Proteomics Feature: How a word helped a science to take off

You can't pick up a general article about proteomics without reading somewhere in the story: "The word 'proteomics' was coined by Marc Wilkins, then a PhD student in Keith Williams' lab at Macquarie University in 1994..."

But the story goes further than that, of course. Wilkins' involvement with proteomics substantially mirrors the development of the science in Australia.

Eight years after coining that word, Wilkins still works with the same team, now the team at Sydney company Proteome Systems.

Like all good science stories, this one might have been quite different had Wilkins chosen a different path. "The late '80s was the age of molecular biology," he says. "But after my honours, I was at ANU doing sequencing, and it wasn't as exciting as you'd expect!"

One catalyst for his renewed interest in protein science was attending a seminar by Swiss scientist Denis Hochstrasser, who showed the young scientist that protein research could be as dynamic and exciting as genomics.

"This guy probably was the first of the European group who started to get this science to really sing," Wilkins says. "This was a revelation to us. What the genomics guys were trying to do, you could do with proteins." Under his professor, Keith Williams, Wilkins and his postgrad colleagues began to bring separation and analysis technology with high-throughput amino acid analysis.

"It was the fastest means of identifying proteins at the time," Wilkins says. "In 93-94, mass spectrometry hadn't really taken off. The thing that was exciting was that these things together might be creating a new area of science."

What it lacked was a name to do away with "all the awkward phrases" that the researchers wanted to convey.

"Origins of words always fascinated me," Wilkins said. "It had to be something like 'protein' and 'genome'. I wanted to come up with a word which made sense to anyone who saw it, that rolled off the tongue." Wilkins first used his new word, 'proteome' at a conference in Italy in 1994 and it quickly took off.

"The nice thing was that we kind of got the concept out in '94, a year before the first genome sequence was published," Wilkins says. "The timing was perfect; the functional genomics era was just beginning, and the term struck a chord" - partly, Wilkins says, "with frustrated biochemists who wanted to explain what they were doing".

The rise of proteomics has been simultaneous - not coincidental - with massive changes in the way biologists work.

Gone are the days, Wilkins says, when a researcher could submit a protein sequence to a journal and get a publication out of it. Now, protein maps are beginning to spring up in research literature, tagging individual proteins to identify vast swathes of new possibilities in the study of disease.

After his PhD, Wilkins went to Geneva for two years to work with Hochstrasser and Amos Bairoch, the two pioneers in developing protein information banks. Meanwhile, Wilkins co-edited the first book about proteome research.

The Geneva experience was "remarkable", Wilkins says, but things were happening back home - his former colleagues at Macquarie were talking about spinning off a company - Proteome Systems - and commercialising their research.

Anyone who did the old, slogging kind of protein research, Wilkins says, "enjoys a challenge", and being part of a start-up is "not for the faint-hearted".

Now head of the company's bioinformatics division, Wilkins and his team have developed a suite of databases and tools.

"Biology is now fundamentally an information science, and we're working very hard at making this happen," he says.

Wilkins says he'd probably find academe somewhat dull after the start-up experience.

"Here, you're using your wits to look at an area scientifically and think about the commercial opportunities," he says. "The challenges are very real and the environment here is extremely fast-paced. All of us who were founders recognise that this is a rare opportunity - the ability to bring in as highly talented group of people who all pull together, in an area that is just taking off - the opportunities are really remarkable."

Proteomics for dummies

Proteomics is complicated science. So how to you explain it to a lay audience?

Proteome Systems CEO Keith Williams has had plenty of practice at pitching proteomics to everyone from venture capitalists to governments to the IT sector.

At IBM's recent Focus conference in Sydney, he explained to the entirely non-scientific audience that "when you take the water out of you, half of what's left are proteins. The other half is sugars and fats, and proteins create the sugars and fats.

"Try to understand the monstrously complex interactions within cells, and then between cells. A DNA sequence gives you the parts manual, but doesn't tell you how to assemble it.

"Imagine you took Sydney and broke it up into its component parts - every shopfront, every street sign -- and put it into the desert and said 'now go and build Sydney' - you're starting to see the problem. "Very little is understood about the different parts of the cell, and how it fits together.

"Proteins give you an insight into more general issues of how we're going to have to approach biology. Proteins are the functional units. Those that are defective cause disease.

"The context is that current medicine acts on about 20 per cent of actual known molecules. Think about taking your car to get serviced, and the mechanic knows one in every five parts.

"There are about a million different protein molecules that need to be understood. The instruments we're using are producing terabytes of data, which is scary stuff."

New era for the original proteomics facility

In 1996, the establishment of the Australian Proteome Analysis Facility (APAF) at Macquarie University made it the first of its kind in the world.

Six years later, how is it looking? The answer, according to its director, Prof Gary Cobon, is that APAF is about to enter a new era.

Still the only facility in Australia that is capable of industrial-strength high-throughput protein screening, APAF has received upgraded Major National Research Facility funding to allow it to establish complementary facilities in Adelaide and at the universities of Sydney and NSW.

APAF's main focus is on contract research, and it has established about 200 collaborations, Cobon says, including 30 internationally. Multinationals Schering-Plough and Aventis are among its clients, and it has a growing list of clients from south-east Asia.

"We're well ahead of the rest," Cobon said. "I think we've got quite a reputation."

One reason for that was the fact that APAF was such an early player in the field. "During the MNRF interview, I did say that the Australian government needs to be congratulated for being so far-sighted," as did the "enthusiasm and entrepreneurship" of APAF pioneers Keith Williams and Ian Humphery-Smith, Cobon said.

However, concentrating on contract research has a price, Cobon said - "we haven't been able to do much fundamental research, and some of our equipment is getting a bit long in the tooth."

However, the new funding injection will remedy that, and Macquarie has committed itself to supporting ongoing fundamental research in proteomics - recently, the university advertised for a chair in proteomics. "That will be of great assistance to us," Cobon said.

From its small beginnings, APAF now has 15 staff of its own, and visitors - some of whom stay at the centre for two years - boost the number to more than 30.

Collaborations have always been important to the facility. One of its earliest relationships was with instrument company Bio-Rad, which went on to develop the first suite of proteomics instrumentation. And as Macquarie develops new technology to aid its research, Cobon says, APAF will have first right of refusal.

All up, APAF is due for about $50 million in funding from the Commonwealth, NSW and South Australian governments over the next five years.

An Australian proteomics map

By Pete Young

Australia's performance and prestige in protein science research has been uniformly high since the 1960's when the legendary medical scientist Pehr Edman built the world's first automated protein analyser at St Vincent's Hospital in Melbourne.

In recent times, a generational change has been underway in Australian proteomics. The rising new wave of research leaders may face funding challenges in building and maintaining strong support teams.

A short, non-exhaustive list of companies, institutes and researchers currently in the forefront of Australian proteomics work and set down in no particular order would include:

• Joint Protein Structure Laboratory - headed by Prof Richard Simpson, this is a partnership between the Ludwig Institute for Cancer Research and the Walter and Eliza Hall Institute of Medical Research. Its focus is on analytical biochemistry and technical developments in protein separation and characterisation as well as proteomics.
• Australian Proteome Analysis Facility -- Established at Macquarie University in 1995 as the first dedicated proteome centre in the world.
• St Vincent's Institute of Medical Research -- Deputy director and Max Planck Award for Biology winner Bruce Kemp has the rare attribute of having a peptide named after him.
• Baker Medical Research Institute - Specialises in cardiovascular research and the identification and characterisation of proteins responsible for cardiovascular disease. One of its leading identities is Dr Ian Smith.
• Australian Wine Research Institute - A South Australian centre of proteomics activity led by director Prof Peter Hoj.
• Protein Facility, University of Western Australia - Protein analysis and peptide synthesis. Its director, Dr Richard Lipscombe is a protein chemist and a leading expert in mass spectrometry for protein analysis.
• Institute for Molecular Bioscience - This Queensland centre has a a number of well-known proteomics researchers associated with it, including Prof John Mattick and Prof Paul Alewood.
• University of Sydney and University of NSW - Both boast structural biology units at the cutting edge of proteomics research.

On the commercial side, a number of companies operate in the proteomics zone. Most but not all develop and market devices or instruments used by proteomics researchers. Among the better known are:

• Proteome Systems - Its revenues are balanced between device products and drug discovery work. Axon Instruments - Micro-array scanners are in its product line. Headquartered in California, it has an engineering department in Melbourne.
• Vision BioSystems - Long-standing manufacturer of lab instruments, it is a division of publicly-listed Victorian company Vision Systems.
• Gradipore - Sydney-based Gradipore develops and markets separation technologies for the life sciences market, and blood clotting tests for genetic disorders for the health industry.
• Peptech - A listed company, it develops and commercialises human therapeutic proteins.