From UC San Diego: “Revealing the Secrets of Seaweeds”

From UC San Diego

Mar 11,2021
Brittany Hook
Photos by Erik Jepsen/UC San Diego Communications.

UC San Diego researchers explore seaweed genome diversity in first-of-its-kind project.

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UC San Diego Ph.D. student Taylor Steele and advisor Bradley Moore (shown in the background) collect seaweed at the tide pools in La Jolla. They are working on a project to sequence the genomes of 10 different types of biosynthetically “gifted” red seaweeds found in San Diego.

San Diego’s tide pools are a popular site for visitors hoping to see some form of marine life. Revealed with the ebb and flow of the tides, these rocky coastal wonderlands are often teeming with creatures ranging from hermit crabs and octopus to small fishes and sea anemones.

But beyond the scene-stealing marine critters—if you look a little closer—you will find seaweed, or algae, and lots of it.

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Scripps Oceanography postdoctoral scholar Immo Burkhardt sifts through seagrass in search of red seaweed.

Researchers at UC San Diego are now taking a closer look at some of these locally found seaweeds in a first-of-its-kind project that explores seaweed genome diversity. Funded by the Joint Genome Institute (JGI), this research is led by marine chemist Bradley Moore and members of his lab at Scripps Institution of Oceanography.

Since the project began in 2019, researchers in the Moore Lab have been working to unravel the complex chemistry of seaweeds, particularly how they construct certain molecules that could have important applications in fields such as manufacturing and medicine. The team is currently working with the JGI to sequence the genomes of 10 different types of biosynthetically “gifted” red seaweeds found in San Diego, something that has never been done before.

“I’m excited to read some of the first genome sequences from red algae to learn how these seaweeds have evolved to chemically defend themselves from nearshore grazers,” said Moore, a professor of marine biotechnology and biomedicine at Scripps Oceanography and the Skaggs School of Pharmacy at UC San Diego. “Many chemicals naturally produced by our local seaweeds are unique to red algae and are not found in other organisms on our planet. So that fascinates me as a chemist and geneticist with the additional goal to apply the metabolic secrets of seaweeds to help solve societal challenges.”

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Some red seaweeds construct molecules that could have important applications in fields such as manufacturing and medicine.

Seaweeds represent a multi-billion-dollar industry across the world and are a source of many materials spanning the chemical and food sectors. By understanding how seaweeds work on a molecular level, this work could help natural products researchers harness seaweeds’ biosynthetic machinery in the biomanufacturing of fuels, lubricants, polymers, and other commodity and specialty chemicals.

“As our economy moves to more of a bio-based future less reliant on fossil fuels, we scientists are looking to nature to learn how they make many of the same materials that we need in society, yet not from petrochemicals but via photosynthesis,” said Moore. “So, I see lots of upsides here in making bio-based materials, pharmaceuticals, agriculture products, and more to support our growing economy.”

This project builds upon groundbreaking work done in the 1970s by Scripps Oceanography scientists William Fenical and the late D. John Faulkner. The marine chemists collected and characterized red seaweeds for the first time, identifying interesting chemicals in the seaweed samples by grinding them up and extracting the chemicals out of them. The Moore Lab is now revisiting this initial work with fresh eyes and taking it a step further using genome sequencing, a process which tells scientists the kind of genetic information that is carried in a particular DNA segment.

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Ph.D. student Taylor Steele carries a vat of liquid nitrogen, used to preserve samples, to the tide pools.

Red seaweeds are of interest to marine chemists because certain types are known for their incredible ability to utilize halogens, a group of non-metallic elements that includes bromine and chlorine. The main focus of this genome sequencing project is to discover how some “chemically interesting” seaweeds are able to incorporate halogens onto the molecules that they produce—molecules that hold promise for other applications.

“The seaweeds we study are talented producers of an interesting suite of bioactive molecules,” said Taylor Steele, a member of the Moore Lab and third-year Ph.D. student in the Department of Chemistry and Biochemistry at UC San Diego. “We’re interested in the biochemistry of these seaweeds, and how we are able to re-purpose this biosynthetic machinery for other biotechnological applications. It’s almost like molecular Legos.”

Growing up in San Diego, Steele said she was an “outdoorsy kid” interested in learning about the natural world. This curiosity inspired her to pursue studies in science, “to understand the amazing underlying biochemistry going on all around you—it just can’t be seen with your naked eye,” she said.

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Moore Lab members Tristan de Rond and Immo Burkhardt search for red seaweeds at the tide pools.

Steele joined the Moore Lab in 2019 after learning about some of the innovative sequencing techniques being utilized there, plus she was encouraged by Moore’s mentorship and how he fosters a healthy lab environment. She decided to focus her Ph.D. research on the seaweed genome project, working in collaboration with Scripps postdoctoral scholar Immo Burkhardt. The research seemed to perfectly combine her interests in biochemistry and genome sequencing.

“I was excited to have a project with both computational and wet lab components. The Moore lab is focused on connecting genes to molecules, and the seaweed genome project is a great example of this philosophy,” said Steele. “I have an opportunity to do the genome sequencing, assembly, and annotation, and then take my results to the bench and also do the biochemistry.”

During a recent field outing, Steele, Moore, and several other lab members collected seaweed samples from the tide pools in La Jolla. They timed their socially distanced outing to coincide with the low tide, which provided a short window of time for the team to search the nooks and crannies of the exposed tide pools for three particular seaweed species.

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Samples intended for long-read sequencing were frozen in a vat of liquid nitrogen before being sent to the lab for PacBio sequencing.

Once the researchers found a viable sample, they would clean it by picking off any “large friends” like worms or molluscs, and then prepare the sample to be sent to the JGI for genome sequencing.

Steele said the researchers will first use short-read sequencing known as Illumina sequencing, to get a feel for what a sample looks like, and then once it has been cleared as viable, they will follow up with the more precise long-read sequencing known as PacBio sequencing. She compares the different sequencing methods to reading a book.

“With Illumina sequencing, it is like you are sequencing each word individually, and with PacBio sequencing, it is like you are reading through entire paragraphs at a time without stopping, which enables you to have a much more complete and contiguous genome,” said Steele. “That is a really valuable tool for the community and for us—the people who are hunting for genes.”

It usually takes three to six months to receive the sequencing results from the JGI, and then the results are further analyzed in the lab at Scripps. In addition to the possible biomanufacturing applications, researchers say that the resulting genomes will provide new insight into how seaweeds adapt to diverse and inhospitable environments.

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Perks of the job: Scripps Oceanography scientist Bradley Moore searches for seaweed underwater.

Tristan de Rond, a Scripps postdoctoral scholar and member of the Moore Lab, said he is impressed by the complexity of red seaweeds and their ability to thrive in unlikely places. “They are these fascinating little chemical factories found between the cracks of the rocks,” he said.

Having studied seaweeds for the past three years, Steele said she also has more of an appreciation for the “amazing amount of biodiversity” found in the tide pools.

“There are so many of these red seaweeds in our backyard that you just don’t notice until you begin to learn about them. Then you realize, holy cow, there are so many different kinds of these seaweeds out here and they make these crazy molecules,” she said.

Across campus, other researchers are also working on innovative projects involving seaweeds. Scripps marine ecologist Jennifer Smith has been working with agricultural researchers at UC Davis on a project to cultivate Asparagopsis taxiformis, a red seaweed that has been shown to reduce the amount of methane emissions from dairy cows when added to livestock feed. Smith also co-leads the California Seaweed Company, a start-up with former student Brant Chlebowski that seeks to sustainably cultivate top quality culinary seaweeds. And several other UC San Diego researchers have been collaborating on a project that utilizes algae-based materials to create biodegradable flip-flops.


Revealing the Secrets of Seaweeds

So far, Steele has made progress on sequencing three types of red seaweeds, with two more in the pipeline, and five others to be done in the near future with help from others in the lab. The project will be completed in 2022, but Steele said it will hopefully leave a “pile of genomes” that will enable future research.

“We are in a genomics era, and it has been fun to apply this technology to red seaweeds, a very understudied group of organisms,” said Steele. “My hope is that we can contribute these genomes to the community as a resource for future work.”

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Taylor Steele, Bradley Moore and other members of the Moore Lab walk along the beach during a field trip to collect seaweed in January 2021.

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Stem Education Coalition

The University of California, San Diego, is a public research university located in the La Jolla area of San Diego, California, in the United States. The university occupies 2,141 acres (866 ha) near the coast of the Pacific Ocean with the main campus resting on approximately 1,152 acres (466 ha). Established in 1960 near the pre-existing Scripps Institution of Oceanography, UC San Diego is the seventh oldest of the 10 University of California campuses and offers over 200 undergraduate and graduate degree programs, enrolling about 22,700 undergraduate and 6,300 graduate students. UC San Diego is one of America’s Public Ivy universities, which recognizes top public research universities in the United States. UC San Diego was ranked 8th among public universities and 37th among all universities in the United States, and rated the 18th Top World University by U.S. News & World Report’s 2015 rankings.

UC San Diego is organized into seven undergraduate residential colleges (Revelle; John Muir; Thurgood Marshall; Earl Warren; Eleanor Roosevelt; Sixth; and Seventh), four academic divisions (Arts and Humanities; Biological Sciences; Physical Sciences; and Social Sciences), and seven graduate and professional schools (Jacobs School of Engineering; Rady School of Management; Scripps Institution of Oceanography; School of Global Policy and Strategy; School of Medicine; Skaggs School of Pharmacy and Pharmaceutical Sciences; and the newly established Wertheim School of Public Health and Human Longevity Science). UC San Diego Health, the region’s only academic health system, provides patient care; conducts medical research; and educates future health care professionals at the UC San Diego Medical Center, Hillcrest; Jacobs Medical Center; Moores Cancer Center; Sulpizio Cardiovascular Center; Shiley Eye Institute; Institute for Genomic Medicine; Koman Family Outpatient Pavilion and various express care and urgent care clinics throughout San Diego.

The university operates 19 organized research units (ORUs), including the Center for Energy Research; Qualcomm Institute (a branch of the California Institute for Telecommunications and Information Technology); San Diego Supercomputer Center; and the Kavli Institute for Brain and Mind, as well as eight School of Medicine research units, six research centers at Scripps Institution of Oceanography and two multi-campus initiatives, including the Institute on Global Conflict and Cooperation. UC San Diego is also closely affiliated with several regional research centers, such as the Salk Institute; the Sanford Burnham Prebys Medical Discovery Institute; the Sanford Consortium for Regenerative Medicine; and the Scripps Research Institute. It is classified among “R1: Doctoral Universities – Very high research activity”. According to the National Science Foundation(US), UC San Diego spent $1.265 billion on research and development in fiscal year 2018, ranking it 7th in the nation.

UC San Diego is considered one of the country’s Public Ivies. As of February 2021, UC San Diego faculty, researchers and alumni have won 27 Nobel Prizes and three Fields Medals, eight National Medals of Science, eight MacArthur Fellowships, and three Pulitzer Prizes. Additionally, of the current faculty, 29 have been elected to the National Academy of Engineering, 70 to the National Academy of Sciences(US), 45 to the National Academy of Medicine(US) and 110 to the American Academy of Arts and Sciences.

History

When the Regents of the University of California originally authorized the San Diego campus in 1956, it was planned to be a graduate and research institution, providing instruction in the sciences, mathematics, and engineering. Local citizens supported the idea, voting the same year to transfer to the university 59 acres (24 ha) of mesa land on the coast near the preexisting Scripps Institution of Oceanography(US). The Regents requested an additional gift of 550 acres (220 ha) of undeveloped mesa land northeast of Scripps, as well as 500 acres (200 ha) on the former site of Camp Matthews from the federal government, but Roger Revelle, then director of Scripps Institution and main advocate for establishing the new campus, jeopardized the site selection by exposing the La Jolla community’s exclusive real estate business practices, which were antagonistic to minority racial and religious groups. This outraged local conservatives, as well as Regent Edwin W. Pauley.

UC President Clark Kerr satisfied San Diego city donors by changing the proposed name from University of California, La Jolla, to University of California, San Diego. The city voted in agreement to its part in 1958, and the UC approved construction of the new campus in 1960. Because of the clash with Pauley, Revelle was not made chancellor. Herbert York, first director of Lawrence Livermore National Laboratory, was designated instead. York planned the main campus according to the “Oxbridge” model, relying on many of Revelle’s ideas.

According to Kerr, “San Diego always asked for the best,” though this created much friction throughout the UC system, including with Kerr himself, because UC San Diego often seemed to be “asking for too much and too fast.” Kerr attributed UC San Diego’s “special personality” to Scripps, which for over five decades had been the most isolated UC unit in every sense: geographically, financially, and institutionally. It was a great shock to the Scripps community to learn that Scripps was now expected to become the nucleus of a new UC campus and would now be the object of far more attention from both the university administration in Berkeley and the state government in Sacramento.

UC San Diego was the first general campus of the University of California to be designed “from the top down” in terms of research emphasis. Local leaders disagreed on whether the new school should be a technical research institute or a more broadly based school that included undergraduates as well. John Jay Hopkins of General Dynamics Corporation pledged one million dollars for the former while the City Council offered free land for the latter. The original authorization for the San Diego campus given by the UC Regents in 1956 approved a “graduate program in science and technology” that included undergraduate programs, a compromise that won both the support of General Dynamics and the city voters’ approval.

Nobel laureate Harold Urey, a physicist from the University of Chicago(US), and Hans Suess, who had published the first paper on the greenhouse effect with Revelle in the previous year, were early recruits to the faculty in 1958. Maria Goeppert-Mayer, later the second female Nobel laureate in physics, was appointed professor of physics in 1960. The graduate division of the school opened in 1960 with 20 faculty in residence, with instruction offered in the fields of physics, biology, chemistry, and earth science. Before the main campus completed construction, classes were held in the Scripps Institution of Oceanography.

By 1963, new facilities on the mesa had been finished for the School of Science and Engineering, and new buildings were under construction for Social Sciences and Humanities. Ten additional faculty in those disciplines were hired, and the whole site was designated the First College, later renamed after Roger Revelle, of the new campus. York resigned as chancellor that year and was replaced by John Semple Galbraith. The undergraduate program accepted its first class of 181 freshman at Revelle College in 1964. Second College was founded in 1964, on the land deeded by the federal government, and named after environmentalist John Muir two years later. The School of Medicine also accepted its first students in 1966.

Political theorist Herbert Marcuse joined the faculty in 1965. A champion of the New Left, he reportedly was the first protester to occupy the administration building in a demonstration organized by his student, political activist Angela Davis. The American Legion offered to buy out the remainder of Marcuse’s contract for $20,000; the Regents censured Chancellor William J. McGill for defending Marcuse on the basis of academic freedom, but further action was averted after local leaders expressed support for Marcuse. Further student unrest was felt at the university, as the United States increased its involvement in the Vietnam War during the mid-1960s, when a student raised a Viet Minh flag over the campus. Protests escalated as the war continued and were only exacerbated after the National Guard fired on student protesters at Kent State University in 1970. Over 200 students occupied Urey Hall, with one student setting himself on fire in protest of the war.

Early research activity and faculty quality, notably in the sciences, was integral to shaping the focus and culture of the university. Even before UC San Diego had its own campus, faculty recruits had already made significant research breakthroughs, such as the Keeling Curve, a graph that plots rapidly increasing carbon dioxide levels in the atmosphere and was the first significant evidence for global climate change; the Kohn–Sham equations, used to investigate particular atoms and molecules in quantum chemistry; and the Miller–Urey experiment, which gave birth to the field of prebiotic chemistry.

Engineering, particularly computer science, became an important part of the university’s academics as it matured. University researchers helped develop UCSD Pascal, an early machine-independent programming language that later heavily influenced Java; the National Science Foundation Network, a precursor to the Internet; and the Network News Transfer Protocol during the late 1970s to 1980s. In economics, the methods for analyzing economic time series with time-varying volatility (ARCH), and with common trends (cointegration) were developed. UC San Diego maintained its research intense character after its founding, racking up 25 Nobel Laureates affiliated within 50 years of history; a rate of five per decade.

Under Richard C. Atkinson’s leadership as chancellor from 1980 to 1995, the university strengthened its ties with the city of San Diego by encouraging technology transfer with developing companies, transforming San Diego into a world leader in technology-based industries. He oversaw a rapid expansion of the School of Engineering, later renamed after Qualcomm founder Irwin M. Jacobs, with the construction of the San Diego Supercomputer Center(US) and establishment of the computer science, electrical engineering, and bioengineering departments. Private donations increased from $15 million to nearly $50 million annually, faculty expanded by nearly 50%, and enrollment doubled to about 18,000 students during his administration. By the end of his chancellorship, the quality of UC San Diego graduate programs was ranked 10th in the nation by the National Research Council.

The university continued to undergo further expansion during the first decade of the new millennium with the establishment and construction of two new professional schools — the Skaggs School of Pharmacy and Rady School of Management—and the California Institute for Telecommunications and Information Technology, a research institute run jointly with University of California Irvine(US). UC San Diego also reached two financial milestones during this time, becoming the first university in the western region to raise over $1 billion in its eight-year fundraising campaign in 2007 and also obtaining an additional $1 billion through research contracts and grants in a single fiscal year for the first time in 2010. Despite this, due to the California budget crisis, the university loaned $40 million against its own assets in 2009 to offset a significant reduction in state educational appropriations. The salary of Pradeep Khosla, who became chancellor in 2012, has been the subject of controversy amidst continued budget cuts and tuition increases.

On November 27, 2017, the university announced it would leave its longtime athletic home of the California Collegiate Athletic Association, an NCAA Division II league, to begin a transition to Division I in 2020. At that time, it will join the Big West Conference, already home to four other UC campuses (Davis, Irvine, Riverside, Santa Barbara). The transition period will run through the 2023–24 school year. The university prepares to transition to NCAA Division I competition on July 1, 2020.

Research

Applied Physics and Mathematics

The Nature Index lists UC San Diego as 6th in the United States for research output by article count in 2019. In 2017, UC San Diego spent $1.13 billion on research, the 7th highest expenditure among academic institutions in the U.S. The university operates several organized research units, including the Center for Astrophysics and Space Sciences (CASS), the Center for Drug Discovery Innovation, and the Institute for Neural Computation. UC San Diego also maintains close ties to the nearby Scripps Research Institute(US) and Salk Institute for Biological Studies(US). In 1977, UC San Diego developed and released the UCSD Pascal programming language. The university was designated as one of the original national Alzheimer’s disease research centers in 1984 by the National Institute on Aging. In 2018, UC San Diego received $10.5 million from the DOE National Nuclear Security Administration(US) to establish the Center for Matters under Extreme Pressure (CMEC).

The university founded the San Diego Supercomputer Center (SDSC) in 1985, which provides high performance computing for research in various scientific disciplines. In 2000, UC San Diego partnered with UC Irvine to create the Qualcomm Institute – UC San Diego(US), which integrates research in photonics, nanotechnology, and wireless telecommunication to develop solutions to problems in energy, health, and the environment.

UC San Diego also operates the Scripps Institution of Oceanography (SIO)(US), one of the largest centers of research in earth science in the world, which predates the university itself. Together, SDSC and SIO, along with funding partner universities California Institute of Technology(US), San Diego State University(US), and UC Santa Barbara, manage the High Performance Wireless Research and Education Network.