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Chemistry’s Liaisons

Chemical biologists bridge the divide between two fields

by Sophie L. Rovner
March 19, 2012 | APPEARED IN VOLUME 90, ISSUE 12

Credit: Dana Thomas
Will Beavers, one of Marnett’s grad students at Vanderbilt Institute of Chemical Biology, uses a mass spectrometer.
Credit: Dana Thomas
Will Beavers, one of Marnett’s grad students at Vanderbilt Institute of Chemical Biology, uses a mass spectrometer.

Spend any time at all with chemical biologists, and you’re likely to want to join their ranks. These researchers—who use chemical tools to understand biological systems, or who study the chemical reactions that take place in living organisms—are an enthusiastic bunch. And because their field is relatively young and is broad in scope, it offers appealing opportunities for chemists who want to blaze a new trail in science.

Credit: Kyle Werder
Balskus has just launched her academic career as a Harvard professor.
Credit: Kyle Werder
Balskus has just launched her academic career as a Harvard professor.

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Chemical biologists apply the logical and intellectually satisfying tools and concepts of chemistry to fundamental and interesting problems in biology, says Lawrence J. Marnett, director of Vanderbilt Institute of Chemical Biology, by way of explaining the field’s hold on its practitioners. “In addition to creating new knowledge by interrogating biological function,” he says, “there’s always the potential for the use of that knowledge to create new drugs or diagnostic tests to improve human health.” Marnett, who is also a professor of cancer research, of biochemistry, and of chemistry at Vanderbilt University, studies the relationship between inflammation and cancer and uses that information to improve the detection and treatment of the disease.

Chemical biologists can apply their talents to a wide range of challenges. Some work in small-molecule screening and optimization for chemical probe or early-stage drug discovery, Marnett says. Others work on natural product biosynthesis and chemical modification to generate biologically active compounds with novel scaffolds, he adds. Many chemical biologists use high-throughput analytical chemistry in fields such as metabolomics and proteomics, which often rely heavily on mass spectrometry.

The work of Emily P. Balskus is representative of the wide-ranging scope of the field. She became an assistant professor of chemistry and chemical biology at Harvard University this past summer. In addition to establishing her research group, she is teaching a course she designed that examines the chemical aspects of natural product biosynthesis, biocatalysis, and metabolic engineering.

In the lab, Balskus and her team are unearthing new biosynthetic pathways and metabolic activities associated with microorganisms, including human symbiotic microbes, and their impact on health. They are also scouting along those pathways for enzymes that could be useful for organic synthesis.

Balskus has found that the field’s breadth stimulates interactions with colleagues in Harvard’s chemistry and biology departments as well as its medical school. “The boundaries of defined departments are starting to become a little more fuzzy as science gets more interdisciplinary,” she notes, and “working at the interface is a great place to be. People in multiple disciplines can appreciate what you do.”

The same cross-fertilization occurs in industry, whether a chemical biologist is working at a biotech company, a biofuels firm, a contract research organization, or a traditional pharmaceutical company. On drug discovery teams, for instance, “a very natural collaboration happens” between members, who come from several different backgrounds, says Nicola J. Clegg, an oncology research project manager at Novartis Institutes for BioMedical Research, in Emeryville, Calif. “I think a chemical biologist is valued there because they’re able to talk across those disciplines.”

Start-up companies are particularly likely to make good use of the assorted talents of chemical biologists. “A start-up often needs people with multiple skills, because the company doesn’t have the luxury of having a lot of employees,” Clegg says.

Whatever route they follow, these chemists have to face the realities of an economy still recovering from recession. “In general, the job market is very tough for scientists,” points out Ronen Marmorstein, a professor and leader of the Gene Expression & Regulation Program at Wistar Institute, a private cancer research institute located on the campus of the University of Pennsylvania. But “being in chemical biology increases your chances, because it’s a new and upcoming and exciting field,” says Marmorstein, who also holds a joint appointment as an adjunct professor of chemistry, biochemistry, and biophysics at Penn. “A lot of departments are trying to hire more chemical biologists to build up that strength, and a lot of [companies are] also interested in chemical biologists.”

One reason that chemical biology may be suffering less than other fields, Marmorstein adds, is its potential for developing therapeutic compounds, an application he says the government is increasingly backing with funding. “Chemical biology provides some novel and interesting strategies toward developing new and effective therapeutic reagents,” he explains. “There are new tools for creating small-molecule inhibitors and drugs, and there are new chemical biology tools for identifying new protein targets to go after for therapy.”

Vanderbilt’s Marnett, in contrast, thinks that job prospects for chemical biologists are about the same as those for other chemists. But he believes several faculty positions will open up over the next 20 years as the stock market improves and professors who are currently in their 50s to 70s retire.

In the meantime, finding a job requires perseverance and flexibility. In Marnett’s lab, postdocs are staying an extra year to bulk up their curricula vitae so they can be more competitive. They’re also considering nontraditional jobs outside the lab. One of his postdocs went the regulatory route by joining the Food & Drug Administration, and another postdoc is applying for a job as a congressional fellow.

In fact, for chemical biologists who want to move away from the lab bench, “there are plenty of options at the interface where communication or collaboration needs to be facilitated,” Clegg points out. “I’m in one category of that: I’m a project manager in research. I work with a team of biologists and chemists and protein engineers.”

Other chemical biologists are employed in technology transfer or intellectual property positions—or in sales. Chris McGee chose this path, though it wasn’t easy. While earning his Ph.D. in organic chemistry and chemical biology at the University of California, Irvine, in 2010, McGee realized he liked teaching better than life in the lab. He became an instructor for The Princeton Review, teaching organic chemistry to premed students preparing for the MCAT exam.

While looking for a full-time job after graduation, he spotted a recruiter’s ad for an opening at a Swiss company that produces peptides and other complex small molecules as active pharmaceutical ingredients. “I sent in a résumé, and never heard anything back, which was the usual story,” recalls McGee, who estimates he submitted at least 150 résumés during his job search. Eight months later, another position was open at the company, so he reapplied and got the job last March—18 months after he started looking.

McGee is based in Torrance, Calif., but travels extensively for his job as a manager for the firm’s new chemical entity market segment. He visits emerging biotech and pharma companies to identify products they’re working on that his company could help manufacture. “I use chemistry as a way in to understand what they’re doing and identify who I should be talking to,” McGee explains. “I like the interaction with other people, hearing what they’re doing, explaining what we can do.”

McGee limited his job hunt to positions that required a Ph.D. “You work hard for it, and you want to try and use it,” he explains. In hindsight, he believes the restriction limited his search unnecessarily.

In other advice for students interested in a chemical biology career, McGee recommends that they obtain “a really good foundation in organic chemistry and then build biology on top of that.” He also suggests they find departments with a chemical biology curriculum, rather than “going off to graduate school to do chemistry and then read biology on the side.”

Credit: Novartis
Clegg advises chemical biologists to find a niche.
Credit: Novartis
Clegg advises chemical biologists to find a niche.

Clegg benefited from this type of program at the University of California, San Francisco. There, she synthesized compounds to investigate estrogen receptor signaling. She graduated with a Ph.D. in chemistry and chemical biology in 2004. During a subsequent five-year stint as a postdoc with Charles L. Sawyers, she picked up genetic and molecular biological techniques while studying androgen receptor signaling related to prostate cancer—first at UCLA, and then, when the lab relocated, at Memorial Sloan-Kettering Cancer Center in New York City. Her chemistry background facilitated the group’s collaboration with a UCLA chemistry lab that was developing potential therapeutics to inhibit the receptor, and later with the synthetic chemistry facility at MSKCC that was developing methods for scale-up.

During her time at MSKCC, she essentially managed the transition of one of the compounds through preclinical studies in collaboration with pharmacologists, analytical chemists, synthetic chemists, pharmacists, and clinicians. She then helped the lab partner with a biotech company that is now testing the drug in Phase I/II clinical trials. After an eight-month job search, she took up her current position managing cancer research projects at Novartis in 2011.

Credit: Genentech
As a recruiter at Genentech, Tang can offer guidance to job seekers.
Credit: Genentech
As a recruiter at Genentech, Tang can offer guidance to job seekers.

Clegg, like many in the field, acquired a lot of skills along the way. But as they prepare for the working world, chemical biologists need to guard against “superficial training in everything,” she says. “One challenge that a chemical biologist may have is trying to find his or her niche. As a chemical biology graduate, you might end up being a jack-of-all-trades and a master of none. If you haven’t gone into enough detail in one of the disciplines, you’re not sure how to market yourself.”

At the same time, Shawn Tang, a principal staffing consultant for Genentech’s Research and early development divisions in South San Francisco, recommends that students who are finishing up their graduate studies or contemplating a postdoc position obtain a wide range of training, including experience with automation and informatics.

“That could make them more marketable than someone who knows one thing and one thing only,” she says.

Candidates who apply to Genentech typically have completed a two- to three-year postdoc in which they have designed and completed an independent project. The company employs chemists with a biological bent, including chemical biologists, on teams that tackle oncology, inflammation, and central nervous system disorders. Genentech hired quite a few biofocused chemists in recent years because of good growth in its small-molecule division, Tang says. Unfortunately that means the company has fewer openings available this year.

No matter where they apply for work, Tang recommends that job candidates invest some time in polishing their curricula vitae. “Make sure it’s clean, it’s precise, it’s concise,” she says. Rather than cramming every activity into the document, it’s best to highlight the most significant information. For instance, full journal articles should be listed separately from presentations at conferences, which carry less weight.

Chemical biologists who are looking for a job need to be able to communicate their science and explain why it’s important, including the big picture, Harvard’s Balskus advises. They can practice by explaining their work to graduate students who aren’t in the chemistry program. Balskus makes sure the students in her lab have opportunities to present their work at venues outside of group meetings. The university helps by providing several informal settings, including journal clubs, where students can give presentations to broader audiences.

Presenting talks has another benefit: The exposure helps postdocs become known by potential employers, Marmorstein says.

Candidates who are looking for their first job can also utilize the network of contacts they’ve established during their training. Clegg says Sawyers and other mentors were critical to the success of her own job search. “None of the jobs I applied to blindly online led to anything,” she says. “Only the ones where my adviser was able to make an introduction for me led to interesting possibilities.”

Job seekers should also take advantage of social media including LinkedIn and Facebook, Tang says. Genentech posts frequent updates on its Facebook page. Both Genentech and Novartis utilize LinkedIn pages, and their recruiters also comb these sites for profiles of potential candidates. Recruiters at both companies have profiles on LinkedIn, and scientists are welcome to reach out to the recruiters for advice and networking, even if they aren’t currently on the job market.

Regardless of the path they take, the field’s practitioners appear to feel a calling to their work. As Vanderbilt’s Marnett puts it: “When we interview incoming graduate students, they say, ‘I really love chemistry and I want to keep doing chemistry, but I want to do something useful with it. I want to make a difference. I want to help people.’ And chemical biology is perfect for that.”



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