Microbiologist to the stars

Professor Malcolm Walter has been making a name for himself for decades, poking around amongst the fossilised stromatolites found in the Pilbara in WA and finding out just how long life has existed on Earth. He still does this but has turned much of his attention to Mars, where he hopes that his findings about early microbial life on Earth will help find life elsewhere in the universe.

While Walter looks at the fossil stromatolites, the oldest of which have been pinpointed at 3.43 billion years, Professor Brett Neilan and his colleagues look at the living ones. At the relocated ACA, a multidisciplinary team has now been formed involving biologists, geologists, palaeontologists, physicists and astronomers. At the official launch in late May, the guest of honour, astronaut Dr Andy Thomas, said the centre will help to answer some of the most profoundly important questions about how life began on this planet.

“I can think of little more important question than that as we, one species of this immense universe, should strive to answer,” Thomas said. “It will affect the understanding of ourselves, it would dramatically change our culture, our communities, our philosophy, our religion and the way we grow as people. It would be a step towards bringing us closer to that essential truth that is so often pursued by poets.”

While Brett Neilan, the ACA’s deputy director, is unsure of exactly what he is – geneticist, micro or molecular biologist, environmental scientist, favourite of graduate students – he is probably not a poet. What he does know a lot about is cyanobacteria, research that has seen him awarded a Eureka Prize for research in 2001, the Fenner Medal from the Australian Academy of Science in 2004; another Eureka Prize, this time with Walter and Brendan Burns, in 2005; and last year’s Australian Society of Microbiology Frank Fenner Award, for which he delivered the ASM Fenner Lecture recently.

It has also scored him several ARC grants and, earlier this year, a much-sought after Federation Fellowship, part of which he will use to send some of his PhD students to extreme environments in search of bacteria.

Cyanobacteria are the ubiquitous, ancient and potentially deadly prokaryotes that not only produce much of the oxygen that we breathe and form stromatolites but which also have a habit of fouling up our waterways and causing toxic damage to animals and humans.

Neilan has been able to track down the genetic signature of several of these toxins and has helped develop diagnostic kits to discover which one is responsible when an algal bloom breaks out. This knowledge, predominantly concerned with the toxins produced by freshwater cyanobacteria but which is moving into marine toxins, not only has huge environmental and safety importance but is also being applied to pharmacology and drug development.

An understanding of cyanobacteria will also help if – or when – life is found on other planets. As the ACA was being officially opened, NASA’s Mars Lander touched down, armed with a shovel and the mission of digging for ice. If water is there, bacteria or some other microbe might be there, something that Malcolm Walter is rather keen on finding out.

He is a member of an international group planning the first two-way mission to Mars, sometime after 2018, which aims to return samples to Earth. “If there is life out there it is most likely to be microbial,” he says.

---PB--- Back on Earth

Brett Neilan didn’t start out as a microbiologist, and he still jokes that he isn’t one, as he can’t tell the difference between Gram positive and negative bacteria. He actually started out in human genetics, having the good fortune to work with the likes of Bob Symons, discoverer of ribozymes, at the University of Adelaide in the mid-80s. That was at the start of the revolution in molecular biology and genetic engineering, when new techniques were coming on stream that allowed him to learn molecular biology from the ground up.

A period in forensic biology followed – “but I didn’t like working with dead people”, he says – and then more fortune in joining John Shine’s team at the Garvan Institute in Sydney, where he worked on the follicle stimulating hormone. Everyone else seemed to be getting a PhD so he moved to the Prince of Wales Hospital and began work on the genetics of spinal muscular atrophy.

“In another lucky step I got out of that just before the human genome came out, so I wouldn’t have been the first to find that gene,” he says. “I was offered to change my PhD up at UNSW in microbiology – it was a project funded by Sydney Water back in those days and that was to look at the genetics of blue-green algae. I saw an ad down at Lorne, thought it sounded interesting and it is still all the same day to day bench work – when you get DNA from a human or a bacteria it’s not much different.

“Back then there were a lot of people doing PCR for human genetic diagnosis for prenatal diseases and things like that, but there was very little being done in the field of microbiology and genetic testing. I thought this could be an interesting way of getting my PhD done quickly and out of the way. I was applying the techniques I’d learned (in human genetics) to an area that it wasn’t much being done in.

“Today, environmental microbiology is one of the biggest users of genomic and proteomic technologies around, discovering all of these new things that we never thought lived on Earth.”

Two post-docs followed – one in astrobiology at Stanford University, where he worked in the geology department and got to go exploring, and the other in the biochemistry of toxin molecule analysis at Humboldt University in Berlin. It was in the latter area that he was awarded an ARC fellowship and returned to Australia.

During his stay in Berlin he was part of a team that discovered the first gene for the toxin microcystin, found in Microcystis aeruginosa, the most common of the hepatoxins produced by cyanobacteria and the most responsible for poisoning animals and humans. Genes and gene clusters have since been found for nodularin, produced by Nodularia spumigena, and work is ongoing on cylindrospermopsin and saxitoxin, produced by Cylindrospermopsis raciborskii and Anabaena circinalis, other cyanobacteria.

Neilan and his colleagues have developed and patented real-time quantitative PCR analysis for these toxins, and regularly carry out molecular testing for Sydney Water and the Sydney Catchment Authority when a bloom strikes. The team is working with Sydney company Diagnostic Technologies to develop a diagnostic kit.

While algal blooms are a big problem for clean water supplies, particularly in Africa, China and Europe, they are rather interesting from another aspect that Neilan and his team are researching. Naturally produced toxins are being studied throughout the world for their potential in human therapeutics, and the toxins from cyanobacteria are no different. As many of the toxins produced by cyanobacteria affect hepatocytes, research is being done into how the toxin molecule is transported to the liver, with the future potential of harnessing the pathway to deliver drugs.

One of Neilan’s PhD students, Alex Roberts, is looking at the transposase associated with the genes that produce the toxins and how it rearranges genes to produce new types or more or less potent toxins. This transposition-type recombination could potentially move genes from a toxic species into a non-toxic species, proving a problem in the future, but it could also be useful in developing new compounds such as immunosuppressants.

This is work Neilan’s team is actively pursuing, in addition to using molecular probes developed to detect toxic species in water to find antibiotic-producing bacteria and bacteria that can produce immunosuppressive molecules.

---PB--- Extreme environments

Back in WA, where Neilan has directed studies on extant stromatolites, as opposed to the fossils so well-documented by Walter and his colleagues, research is ongoing into an understanding of cyanobacteria and their survival and proliferation in extreme environments, such as the hypersaline environment of Shark Bay. Recent research by his team has found that the Shark Bay have remarkable biodiversity, with evidence so far of more than 100 species of bacteria.

"In effect, this suggests that by 3.5 billion years ago Earth was already teeming with diverse microbial life,” Neilan says. “If this is so, evolution must have already been going on for a long time. We can't be sure, but certainly many tens of millions of years earlier. These findings could reset the start of the clock of life."

Neilan visits the area regularly, has taken trips to Antarctica and is planning a trip to Indonesia later in the year to sample a volcano. (He jokes that he prefers to leave the prospecting in the more difficult environments to PhD students these days, reserving for himself the pleasures of field work in more conducive environments such as the tropical Lizard Island, just off Cairns.)

“The theory is that we haven’t explored these environments for their biodiversity. There is a huge amount of biodiversity in Australia and Shark Bay is one example of that. People have explored the desert and think it has no life but if you take a sample there’s a huge amount of fungus and bacteria living in that dry sand. We do any type of environment that hasn’t been studied extensively.

“That’s the fun bit – you can plan an adventure holiday and then do that for about two or three weeks a year and then for the rest of the time you sit in a fluorescent light pipetting.”

The very welcome Federation Fellowship will allow him to add a few more PhD students and post-docs – even perhaps the luxury of an administrative assistant – and to expand his research into other toxin-producing organisms, as well as a project to conduct a metagenetic analysis of Shark Bay’s stromatolites.

“One of the main avenues we will move into now is to look at marine toxins. We’ve done the freshwater and now there’s the toxins like ciguatera, the fish poisoning toxin, and then red tide-type toxins, which again is related to a cyanobacteria-type toxin called saxitoxin. Also tetrodoxin, found in fugu and blue-ringed octopus. Once again I’ll send the students out to collect that.”

While the students might be in mortal danger, they will learn something, and with the ACA one of the few international partners of the NASA Astrobiology Institute, the future prospects are appealing, if one of Malcolm Walter’s former PhD students, Abby Allwood, is anything to go by.

Allwood is a geologist who co-wrote a ground-breaking paper in Nature in June 2006 with Walter, dating some of the Pilbara stromatolites back to 3.43 billion years ago and adding more weight to the argument that the fossil stromatolites were formed by biological processes and not by geological or chemical reactions. She is now working at NASA’s Jet Propulsion Laboratory in Pasadena, while another of Walter’s former students, Adrian Brown, is working at the Search for Extra-Terrestrial Intelligence (SETI) Institute in Silicon Valley.

“It’s multi-disciplinary, this astrobiology – physics, chemistry, biology and geology,” Neilan says. “One reason I’m interested in it is that it’s such a great recruitment tool to get students back into university doing science, any of those sciences, and we want to design it so that they get a mix of all of them during their three years.”