing and occurrence of metabolite exchange especially in the context of the diurnal cycle, and how initiation of the symbiotic interaction impacts genome-wise patterns of gene expression. We hope to distinguish symbiosis-specific genes and assess whether there are favorable windows of opportunity for establishing the interaction.

Selected Publications

145. Strenkert, D., Limso, C.A., Fatihi, A., Schmollinger, S., Basset, G.J., Merchant, S.S. (2016)
Genetically programmed changes in photosynthetic cofactor metabolism in copper deficient Chlamydomonas.
J. Biol. Chem. 291:19118 –19131.

148. Kumar, D., Strenkert, D., Patel-King, R.S., Leonard, M.T., Merchant, S.S., Mains, R.E., King, S.M., Eipper, B.A. (2017).
A bioactive peptide amidating enzyme is required for ciliogenesis.
Elife. 6. pii: e25728

149. Roth, M.S., Cokus, S.J., Gallaher, S.D., Walter, A., Lopez, D., Erickson, E., Endelman, B., Westcott, D., Larabell, C., Merchant, S.S., Pellegrini, M., Niyogi, K.K. (2017)
Chromosome-level genome assembly and transcriptome of the green alga Chromochloris zofingiensis illuminates astaxanthin production.
Proc. Natl. Acad. Sci. USA 14:E4296-E4305.

150. Xue, Y., Schmollinger, S., Attar, N., Campos, O.A., Vogelauer, M., Carey, M.F., Merchant, S.S., Kurdistani, S.K. (2017)
Endoplasmic reticulum–mitochondria junction is required for iron homeostasis.
J. Biol. Chem. 292:13197-13204.

151. Lojek, L.J., Farrand, A.J., Wisecaver, J.H., Blaby-Haas, C.E., Michel, B.W., Merchant, S.S., Rokas, A., Skaar, E.P. (2017)
Chlamydomonas reinhardtii LFO1 is an IsdG family heme oxygenase.
mSphere. 2: e00176-17.

152. Blaby-Haas, C.E., Merchant, S.S. (2017)
Regulating trace metal economy in algae.
Curr. Opin. Plant Biol. 39:88-96.

153. Wittkopp, T.M., Schmollinger, S., Saroussia, S.I., Hu, W., Fane, Q., Gallaher, S.D., Leonard, M.T., Soubeyrand, E., Basset, G.J., Merchant, S.S., Grossman, A.R., Duanmu, D., Lagarias, J.C. (2017)
Bilin-dependent photoacclimation in Chlamydomonas reinhardtii.
The Plant Cell 29:2711-2726.

154. Gallaher, S.D., Fitz-Gibbon, S.T., Strenkert, D., Purvine, S.O., Pellegrini, M., Merchant, S.S. (2018)
High-throughput sequencing of the chloroplast and mitochondrion of Chlamydomonas reinhardtii to generate improved de novo assemblies, analyze expression patterns and transcript speciation, and evaluate diversity among laboratory strains and wild isolates.
The Plant J. 93:545-565.

155. Fristedt, R., Hu, C., Wheatley, N., Roy, L., Wachter, R., Savage, L., Kramer, D., Merchant, S.S., Yeates, T.O., Croce, R. (2018).
RAF2 is a Rubisco assembly factor in Arabidopsis thaliana.
The Plant J. 94:146-156.

156. Mosalaganti, S., Kosinski, J., Albert, S., Schaffer, M., Strenkert, D., Salomé, P.A., Merchant, S.S., Plitzko, J.M., Baumeister, W., Engel, B.D., Beck, M. (2018).
In situ architecture of the algal nuclear pore complex.
Nature Comm. 9:2361.

157. Blaby-Haas, C.E., M.D. Page, Merchant, S.S. (2018)
Using YFP as a reporter of gene expression in the green alga Chlamydomonas reinhardtii.
Methods Mol. Biol. 1755, 135-148.

158. Li, M., van Zee, M., Riche, C.T., Tofig, B., Gallaher, S.D., Merchant, S.S., Damoiseaux, R., Goda, K., Di Carlo, D. (2018)
A gelatin microdroplet platform for high-throughput sorting of hyperproducing single-cell-derived microalgal clones.
Small. 14:e1803315.

159. Blaby-Haas, C.E., Merchant, S.S. (2019)
Comparative and functional algal genomics.
Annu. Rev. Plant Biol. 70:605-638.

160. Strenkert, D., Schmollinger, S., Gallaher, S.D., Salomé, P., Purvine, S.O., Nicora, C., Mettler-Altmann, T., Soubeyrand, E., Weber, A.P.M., Lipton, M., Basset, G.J., Merchant, S.S. (2019).
Multi-omics resolution of molecular events of a day in the life of Chlamydomonas.
Proc. Natl. Acad. Sci. USA 116: 2374-2385.

161. Armaleo, D., Mueller, O., Lutzoni, F., Andrésson, Ó., Blanc, G., Bode, H.B., Collart, F.R., Dal Grande, F., Dietrich, F., Grigoriev, I.V., Joneson, S., Kuo, A., Larsen, P.E., Logsdon, J.M., Lopez, D., Martin, F., May, S.P., McDonald, T.R., Merchant, S.S., Miao, V., Morin, E., Oono, R., Pellegrini, M., Rubinstein, N., Sanchez-Puerta, M.V., Savelkoul, E., Schmitt, I., Slot, J.C., Soanes, D., Szövényi, P., Talbot, N., Veneault-Fourrey, C., Xavier, B.B. (2019)
The lichen symbiosis re-viewed through the genomes of Cladonia grayi and its algal partner Asterochloris glomerata.
BMC Genomics, 20:605.

162.Roth, M.S., Gallaher, S.D., Westcott, D.J., Iwai, M., Louie, K.B., Mueller, M., Walter, A., Foflonker, F., Bowen, B.P., Ataii, N.N., Song, J., Chen, J.-H., Blaby-Haas, C., Larabell, C., Auer, M., Northen, T., Merchant, S.S., Niyogi, K.K. (2019)
Regulation of oxygenic photosynthesis during trophic transitions in the green alga Chromochloris zofingiensis.
The Plant Cell 31:579-601. doi.org/10.1105/tpc.18.00742

163. Salomé, P.A., Merchant, S.S. (2019)
A series of fortunate events: Introducing Chlamydomonas as a reference organism.
The Plant Cell, 31:1682-1707.

164. Tsednee, M., Castruita, M., Salome, P.A., Sharma, A., Lewis, B.E., Schmollinger, S.R., Holbrook, K., Otegui, M., Khatua, K., Das, S., Datta, A., Chen, S., Ramon, C., Ralle, M., Weber, P.K., Stemmler, T.L., Pett-Ridge, J., Hoffman, B.M., Merchant, S.S. (2019)
Hyper-accumulated Mn, co-localized in acidocalcisomes with Ca and P, can be mobilized in Mn-deficient situations.
J. Biol. Chem. 294, 17626-17641.

165. Amstutz, C.L., Fristedt, R., Schultink, A., Merchant, S.S., Niyogi, K.K., Malnoë, A. (2020)
An atypical short-chain dehydrogenase–reductase functions in the relaxation of photoprotective qH in Arabidopsis
Nature Plants 6, 154-166.

A full list of Publications is availabe at https://merchant.berkeley.edu/

Last Updated 2020-05-23