| THE UNIVERSITY OF QUEENSLAND |
A University of Queensland scientist is involved in an international collaboration that has proposed a new strategy for marine conservation, which involves unconventional, proactive tactics, in a paper published in Nature Climate Change.
Current actions identified in national and international policy to counter the impacts of CO2 emissions are proving inadequate, according to the authors, Greg Rau (Institute of Marine Sciences, University of California, Santa Cruz), Elizabeth McLeod (The Nature Conservancy) and Ove Hoegh-Guldberg (Global Change Institute, The University of Queensland). “It's unwise to assume we will be able to stabilize atmospheric CO2 at levels necessary to reduce or prevent ongoing damage to marine ecosystems,” said Professor Hoegh-Guldberg. “A much broader approach to marine management and mitigation options, including manipulating the environment around corals and considering the translocation of reef-building corals, must be evaluated,” he said. Marine conservation options may include: - Using shade to protect corals from the heat stress which leads to coral bleaching and death, albeit at small scales. - Actively assisting biological resilience and adaptation through spatial planning, protective culturing and possibly selective breeding - Maintain or manage ocean chemistry by adding globally abundant base minerals such as carbonates and silicates to the ocean to neutralize acidity, and improve conditions for shell formation in marine creatures - Convert CO2 from land-based waste into dissolved bicarbonates that could be added to the ocean to provide carbon sequestration and enhance alkalinity. Investigating such approaches in terms of their cost, safety and effectiveness must be part of ocean conservation and management plans in the future, according to the paper's authors. They believe more ideas need to be solicited and further research is required to determine which if any of these ideas could form the basis of safe and cost effective marine conservation strategies. “Many of these ideas may only prove practical and effective at a local or regional scale,” said Professor Hoegh-Guldberg. “However, they may still be important to local businesses that may value patches of coral reefs.” he said. “In lieu of dealing with the core problem – increasing emissions of greenhouse gases – these techniques and approaches could ultimately represent the last resort. I hope we don't end up in the position but we must at least be prepared.” Rather than waiting for damage to occur, the authors suggest that research and evaluation of non-passive measures to preserve marine communities must be undertaken before more costly and less effective restoration from CO2-related impacts is needed. According to the paper, if current trends continue, by 2050 atmospheric CO2 is expected to increase to more than 80 per cent above pre-industrial (pre-1750) levels, with the corresponding devastation to marine environments putting trillions of dollars at risk globally. From tropical to polar oceans, the magnitude and speed of the changes expected as a result of climate change and increasing ocean acidity is likely to exceed the ability of numerous marine species to adapt and survive. This rate of increase has few, if any, parallels in the past 300 million years of the Earth's history. According to the authors, some species may be able to adapt to the expected changes by migrating deeper into the ocean or further away from the equator. However, such events are rare and difficult. For example, the Great Barrier Reef would have to migrate south at the rate of 15 kilometres a year to keep pace with the predicted increases in ocean temperature while at the same time preserving its tourist and fisheries values. This seems highly unlikely given the complexity of the reef ecosystem.
Editor's Note: Original news release can be found here.
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ScienceDaily — Behaving something like ravenous monsters, tumors need plentiful supplies of cellular building blocks such as amino acids and nucleotides in order to keep growing at a rapid pace and survive under harsh conditions. How such tumors meet these burgeoning demands has not been fully understood. Now chemists at the California Institute of Technology (Caltech) have shown for the first time that a specific sugar, known as GlcNAc ("glick-nack"), plays a key role in keeping the cancerous monsters "fed." The finding suggests new potential targets for therapeutic intervention.
The new results appear in this week's issue of the journal Science.
The research team -- led by Linda Hsieh-Wilson, professor of chemistry at Caltech -- found that tumor cells alter glycosylation, the addition of carbohydrates (in this case GlcNAc) to their proteins, in response to their surroundings. This ultimately helps the cancerous cells survive. When the scientists blocked the addition of GlcNAc to a particular protein in mice, tumor-cell growth was impaired.
The researchers used chemical tools and molecular modeling techniques developed in their laboratory to determine that GlcNAc inhibits a step in glycolysis (not to be confused with glycosylation), a metabolic pathway that involves 10 enzyme-driven steps. In normal cells, glycolysis is a central process that produces high-energy compounds that the cell needs to do work. But Hsieh-Wilson's team found that when GlcNAc attaches to the enzyme phosphofructokinase 1 (PFK1), it suppresses glycolysis at an early phase and reroutes the products of previous steps into a different pathway -- one that yields the nucleotides a tumor needs to grow, as well as molecules that protect tumor cells. So GlcNAc causes tumor cells to make a trade -- they produce fewer high-energy compounds in order to get the products they need to grow and survive.
"We have identified a novel molecular mechanism that cancer cells have co-opted in order to produce intermediates that allow them to grow more rapidly and to help them combat oxidative stress," says Hsieh-Wilson, who is also an investigator with the Howard Hughes Medical Institute.
This is not the first time scientists have identified a mechanism by which tumor cells might produce the intermediates they need to survive. But most other mechanisms have involved genetic alterations, or mutations -- permanent changes that lead to less active forms of enzymes, for example. "What's unique here is that the addition of GlcNAc is dynamic and reversible," says Hsieh-Wilson. "This allows a cancer cell to more rapidly alter its metabolism depending on the environment that it encounters."
In their studies, Hsieh-Wilson's team found that this glycosylation -- the addition of GlcNAc to PFK1 -- is enhanced under conditions associated with tumors, such as low oxygen levels. They also found that glycosylation of PFK1 was sensitive to the availability of nutrients. If certain nutrients were absent, glycosylation was increased, and the tumor was able to compensate for the dearth of nutrients by changing the cell's metabolism.
When the researchers analyzed human breast and lung tumor tissues, they found GlcNAc-related glycosylation was elevated two- to fourfold in the majority of tumors relative to normal tissue from the same patients. Then, working with mice injected with human lung-cancer cells, the researchers replaced the existing PFK1 enzymes with either the normal PFK1 enzyme or a mutant form that could no longer be glycosylated. The mice with the mutant form of PFK1 showed decreased tumor growth, demonstrating that blocking glycosylation impairs cancerous growth.
The work suggests at least two possible avenues for future investigations into fighting cancer. One would be to develop compounds that prevent PFK1 from becoming glycosylated, similar to the mutant PFK1 enzymes in the present study. The other would be to activate PFK1 enzymes in order to keep glycolysis operating normally and help prevent cancer cells from altering their cellular metabolism in favor of cancerous growth.
Hsieh-Wilson's group has previously studied GlcNAc-related glycosylation in the brain. They have demonstrated, for example, that the addition of GlcNAc to a protein called CREB inhibits the protein's ability to turn on genes needed for long-term memory storage. On the other hand, they have also shown that having significantly lower levels of GlcNAc in the forebrain leads to neurodegeneration. "The current thinking is that there's a balance between too little and too much glycosylation," says Hsieh-Wilson. "Being at either extreme make things go awry, whether it's in the brain or in the case of cancer cells."
Additional Caltech coauthors on the paper, "Phosphofructokinase 1 Glycosylation Regulates Cell Growth and Metabolism," were lead author Wen Yi, a postdoctoral scholar in Hsieh-Wilson's group; Peter Clark, a former graduate student in Hsieh-Wilson's group; and William Goddard III, the Charles and Mary Ferkel Professor of Chemistry, Materials Science, and Applied Physics. Daniel Mason and Eric Peters of the Genomics Institute of the Novartis Research Foundation and Marie Keenan, Collin Hill, and Edward Driggers of Agios Pharmaceuticals were also coauthors.
The work was supported by the National Institutes of Health, the Department of Defense Breast Cancer Research Program, and a Tobacco-Related Disease Research Program postdoctoral fellowship.
