Closing in on a vaccine that’s effective against the most severe forms of malaria

Image: Ibrahim Boran

Scientists have taken another big step forward towards developing a vaccine that’s effective against the most severe forms of malaria.

Professor Denise Doolan from James Cook University’s Australian Institute of Tropical Health and Medicine (AITHM) was part of an international team that narrowed down the malaria proteins and disease-fighting antibodies that could be used to develop a vaccine against severe malaria.

She said according to the latest figures from the World Health Organisation,  there were 219 million cases of malaria worldwide in 2017, leading to an estimated 435,000 deaths.

“What makes this work so difficult is the particular survival strategy of the malaria parasite in the human body. It grows within blood cells and inserts proteins into the surface of the blood cell so it sticks to the walls of blood vessels,” Professor Doolan said.

“But it changes these proteins to escape from immune responses, and every strain has a different set of proteins, making the identification of vaccine targets extraordinarily hard.”

The team of collaborators – involving JCU, the Walter and Eliza Hall Institute of Medical Research (WEHI) at Deakin University, and malaria experts from Papua New Guinea, France and the USA – collected hundreds of PfEMP1 proteins from malaria strains from children in PNG who had been naturally infected by the disease, made a custom protein microarray of those strains, and then examined serum samples to identify which of the many PfEMP1 variants were associated with protection.

The research team managed to pinpoint which antibodies were most effective in fighting the most severe forms of malaria.

Associate Professor Alyssa Barry, who leads the Systems Epidemiology of Infection unit within the Deakin School of Medicine, said the findings from the project were a major step towards developing a viable vaccine for the disease.

“It’s the first time anyone has shown this – for years, researchers have thought that developing a malaria vaccine based on PfEMP1 would be virtually impossible, because the proteins are just so diverse,” Associate Professor Barry said.

“It’s similar to the flu vaccine, where you have to keep adjusting and updating it as the virus strains evolve from year to year. Malaria is even more diverse than influenza – one village in a country such as PNG could contain thousands of possible malaria strains. But in malaria-endemic areas, children who are repeatedly infected develop immunity to severe malaria by the time they’re about two years old, so we know antimalarial immunity is possible, and it can develop after exposure to only a few strains.”

Associate Professor Barry said while immunity to milder forms of malaria presented a “formidable obstacle”, immunity to severe malaria targets only a small subset of proteins that have many similarities between strains – making the essential components for a vaccine much easier to identify.

“Using genomic sequencing, we collected PfEMP1 proteins from different strains of malaria, measured antibodies to those proteins and then used machine learning to identify the protective antibody – the biomarker of immunity – that protects kids against disease,” she said.

“We were able to identify these antibodies by monitoring for patterns of disease, following the children in PNG for 16 months to determine which of them were susceptible to the more severe forms of the disease, and those who were protected and only experienced milder forms of the disease.

“It’s been a long road, and has involved a large team, but it’s a major step forward, and this provides hope that creating a vaccine might be possible.”

The full research findings, “Protective immunity against severe malaria in children is associated with a limited repertoire of antibodies to conserved PfEMP1 variants”, were published today in the scientific journal Cell Host & Microbe.

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Big data takes on big neurological problems

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A James Cook University scientist is part of an international team that’s used new ‘big data’ analysis to achieve a major advance in understanding neurological disorders such as Epilepsy, Alzheimer’s and Parkinson’s disease.

Dr Ashley Waardenberg, a Theme Leader from JCU’s Centre for Tropical Bioinformatics and Molecular Biology, said scientists from JCU, The Children’s Medical Research Institute, Sydney, University of Southern Denmark and Bonn University (Germany) looked at how neurons in the brain communicated with each other.

“We studied the synapse – the communication hotspot between neurons – which is a place where neurological disorders and diseases can interfere with the brain’s normal functions,” said Dr Waardenberg.

“We aimed to use new methods for mapping the protein pathways that neurons use to communicate with each other (neurotransmission) and tried to see if we could identify patterns of activity related to memory.”

“A key part of the project that I led was to develop new computational methods to assess the very large amount of data that we collected. This led to the discovery of the major proteins responsible for the changes observed in the neurons,” said Dr Waardenberg.

He said the discoveries open up many new avenues for studying the protein pathways underlying neurotransmission and how they might be linked to neurological diseases and disorders.

Dr Waardenberg said the breakthrough demonstrates how new computational methods are needed to develop insights from ‘big data’.

He said the team of scientists is releasing the paper detailing the computational methods and the thousands of new proteins sites identified as a resource to the scientific community.

“We hope that this resource will help our future understanding of neuron signaling and memory. The discovery has very important implications for understanding the mechanisms of neurotransmission and neurological disorders,” he said.

Dr Waardenberg is now aiming to establish these new methods at JCU and continue to develop new computational methods for tackling tropical diseases such as malaria.

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World First: Undersea robot dispersed microscopic baby corals to repopulate parts of the Great Barrier Reef

Larvalbot moves across the coral reef

In a world first, an undersea robot has dispersed microscopic baby corals (coral larvae) to help scientists working to repopulate parts of the Great Barrier Reef during this year’s mass coral spawning event.

Ecology and technology have combined to give nature a helping hand, using a robot to deliver heat tolerant coral larvae directly onto the Great Barrier Reef in the first small scale pilot of a new technique to help restore and recover coral reefs.

In a world first, an undersea robot has dispersed microscopic baby corals (coral larvae) to help scientists working to repopulate parts of the Great Barrier Reef during this year’s mass coral spawning event.

Six weeks after winning the Great Barrier Reef Foundation’s $300,000 Out of the Blue Box Reef Innovation Challenge, Southern Cross University’s Professor Peter Harrison and QUT’s Professor Matthew Dunbabin trialled the ground-breaking initiative on Vlasoff Reef, near Cairns in north Queensland.

Professor Dunbabin engineered QUT’s reef protector RangerBot into LarvalBot specifically for the coral restoration project led by Professor Harrison.

The project builds on Professor Harrison’s successful larval reseeding technique piloted on the southern Great Barrier Reef in 2016 and 2017 in collaboration with the Great Barrier Reef Foundation, the Great Barrier Reef Marine Park Authority (GBRMPA) and Queensland Parks & Wildlife Service (QPWS), following successful small scale trials in the Philippines funded by the Australian Centre for International Agricultural Research.

“This year represents a big step up for our larval restoration research and the first time we’ve been able to capture coral spawn on a bigger scale using large floating spawn catchers then rearing them into tiny coral larvae in our specially constructed larval pools and settling them on damaged reef areas,” Professor Harrison said.

“Winning the GBRF’s Reef Innovation Challenge meant that we could increase the scale of the work planned for this year using mega-sized spawn catchers and fast track an initial trial of LarvalBot as a novel method of dispersing the coral larvae out on to the Reef.

“With further research and refinement, this technique has enormous potential to operate across large areas of reef and multiple sites in a way that hasn’t previously been possible.

“We’ll be closely monitoring the progress of settled baby corals over coming months and working to refine both the technology and the technique to scale up further in 2019.”

This research and the larval production process was also directly supported by the recent successful SBIR 2018 Coral larval restoration research project on Vlasoff Reef led by Professor Harrison with Katie Chartrand (James Cook University) and Associate Professor David Suggett (University of Technology Sydney), in collaboration with Aroona Boat Charters, the GBRMPA and QPWS.

With a current capacity to carry around 100,000 coral larvae per mission and plans to scale up to millions of larvae, the robot gently releases the larvae onto damaged reef areas allowing it to settle and over time develop into coral polyps or baby corals.

Professor Dunbabin said LarvalBot could be compared to ‘an underwater crop duster’ operating very safely to ensure existing coral wasn’t disturbed.

“During this year’s trial, the robot was tethered so it could be monitored precisely but future missions will see it operate alone and on a much larger scale,” Professor Dunbabin said.

“Using an iPad to program the mission, a signal is sent to deliver the larvae and it is gently pushed out by LarvalBot. It’s like spreading fertiliser on your lawn.

“The robot is very smart, and as it glides along we target where the larvae need to be distributed so new colonies can form and new coral communities can develop.

“We have plans to do this again in Australia and elsewhere and I’m looking forward to working with Professor Harrison and Southern Cross University, the Great Barrier Reef Foundation and other collaborators to help tackle an important problem.”

This project builds on the work by Professor Dunbabin who developed RangerBot to help control the coral-killing crown-of-thorns starfish which is responsible for 40 per cent of the reef’s decline in coral cover.

Great Barrier Reef Foundation Managing Director Anna Marsden said: “It’s exciting to see this project progress from concept to implementation in a matter of weeks, not years. The recent IPCC report highlights that we have a very short window in which to act for the long term future of the Reef, underscoring the importance of seeking every opportunity to give our reefs a fighting chance.

“This project is testament to the power of collaboration between science, business and philanthropy. With the support of the Tiffany & Co. Foundation, whose longstanding support for coral reef conservation globally spans almost two decades, our international call for innovations to help the Reef has uncovered a solution that holds enormous promise for restoring coral reefs at scales never before possible.”

Following the success of this initial trial in 2018, the researchers plan to fully implement their challenge-winning proposal in 2019, building even larger mega spawn-catchers and solar powered floating larval incubation pools designed to rear hundreds of millions of genetically diverse, heat-tolerant coral larvae to be settled on damaged reefs through a combination of larval clouds and LarvalBots.

Learn more: Robot makes world-first baby coral delivery to Great Barrier Reef

 

 

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A glimmer of hope for the world’s coral reefs

Researchers found that the response of corals to heat stress during the second of two unprecedented back-to-back bleaching events on the Great Barrier Reef was markedly different from the first. Credit: Tane Sinclair-Taylor

The future of the world’s coral reefs is uncertain, as the impact of global heating continues to escalate. However, according to a study published today in Nature Climate Change, the response of the Great Barrier Reef to extreme temperatures in 2017 was markedly different to one year earlier, following two back-to-back bouts of coral bleaching. Remarkably, corals that bleached and survived 2016 were more resistant in 2017 to a recurrence of hot conditions.

“Dead corals don’t bleach for a second time. The north lost millions of heat-sensitive corals in 2016, and most of the survivors were the tougher species. As a result of bleaching, the mix of species is changing very rapidly,” said lead author Prof Terry Hughes, Director of the Australian Research Council Centre of Excellence for Coral Reef Studies (Coral CoE), headquartered at James Cook University.

“We were astonished to find less bleaching in 2017, because the temperatures were even more extreme than the year before,” he said.

The new research highlights the extent of damage, or “geographic footprint” of multiple coral bleaching events across the 2,300 km length of the world-heritage listed area.

The back-to-back heatwaves bring the total number of mass bleaching events on the Great Barrier Reef to four over the past two decades (in 1998, 2002, 2016 and 2017). The scientists found that only 7% of the Great Barrier Reef escaped bleaching entirely since 1998, and after the 2017 event, 61% of reefs have now been severely bleached at least once.

“We found, using the National Oceanic and Atmospheric Administration’s (NOAA) satellite-based coral bleaching tools, that corals in the north of the Great Barrier Reef were exposed to the most heat stress in 2016. A year later, the central region saw the most prolonged heating,” said co-author Dr Mark Eakin, from NOAA’s Coral Reef Watch program, in Maryland, USA.

The southern third of the Great Barrier Reef was cooler in both years due to local weather conditions, and escaped with only minor bleaching.

“It’s only a matter of time before we see another mass-bleaching event, triggered by the next marine heatwave, driven by global heating,” said co-author Dr Andrew Hoeyof Coral CoE at James Cook University. “One of the worst possible scenarios is we’ll see these southern corals succumb to bleaching in the near future.”

“The outcome in 2017 depended on the conditions experienced by the corals one year earlier. We called that ‘ecological memory,’ and show that these repeating events are now acting together in ways that we didn’t expect,” said Prof Hughes.

“We’ve never seen back-to-back mass coral bleaching before on the Great Barrier Reef, in two consecutive summers. The combined footprint has killed close to half of the corals on two-thirds of the world’s largest reef system,” said Dr Hoey.

“We need urgent global action on greenhouse emissions to save the world’s coral reefs. Australia should be – but regrettably isn’t – at the forefront of tackling global heating,” said Prof Hughes.

Learn more: A glimmer of hope for the world’s coral reefs

 

 

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Some reef-building corals primed to resist coral bleaching

New research suggests that “robust” corals including brain corals, may be more resilient, to bleaching than “complex” corals such as the branching staghorns. Orpheus Island, Great Barrier Reef. Credit: ARC CoE for Coral Reef Studies/ Tory Chase

A world-first study has revealed that “robust” reef-building corals are the only known organisms in the animal kingdom to make one of the “essential” amino acids, which may make them less susceptible than other corals to global warming.

Using advanced genomic techniques, a team of researchers led by Dr Hua (Emily) Ying of The Australian National University (ANU) and Prof David Miller of the ARC Centre of Excellence for Coral Reef Studies (Coral CoE) at James Cook University (JCU), have found that the group of corals classified as “robust,” which includes a number of the brain corals and mushroom corals, have a key physiological advantage over “complex” corals, including common branching corals such as the staghorn coral.

In a new paper published today in the prestigious journal Genome Biology, the researchers report that “robust” corals possess a unique capacity to generate an “essential” amino acid.

“Amino acids are the building blocks of life,” said lead author Dr Emily Ying of the ANU Research School of Biology.

“They are crucial, for example, in repairing tissue or growing new tissue. But, generating amino acids is energetically costly for animals, so they usually only generate 11 of the 20 required for life.”

“The remaining nine amino acids are called the ‘essential’ amino acids because they must be supplied by the animal’s diet. For corals, this includes tiny drifting animals known as ‘zooplankton.’”

But this is not the only form of sustenance for corals. Through a mutually-beneficial relationship with microalgae known as Symbiodinium, corals are supplied the energy needed to build their hard skeletons.

Symbiodinium also supplies the coral with some of the ‘essential’ amino acids, making them less dependent on their diet than other animals,” said senior author Prof David Miller of Coral CoE at JCU.

For example, when global warming causes corals to bleach, they expel their resident Symbiodinium and are therefore suddenly fully dependent on their diet to meet this nutritional requirement.

“We now know that ‘robust’ corals can make at least one of the ‘essential’ amino acids without relying on Symbiodinium. This suggests that they may be more resilient, at least in the short term, to bleaching than the ‘complex’ corals such as the branching staghorns,” explained Prof Miller.

Until now, scientists had few clues about why some corals only host a specific Symbiodinium type and others are less particular.

“Our research also suggests that ‘robust’ corals are less choosey about which species of microalgae can take up residence in the coral’s tissue. The ability to host a broader range of Symbiodinium types could facilitate more rapid acclimation to higher temperatures,” said Prof Miller.

Learn more: “Robust” corals primed to resist coral bleaching

 

 

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