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Globe-trotting Humphery-Smith Promotes Proteomics With Charm

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AT A GLANCE

Name: Ian Humphery-Smith

Position: Chief Operating Officer, Glaucus Proteomics, and Founding Chair, Department of Pharmaceutical Proteomics, University of Utrecht, Netherlands

Prior Experience: Developed robotics for excising 2D gel spots; helped establish the Australian Proteomics Analysis Facility; led the founding of HUPO

Seven or eight years ago, when it became clear that proteomics had the potential to emerge from protein biochemistry as its own distinct discipline, a few scientists took the lead in promoting the field and laying out a vision for what proteomics might accomplish. With his rapid-fire speech and emphatic but friendly manner, Ian Humphery-Smith is one of these visionaries.

Schooled as an undergraduate in zoology and parasitology at the University of Queensland in Brisbane, Australia, Humphery-Smith said he spent much of his time as a graduate researcher “studying lots of little animalcules” as Anton van Leeuwenhoek referred to parasites, bacteria, and viruses in the late 17th century. He took a fancy to the evolution of host-parasite relationships, and took a postdoc in 1984 at the Commonwealth Scientific and Industrial Research Organization, an Australian public/private research institute, where he studied the viruses that infected tourists in the Coral Sea.

From the Coral Sea, Humphery-Smith turned his attention to the Atlantic Ocean, moving to a medical school in western France to study the closest living relatives of the exotic viruses he had studied off the coast of Australia. But the jump to France was not purely due to scientific interests — or the desire to travel. Several years earlier, during his years in graduate school, Humphery-Smith had spent a year in Paris studying worms found in the guts of marsupials, and while in Paris he had also met his future wife. “We are but pawns to the winds of our hearts,” he said as a partial explanation for his return to France.

While a postdoc in France, Humphery-Smith shifted his research to the study of mycoplasmas found in mosquitoes, as a potential mechanism for controlling malaria. Through this work, he began using 2D gels to study the organism Mycoplasma genitalium, and soon came into contact with other European groups developing systems for imaging and analyzing gels, including Denis Hochstrasser’s group at Geneva University Hospital. When Humphery-Smith returned to Australia in 1992 to take a job at the Australian National Genomic Information Service, an organization connected with the University of Sydney, he helped arrange for Hochstrasser to spend three months with Keith Williams’ group at Macquarie University, where Hochstrasser disseminated his expertise on 2D gels. It was about this time that Marc Wilkins, a member of Williams’ lab, dreamt up the term “proteome.”

Meanwhile, Humphery-Smith, along with Williams and others, began lobbying the Australian government for money to establish a contract research and technology development center focused on proteomics. In late 1995, the group received $3.7 million in start-up funds, and the Australian Proteome Analysis Facility (APAF) was born. Williams went on to take leadership of APAF, while Humphery-Smith launched a separate proteomics facility at the National Innovation Centre in Sydney with three years’ worth of funding from Glaxo Wellcome that he had received earlier that year.

But Australia was a little too remote even for Glaxo Wellcome, Humphery-Smith said, and at the end of the three years Humphery-Smith packed up his 2D gel technology and moved it to Stevenage, UK. One of the first robots they built “was about the size of your local bathroom,” Humphery-Smith said, and used a $120,000 CO2 impact laser excision unit, a technology that hasn’t been used since because of its cost. Although the interaction with Glaxo Wellcome was fruitful in terms of technology development, he said, they didn’t learn any more about Mycoplasma genitalium than they had by hand because “whenever we put these low abundance proteins into 96-well plates, all the proteins adsorbed to the plastic.”

To try to address this problem, Humphery-Smith formed Glaucus Proteomics, initially based in Australia, to try to develop and commercialize technology for cloning genes and expressing proteins, producing antibodies to the proteins, and arraying the proteins and antibodies on microarrays. Humphery-Smith also teamed up with Biotul, a German biotechnology company developing polymer and hydrogel surface chemistries for use with arrays, and after the company ran into financial difficulties, Glaucus acquired most of Biotul’s intellectual property.

Humphery-Smith solved the question of where to locate Glaucus — Australia being out of the question—when he accepted an offer in August 1999 to become the founding chair of the pharmaceutical proteomics department at the University of Utrecht, in the Netherlands. As part of its relationship with Glaucus, the university was able to “spin-in” some of its technology, in return for providing Glaucus with access to the university’s infrastructure, Humphery-Smith said.

Today, Humphery-Smith is busy refining Glaucus’ technology for expressing human recombinant proteins in E. coli — he said the company can now express and purify 1,000 recombinant proteins in one month — as well as working with Medarex and GenMab to produce high quality antibodies against those proteins for use in antibody arrays. The company is currently looking for pharma and biotech companies to become early-access partners, but he admitted the onus is on the makers of protein microarrays to show how researchers would use the arrays. “Applications are what we and others must demonstrate to the marketplace,” he said.

In addition to his work with Glaucus, Humphery-Smith also took the initiative to recruit members and found HUPO, the year-old organization devoted to promoting and coordinating proteomics research activities across the globe. Although Sam Hanash of the University of Michigan has taken over the reins as president of the organization, Humpery-Smith remains involved by leading the group’s fund-raising efforts. “That was a thing I think was important to do for the discipline,” he said. “Just as we had a Human Genome Project, there’s a need for both the private and public sectors to take the human proteome project seriously.”

—JSM

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