Within an Antarctic Sea Squirt, Scientists Discover a Bacterial Species With Promising Anti-Melanoma Properties

Within an Antarctic Sea Squirt, Scientists Discover a Bacterial Species With Promising Anti-Melanoma Properties

Within an Antarctic Sea Squirt, Scientists Discover a Bacterial Species With Promising Anti-Melanoma Properties

December 1, 2021
RENO, NEV.

By Kelsey Fitzgerald

Antarctic Sea Squirt
Melanoma
Health

Above: Late spring at Arthur Harbor. The waters surrounding Anvers Island, Antarctica, are home to a species of sea squirt called Synoicum adareanum. New research has traced the production of palmerolide A, a key compound with anti-melanoma properties, to a member of this sea squirt’s microbiome.

Credit: Alison E. Murray, DRI

New study brings important advances for Antarctic science and natural products chemistry

There are few places farther from your medicine cabinet than the tissues of an ascidian, or “sea squirt,” on the icy Antarctic sea floor – but this is precisely where scientists are looking to find a new treatment for melanoma, one of the most dangerous types of skin cancer.

In a new paper that was published today in mSphere, a research team from DRI, Los Alamos National Laboratory (LANL), and the University of South Florida (USF) made strides toward their goal, successfully tracing a naturally-produced melanoma-fighting compound called “palmerolide A” to its source: a microbe that resides within Synoicum adareanum, a species of ascidian common to the waters of Antarctica’s Anvers Island archipelago.

“We have long suspected that palmerolide A was produced by one of the many types of bacteria that live within this ascidian host species, S. adareanum,” explained lead author Alison Murray, Ph.D., research professor of biology at DRI. “Now, we have actually been able to identify the specific microbe that produces this compound, which is a huge step forward toward developing a naturally-derived treatment for melanoma.”

Synoicum adareanum

Synoicum adareanum in 80 feet of water at Bonaparte Point, Antarctica. New research has traced the production of palmerolide A, a key compound with anti-melanoma properties, to a suite of genes coded in the genome by a member of this sea squirt’s microbiome.

Credit: Bill J. Baker, University of South Florida.
Discovery of an Antarctic ascidian-associated uncultivated Verrucomicrobia with antimelanoma palmerolide biosynthetic potential

The full study, Discovery of an Antarctic ascidian-associated uncultivated Verrucomicrobia with anti-melanoma palmerolide biosynthetic potential, is available from mSphere: https://doi.org/10.1128/msphere.00759-21.

The bacterium that the team identified is a member of a new and previously unstudied genus, Candidatus Synoicihabitans palmerolidicus. This advance in knowledge builds on what Murray and her colleagues have learned across more than a decade of research on palmerolide A and its association with the microbiome (collective suite of microbes and their genomes) of the host ascidian, S. adareanum.

In 2008, Murray worked with Bill Baker, Ph.D., professor of chemistry at USF and Christian Riesenfeld, Ph.D., postdoctoral researcher at DRI to publish a study on the microbial diversity of a single S. adareanum organism. In 2020, the team expanded to include additional researchers from LANL, USF, and the Université de Nantes, and published new work identifying the “core microbiome” of S. adareanum – a common suite of 21 bacterial species that were present across 63 different samples of S. adareanum collected from around the Anvers Island archipelago.

In the team’s latest research, they looked more closely at the core microbiome members identified in their 2020 paper to determine which of the 21 types of bacteria were responsible for the production of palmerolide A. They conducted several rounds of environmental genome sequencing, followed by automated and manual assembly, gene mining, and phylogenomic analyses, which resulted in the identification of the biosynthetic gene cluster and palmerolide A-producing organism.

“This is the first time that we’ve matched an Antarctic natural product to the genetic machinery that is responsible for its biosynthesis,” Murray said. “As an anti-cancer therapeutic, we can’t just go to Antarctica and harvest these sea squirts en masse, but now that we understand the underlying genetic machinery, it opens the door for us to find a biotechnological solution to produce this compound.”

“Knowing the producer of palmerolide A enables cultivation, which will finally provide sufficient quantity of the compound for needed studies of its pharmacological properties,” added Baker.

 

A diver collects samples of Synoicum adareanum in support of a microbiome and biosynthetic gene cluster study. Palmer Station Antarctica, March 2011.

Credit: Bill Dent, University of South Florida.

Many additional questions remain, such as how S. adareanum and its palmerolide-producing symbiont are distributed across the landscape in Antarctic Oceans, or what role palmerolide A plays in the ecology of this species of ascidian.  Likewise, a detailed investigation into how the genes code for the enzymes that make palmerolide A is the subject of a new report soon to be published.

To survive in the harsh and unusual environment of the Antarctic sea floor, ascidians and other invertebrates such as sponges and corals have developed symbiotic relationships with diverse microbes that play a role in the production of features such as photoprotective pigments, bioluminescence, and chemical defense agents. The compounds produced by these microbes may have medicinal and biotechnological applications useful to humans in science, health and industry. Palmerolide A is one of many examples yet to be discovered.

“Throughout the course of disentangling the many genomic fragments of the various species in the microbiome, we discovered that this novel microbe’s genome appears to harbor multiple copies of the genes responsible for palmerolide production,” said Patrick Chain, Ph.D., senior scientist and Laboratory Fellow with LANL. “However the role of each copy, and regulation, for example, are unknown. This suggests palmerolide is likely quite important to the bacterium or the host, though we have yet to understand it’s biological or ecological role within this Antarctic setting.”

“This is a beautiful example of how nature is the best chemist out there,” Murray added. “The fact that microbes can make these bioactive and sometimes toxic compounds that can help the hosts to facilitate their survival is exemplary of the evolutionary intricacies found between hosts and their microbial partners and the chemical handshakes that are going on under our feet on all corners of the planet.”

Diver in the Antarctic Peninsula

Andrew Schilling (University of South Florida) dives in 100 feet of water at Cormorant Wall, Antarctica. Samples for microbiome characterization were collected by SCUBA divers working in the chilly subzero seas off Anvers Island, in the Antarctic Peninsula.

Credit: Bill J. Baker, University of South Florida. 

More information:

The full study, Discovery of an Antarctic ascidian-associated uncultivated Verrucomicrobia with antimelanoma palmerolide biosynthetic potential, is available from mSphere: https://doi.org/10.1128/msphere.00759-21.

Study authors included Alison Murray (DRI), Chein-Chi Lo (LANL), Hajnalka E. Daligault (LANL), Nicole E. Avalon (USF), Robert W. Read (DRI), Karen W. Davenport (LANL), Mary L. Higham (DRI), Yuliya Kunde (LANL), Armand E.K. Dichosa (LANL), Bill J. Baker (USF), and Patrick S.G. Chain (LANL).

This study was made possible with funding from the National Institutes of Health (CA205932), the National Science Foundation (OPP-0442857, ANT-0838776, and PLR-1341339), and DRI (Institute Project Assignment).

###

About DRI

The Desert Research Institute (DRI) is a recognized world leader in basic and applied environmental research. Committed to scientific excellence and integrity, DRI faculty, students who work alongside them, and staff have developed scientific knowledge and innovative technologies in research projects around the globe. Since 1959, DRI’s research has advanced scientific knowledge on topics ranging from humans’ impact on the environment to the environment’s impact on humans. DRI’s impactful science and inspiring solutions support Nevada’s diverse economy, provide science-based educational opportunities, and inform policymakers, business leaders, and community members. With campuses in Las Vegas and Reno, DRI serves as the non-profit research arm of the Nevada System of Higher Education. For more information, please visit www.dri.edu. 

About The University of South Florida

The University of South Florida is a high-impact global research university dedicated to student success. Over the past 10 years, no other public university in the country has risen faster in U.S. News and World Report’s national university rankings than USF. Serving more than 50,000 students on campuses in Tampa, St. Petersburg and Sarasota-Manatee, USF is designated as a Preeminent State Research University by the Florida Board of Governors, placing it in the most elite category among the state’s 12 public universities. USF has earned widespread national recognition for its success graduating under-represented minority and limited-income students at rates equal to or higher than white and higher income students. USF is a member of the American Athletic Conference. Learn more at www.usf.edu.

About Los Alamos National Laboratory

Los Alamos National Laboratory, a multidisciplinary research institution engaged in strategic science on behalf of national security, is managed by Triad, a public service oriented, national security science organization equally owned by its three founding members: Battelle Memorial Institute (Battelle), the Texas A&M University System (TAMUS), and the Regents of the University of California (UC) for the Department of Energy’s National Nuclear Security Administration. Los Alamos enhances national security by ensuring the safety and reliability of the U.S. nuclear stockpile, developing technologies to reduce threats from weapons of mass destruction, and solving problems related to energy, environment, infrastructure, health, and global security concerns.

 

Early Human Activities Impacted Earth’s Atmosphere More Than Previously Known

Early Human Activities Impacted Earth’s Atmosphere More Than Previously Known

Early Human Activities Impacted Earth’s Atmosphere More Than Previously Known

Oct 6, 2021
RENO, NV
By Kelsey Fitzgerald

Climate Change
Earth’s Atmosphere
Ice Cores

Above: After a storm at the drilling camp on James Ross Island, northern Antarctic Peninsula.
Credit: Robert Mulvaney
New study links an increase in black carbon in Antarctic ice cores to Māori burning practices in New Zealand more than 700 years ago
drilling the James Ross Island ice core
The James Ross Island core drilled to bedrock in 2008 by the British Antarctic Survey provided an unprecedented record of soot deposition in the northern Antarctic Peninsula during the past 2000 years and revealed the surprising impacts of Māori burning in New Zealand starting in the late 13th century. Robert Mulvaney, Ph.D., pictured here led collection of the core.
Credit: Jack Triest
nature-article-screenshot

The full text of the study, Hemispheric black carbon increase after 13th C Māori arrival in New Zealand, is available from Nature: https://www.nature.com/articles/s41586-021-03858-9

Reno, Nev. (October 6, 2021) – Several years ago, while analyzing ice core samples from Antarctica’s James Ross Island, scientists Joe McConnell, Ph.D., and Nathan Chellman, Ph.D., from DRI, and Robert Mulvaney, Ph.D., from the British Antarctic Survey noticed something unusual: a substantial increase in levels of black carbon that began around the year 1300 and continued to the modern day.

Black carbon, commonly referred to as soot, is a light-absorbing particle that comes from combustion sources such as biomass burning (e.g. forest fires) and, more recently, fossil fuel combustion. Working in collaboration with an international team of scientists from the United Kingdom, Austria, Norway, Germany, Australia, Argentina, and the U.S., McConnell, Chellman, and Mulvaney set out to uncover the origins of the unexpected increase in black carbon captured in the Antarctic ice. 

The team’s findings, which published this week in Nature, point to an unlikely source: ancient Māori land-burning practices in New Zealand, conducted at a scale that impacted the earth’s atmosphere across much of the Southern Hemisphere and dwarfed other preindustrial emissions in the region during the past 2,000 years.  

“The idea that humans at this time in history caused such a significant change in atmospheric black carbon through their land clearing activities is quite surprising,” said McConnell, research professor of hydrology at DRI who designed and led the study. “We used to think that if you went back a few hundred years you’d be looking at a pristine, pre-industrial world, but it’s clear from this study that humans have been impacting the environment over the Southern Ocean and the Antarctica Peninsula for at least the last 700 years.” 

Norwegian US East Antarctic Traverse
Four ice cores from continental Antarctica were drilled in East Antarctica, including two as part of the Norwegian-American International Polar Year Antarctic Scientific Traverse.
Credit: Stein Tronstad
Tracing the black carbon to its source 

To identify the source of the black carbon, the study team analyzed an array of six ice cores collected from James Ross Island and continental Antarctica using DRI’s unique continuous ice-core analytical system. The method used to analyze black carbon in ice was first developed in McConnell’s lab in 2007.  

While the ice core from James Ross Island showed a notable increase in black carbon beginning around the year 1300, with levels tripling over the 700 years that followed and peaking during the 16th and 17th centuries, black carbon levels at sites in continental Antarctica during the same period of time stayed relatively stable.  

Andreas Stohl, Ph.D., of the University of Vienna led atmospheric model simulations of the transport and deposition of black carbon around the Southern Hemisphere that supported the findings.  

“From our models and the deposition pattern over Antarctica seen in the ice, it is clear that Patagonia, Tasmania, and New Zealand were the most likely points of origin of the increased black carbon emissions starting about 1300,” said Stohl.  

After consulting paleofire records from each of the three regions, only one viable possibility remained: New Zealand, where charcoal records showed a major increase in fire activity beginning about the year 1300. This date also coincided with the estimated arrival, colonization, and subsequent burning of much of New Zealand’s forested areas by the Māori people.  

This was a surprising conclusion, given New Zealand’s relatively small land area and the distance (nearly 4,500 miles), that smoke would have travelled to reach the ice core site on James Ross Island. 

“Compared to natural burning in places like the Amazon, or Southern Africa, or Australia, you wouldn’t expect Māori burning in New Zealand to have a big impact, but it does over the Southern Ocean and the Antarctic Peninsula,” said Chellman, postdoctoral fellow at DRI. “Being able to use ice core records to show impacts on atmospheric chemistry that reached across the entire Southern Ocean, and being able to attribute that to the Māori arrival and settlement of New Zealand 700 years ago was really amazing.” 

 

Graphic showing increase in black carbon at the year 1300 and inset of globe showing the distance ash travelled from new zealand to antarctica
Black carbon deposition during the past 2000 years measured in ice cores from Dronning Maud Land in continental Antarctica and James Ross Island at the northern tip of the Antarctic Peninsula. Atmospheric modeling and local burning records indicate that the pronounced increase in deposition in the northern Antarctic Peninsula starting in the late 13th century was related to Māori settlement of New Zealand nearly 4000 miles away and their use of fire for land clearing and management. Inset shows locations of New Zealand and ice-core drilling sites in Antarctica.
Credit: DRI
Research impacts 

The study findings are important for a number of reasons. First, the results have important implications for our understanding of Earth’s atmosphere and climate. Modern climate models rely on accurate information about past climate to make projections for the future, especially on emissions and concentrations of light-absorbing black carbon linked to Earth’s radiative balance. Although it is often assumed that human impacts during preindustrial times were negligible compared to background or natural burning, this study provides new evidence that emissions from human-related burning have impacted Earth’s atmosphere and possibly its climate far earlier, and at scales far larger, than previously imagined.  

Second, fallout from biomass burning is rich in micronutrients such as iron. Phytoplankton growth in much of the Southern Ocean is nutrient-limited so the increased fallout from Māori burning probably resulted in centuries of enhanced phytoplankton growth in large areas of the Southern Hemisphere. 

Third, the results refine what is known about the timing of the arrival of the Māori in New Zealand, one of the last habitable places on earth to be colonized by humans. Māori arrival dates based on radiocarbon dates vary from the 13th to 14th century, but the more precise dating made possible by the ice core records pinpoints the start of large scale burning by early Māori in New Zealand to 1297, with an uncertainty of 30 years. 

“From this study and other previous work our team has done such as on 2,000-year old lead pollution in the Arctic from ancient Rome, it is clear that ice core records are very valuable for learning about past human impacts on the environment,” McConnell said. “Even the most remote parts of Earth were not necessarily pristine in preindustrial times.”  

Continuous ice core analyses at DRI

Measuring the chemistry in a longitudinal sample of an ice core on DRI’s unique ice core analytical system.

Credit: Joe McConnell

Additional information: 

The full study, Hemispheric black carbon increase after 13th C Māori arrival in New Zealand, is available from Nature: https://www.nature.com/articles/s41586-021-03858-9 

Study authors included Joseph R. McConnell (DRI), Nathan J. Chellman (DRI), Robert Mulvaney (British Antarctic Survey), Sabine Eckhardt (Norwegian Institute for Air Research), Andreas Stohl (University of Vienna), Gill Plunkett (Queen’s University Belfast), Sepp Kipfstuhl (Alfred Wegener Institut, Germany) , Johannes Freitag (Alfred Wegener Institut, Germany), Elisabeth Isaksson (Norwegian Polar Institute), Kelly E. Gleason (DRI/Portland State University), Sandra O. Brugger (DRI), David B. McWethy (Montana State University), Nerilie J. Abram (Australian National University), Pengfei Liu (Georgia Institute of Technology/Harvard University), and Alberto J. Aristarain (Instituto Antartico Argentino). 

This study was made possible with funding from the National Science Foundation (0538416, 0968391, 1702830, 1832486, and 1925417), the DRI, and the Swiss National Science Foundation (P400P2_199285).   

To learn more about DRI’s Ice Core Laboratory, please visit: https://www.dri.edu/labs/trace-chemistry-laboratory/

###

About DRI

The Desert Research Institute (DRI) is a recognized world leader in basic and applied environmental research. Committed to scientific excellence and integrity, DRI faculty, students who work alongside them, and staff have developed scientific knowledge and innovative technologies in research projects around the globe. Since 1959, DRI’s research has advanced scientific knowledge on topics ranging from humans’ impact on the environment to the environment’s impact on humans. DRI’s impactful science and inspiring solutions support Nevada’s diverse economy, provide science-based educational opportunities, and inform policymakers, business leaders, and community members. With campuses in Las Vegas and Reno, DRI serves as the non-profit research arm of the Nevada System of Higher Education. For more information, please visit www.dri.edu.