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.

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.

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.

Positions for Ph.D. students and postdoctoral scholars may be available for all Merchant Lab projects.

Postdoctoral candidates with demonstrated research productivity (publication record) and expertise in biochemistry, cell biology, geochemistry, genetics, genomics, and microbiology are especially encouraged to apply. Please send the following to Sabeeha Merchant: a cover letter that describes your past research experience and motivation for applying to the Merchant Lab, a brief description of proposed research for your postdoctoral project, your most relevant published papers (for multi-author papers, please describe your contribution) as well as names and contact information for 3 or more potential references (letters are not needed during the initial stage).

Ph.D. candidates should apply to one of the following programs at UC Berkeley: Plant and Microbial Biology, Molecular and Cell Biology, Chemical Biology. All programs allow graduate students to rotate through multiple labs in the first year, providing a diversity of research experiences prior to selecting a lab.