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The job market for protein biochemists with interdisciplinary savvy is on the upswing For years, proteins took a backseat to dna while the human genome was being sequenced. But now, attention has swung back to proteins. In response, companies that focus on proteomics--large-scale protein analysis--have popped up and are growing fast. These proteomics companies range from companies that manufacture tools for other scientists' use to companies that use proteomics as a platform for their own drug discovery efforts. This article focuses on proteomics companies, but similar positions can be found in large pharmaceutical companies as well.
"Clearly, proteomics has really revitalized the whole area of protein biochemistry," says John W. Kozarich, president and chief executive officer of ActivX Biosciences in La Jolla, Calif. "Molecular biology is still quite important, but I think the chief executive officer of ActivX Biosciences in La Jolla, Calif. "Molecular biology is still quite important, but I think the emergence of proteomics has created a strong desire for getting people who are well trained in protein biochemistry. Those people went through a bit of a slump for a while." Paul F. Predki, vice president of research and development at Protometrix, located in Guilford, Conn., agrees that protein biochemists have been in short supply recently. "It's easier to find molecular biologists than it is to find good protein biochemists, which these days are a combination of the two anyway," Predki claims. "If you work with proteins, the chances are that you've been involved with cloning and expressing them, so you've got a basic molecular biology skill set, too. It can be a challenge to find people with good protein experience, though." PROTEOMICS companies hire a wide variety of scientists. At MDS Proteomics, based in Toronto, the company's scientists include biologists, biochemists, analytical chemists, synthetic and theoretical chemists, mechanical and software engineers, and bioinformaticians, according to Paul McCracken, director for planning and analysis. "It's a constant feedback loop where all the different disciplines are interacting on a regular basis," he remarks. Sussannah Kelly, senior vice president for human resources at MDS Proteomics, says teamwork is especially important. "The behavior of people really matters here. We can't handle huge egos, because [the company] is moving so fast. What has worked so effectively is the atmosphere around teamwork. Silos are not tolerated." MDS Proteomics takes a mass spectrometry approach to proteomics, using the technique to study protein-protein interactions, protein-small molecule interactions, and differential protein expression. Earlier this year, scientists at the company published work in which they used mass spectrometry to identify protein networks in yeast [Nature, 415, 180 (2002); C&EN, Jan. 14, page 6]. Although much of the science centers on this platform, the company does not see itself as a "platform company." Instead the focus is on drug discovery. "It's not like we have built a platform for others to rent," McCracken says. "That's not the strategic vision of the company at all." MDS Proteomics built three of its four major facilities around particular academic scientists, Kelly says. In addition to its Toronto headquarters, which is near the laboratories of Tony Pawson, molecular and cancer biologist at the Samuel Lunenfeld Research Institute, the company also has laboratories in Odense, Denmark, near the labs of Matthias Mann, mass spectrometrist at the University of Southern Denmark, Odense; Charlottesville, Va., near the labs of Donald F. Hunt, mass spectrometrist at the University of Virginia; and Boston. "We have built a capability in mass spectrometry that is second to none," McCracken says. The company has been very fortunate because "good people attract good people and talent attracts talent," Kelly says. ANOTHER COMPANY focusing on proteomics in the Toronto area is Affinium Pharmaceuticals, which started out as Integrative Proteomics but changed its name in February to better reflect what it actually does. Since its founding in August 2000, the company has grown to just over 60 employees, about 90% of whom are scientific rather than administrative. In addition to the type of protein cataloging usually associated with proteomics, Affinium is also studying the "very detailed architecture of individual proteins that are targets of small-molecule therapeutics," says Molly B. Schmid, senior vice president of antibacterial pharmaceuticals and alliances. Affinium uses mass spectrometry, X-ray crystallography, and nuclear magnetic resonance spectroscopy for its work in structure-based drug design. Because of the "remarkable" changes in the field of biology, chemists have a large role to play in proteomics, Schmid says. "The extent to which the field of biology is merging with other fields in ways that haven't been anticipated up to this point is astonishing and happening very quickly," she says. "As time goes on, chemists will be getting training in the biochemistry side of things, mostly because the jobs are there and the science is fantastic." She says that proteomics has room for organic chemists, analytical chemists, materials scientists, theoretical chemists, and even chemical engineers. "Everything we do involves growing cells, growing them efficiently, growing them in high quantities," Schmid says. Microarrays are another approach to proteomics. Protometrix is a start-up company focusing on the development and application of protein microarrays for drug development. The company has developed platforms for molecular interaction analysis and biochemical assays, based on work done in biologist Michael Snyder's lab at Yale University. The company has hired an interdisciplinary team of molecular biologists, biochemists, engineers, chemists, and computer scientists to standardize and industrialize these technologies. Two companies--Ciphergen and LumiCyte, also based in Fremont--combine the protein array approach with mass spectrometry. In their cases, however, the mass spectrometer is used solely as a detector. "We don't really look at ourselves as a mass spectrometry company," Ciphergen's Rubin says. "To us, the mass spectrometer that's integral to the technology is a detector. It's a reader for the ProteinChip Arrays. Our paradigm is to deliver these instruments directly into biology labs. We've taken great pains at making a mass spectrometer so that the instrument itself is very simple to learn to use and to run."
Both companies anticipate using the chips for diagnostic purposes. One of LumiCyte's goals is to create "the world's most comprehensive map of human serum proteins," Hutchens says. "We're interested in discovering the proteins that have immediate clinical utility." To do this, samples are analyzed from different patient groups to find proteins that vary with disease state. "As soon as we have discovered sets of proteins whose presence or absence gives us the pattern that associates with a change in health state, we can use the same type of biochip to enter immediately into a high-throughput assay mode," Hutchens says. "We do not have to rely on one set of technologies or one technology platform to map and discover new proteins and then hope that we can translate that discovery into another format that enables a rapid, low-cost, scalable deployment of that measurement capability." SELDI has recently been demonstrated to be useful for early diagnosis of ovarian cancer [Lancet, 359, 572 (2002); C&EN, Feb. 18, page 13]. The system used in that instance was from Ciphergen. Ciphergen has emphasized hiring scientists who are experts in the field of protein biochemistry, Rubin says. These people, once they learn the SELDI technology, can help further the applications by working directly with clients in the field. Ciphergen calls these individuals field research scientists, all of whom are Ph.D.-level scientists. ActivX, meanwhile, takes a chemical approach to proteomics, focusing on what it calls activity-based proteomics. "We develop chemical reagents that allow one to interrogate large families of proteins that are related by some functional motif or structural motif," Kozarich says. "By doing that, you can go in principle into any tissue, any cell line, any proteome in any species and rapidly get a readout of the functional levels of related proteins." ActivX's methods are based on enzymology and protein biochemistry--revitalized by the new problem of proteomics, Kozarich says. They draw on 40 years' worth of literature about the use of small-molecule probes to unravel protein structure and function. "We take that information and realize that it's sitting there waiting to be reharvested for a new problem," Kozarich says. "We're making these tools to look at a subset of the proteome, but it's a subset that has real pharmaceutical meaning because it's related to the function of proteins." For example, a single chemical tool could be used to probe acetylcholinesterase, thrombin, or a variety of lipases, because they're all serine hydrolases, a protein family with possibly more than 1,000 proteins. Because ActivX's methods rely on the design of new probes, the company employs synthetic chemists. The company is especially interested in "chemists who are interested in working at the interface between their synthetic chemistry skills and proteomics and protein biochemistry to design the types of tools that we need to look at other protein families," Kozarich says. Proteomics is such a broad field that people agree there's no one way in. "We have so many different backgrounds that it's hard to say you need to do X, Y, and Z to prepare," McCracken says. "The type of people who excel here are flexible, curious, and take the initiative." However, people are still willing to offer advice to those who are interested in pursuing careers in proteomics. "I have advised a number of my former students and postdocs to try to learn much more about protein separation science," says Hutchens, who used to be a professor at Baylor College of Medicine, Houston. "After all, if proteomics is anything, it's a practice that starts with the ability to separate proteins." He also advises people to become familiar with software tools and data analysis beyond classical statistics. Predki believes that there are three key components to a good background for proteomics. The first is a good background in protein biochemistry. Second, he thinks that scientists should know how to analyze large data sets. "I don't think that they necessarily need formal training in bioinformatics, but an understanding of how databases work and how to query databases is important," he says. Finally, he believes that people should have applied protein biochemistry techniques to a wide variety of proteins, rather than just a handful. Affinium's Schmid says people who want to go into proteomics should be interested in interdisciplinary careers. "If we hire chemists, the expectation is that even if they walk in the door without very much biological knowledge or language, that they will both want to and will need to acquire that language and understand what we're working on."
In addition, Hutchens points out that it is necessary to want to solve problems at the interface of biology and medicine. "At the end of the day, if you can't solve a problem that is important--and sooner rather than later--then your efforts become more and more esoteric," he says. Growth at these companies is going strong. "As an emerging company, we're in a pretty significant state of growth," says Joanne E. Harack, vice president of human resources at Affinium. "We're engaged in very significant hiring now and will be for the next couple of years." Adding people is also the plan at ActivX. "Our growth plan this year is to continue growing," Kozarich says. "We will probably add another 15 or 20 positions to our current total of 50--perhaps more, depending on the number of our discussions with big companies and how they're proceeding." In the future, Kozarich says, the company will begin to focus on internal discovery programs, requiring a "step-up of commitment to chemistry." Hutchens believes that LumiCyte has created a "critical mass" of talent and doesn't anticipate significant expansion of the scientific staff at this point." We have built an infrastructure that we believe is going to allow us to solve problems and generate revenues, probably without significant expansion over the next two years," he says. The company currently has more than 40 employees. Now, Hutchens says, LumiCyte is more interested in scientists who have an interest in the business aspect. "None of what we do gets into the right hands until we have people who demonstrate utility and articulate that utility to other scientists and physicians. Right now we're building on the business development side," he says. Ciphergen also expects to grow, although Rubin doesn't try to attach a number to his projection. He points out that the company doubled in business last year and says that in "the simplest analysis, you expect to increase staff at a similar pace." The company currently has around 250 employees. Predki declines to place a number on Protometrix' current size. However, he points out that the company was founded just last September. "We've grown at a reasonably rapid rate," he says. "We're nearing the end of what I would consider our first round of hiring. We're a typical size for a company this old." That first round focused on the people, including computer scientists, needed to transfer the company's technology from Snyder's lab at Yale. The company's bench scientists include a mixture of technicians and Ph.D.-level scientists in molecular biology and protein biochemistry. "As we grow, we're going to be paying attention not so much to the generation of data or information but the analysis and utility of it," Predki says. "We'll be looking more for discovery scientists and people with drug development experience." Proteomics is an emerging field that's likely to be around for a while, Schmid says. "It's really what molecular biology in the larger sense is morphing into and, on the other side, what chemistry is extending to. The whole field is really merging the sciences in a way that hasn't happened up to this point." |
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