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Getting Ready for Synthetic Biology


Since the completion of the Human Genome Project in 2003, scientists have expanded their knowledge of how living cells work with new approaches including genomics, proteomics, and systems biology. Yet it is another development--the ability not only to understand but also to synthesize genes at a speed and cost unthinkable just a few years ago--that has spurred, arguably, the greatest paradigm shift in recent biology: Today, many scientists are not content merely to analyze and understand life. They want to create it.

Synthetic biology, the synthesis of biological components and devices and the redesign or creation of new life forms, has enormous potential. John Glass, a senior microbiologist in the synthetic biology group at the J. Craig Venter Institute in Rockville, Maryland, puts it this way: If you can imagine a set of genes that will program a cell to do something--anything--then you can make them "at a reasonable cost and test your hypothesis … so it will be possible to attempt to design organisms that have extraordinary properties to solve human needs." 

Today, synthetic biology is still in its infancy. The job market and the availability of training opportunities reflect the field's immaturity. But the field is growing and opportunities are emerging for talented scientists with an interdisciplinary focus who are willing to look at things in new ways. If you're willing to make a commitment, "you can really make a difference," says Natalio Krasnogor, a computer scientist at the University of Nottingham in the United Kingdom.

A Multidisciplinary Approach to Life

Brooke Dill, JCVI
John Glass

Synthetic biology enables researchers to tackle a huge and diverse range of applied problems: building a cell with the smallest possible genome; synthesizing proteins with extra amino acids--more than the 20 found in nature; using bacteria to produce medicines previously too complex to synthesize; even decomposing living organisms into standard, off-the-shelf 'biobricks' that can be assembled on demand.

These diverse projects share a basic principle: they all rely on the synthesis or manipulation of chunks of DNA much larger than those assembled in old-fashioned genetic engineering. The field draws on a combination of existing disciplines, each contributing a unique perspective. Synthetic biologists come predominantly from biology and engineering, but they also come from chemistry, physics, mathematics, and computer science.

At least as important as the field you come from is a willingness to meet other disciplines halfway. "On the one hand, you need basic engineering skills, which involve things like computing [and] modeling of systems." That means you'll need to know some math, says Richard Kitney, a biomedical systems engineer who teaches synthetic biology at Imperial College London (ICL) in the United Kingdom. "On the other hand, you need to have the skills to be able to work in a molecular biology-type laboratory."

Even within biology, you'll need several sets of skills. It's "always useful to have two sets of knowledge: broad molecular skills" and specialized knowledge in the areas of biology you want to apply synthetic biology to, Glass says. "So if you are interested in using the tools of synthetic biology to create new pharmaceuticals, then you need to have an idea of how ... eukaryotes use pathways to create complicated molecules. If your interest is in bioenergy, then you need to understand photosynthesis." Systems biology, biochemistry, synthetic chemistry, microbiology, and enzymology, along with evolutionary, bioinformatics, and biocomputational tools may also all be the cornerstone of your work, depending on the specific field you're working in. "You truly have to be a jack of all trades," Glass says.

Above all, synthetic biology "requires a new way of thinking about biology: the idea that cells are machines and they can be rebuilt the way that electrical engineers now design circuits [and] instruments," Glass says.

A Field in Synthesis

Courtesy, Andrés Moya
Andrés Moya

Synthetic biology started crystallizing in the United States, and although the field's research community remains small, it has been growing all over the world. Every year, universities, funding agencies, and governments increase their support for new centers, conferences, and research networks on both sides of the ocean.

One decisive initiative in the global emergence of the field was the launch, in 2005, of the international Genetically Engineered Machine (iGEM) competition by researchers at the Massachusetts Institute of Technology (MIT) in Cambridge. Every year, teams of undergraduate students and faculty members in all relevant disciplines spend the summer designing and building standard biological components and devices. This year, 85 teams entered iGEM, compared with 13 teams in its first year. Some experts consider the competition the best available introduction to the field. "It will give [you] quite a reasonable test of what [you] can expect in synthetic biology," Krasnogor says.

The last few years, several major centers dedicated to synthetic biology have started up. In 2006, the California Institute for Quantitative Biosciences, for example, launched the Synthetic Biology Engineering Research Center (SynBERC) with a 5-year, $16 million grant from the U.S. National Science Foundation (NSF). Today SynBERC is a major trainer of new synthetic biologists, running dozens of synthetic-biology-related courses at partnering institutions: the University of California, Berkeley , the University of California, San Francisco, MIT, Harvard University, and Prairie View A&M University in Texas. Harvard also recently created the Harvard Institute for Biologically Inspired Engineering with seed support from the university; the center was renamed the Hansjrg Wyss Institute for Biologically Inspired Engineering following a $125 million gift received just a couple of weeks ago.

The European Commission (EC) is currently funding several projects intended "to explore the potential in Europe to develop a very big scientific initiative in this particular field," says Andrés Moya, head of the Spanish Cavanilles Institute for Biodiversity and Evolutionary Biology in Valencia. Among such pan-European initiatives is Emergence, which aims to lay stronger foundations for the field in Europe. EC also supports pan-European research networks, such as SynthCells, which aims to build vesicle-based biochemical reactors. Altogether, in 2007, EC counted 18 synthetic biology initiatives with about €25 million in funding.

Individual European countries are launching initiatives of their own. Earlier this year, the United Kingdom launched its first seven research networks dedicated to synthetic biology. ICL recently launched a new Institute of Systems and Synthetic Biology, which runs a final-year undergraduate course and a Master's of Research degree in synthetic biology. The University of Groningen in the Netherlands launched the Centre for Synthetic Biology, and new courses are in the works at institutions in the United Kingdom, France, and Spain, among other European countries.

But those interested in research--or training--in synthetic biology need not limit themselves to large, top-down initiatives. Synthetic biologists have fingers in so many pots that they can easily repackage their research to fit broader funding calls. EC may fund relevant research proposals and the U.S. Department of Energy, National Institutes of Health, and NSF all accept research and fellowship proposals with a synthetic-biology slant. "Since synthetic biology is an area of interest for NSF, highly ranked proposals in this are more likely to get funded" than similarly ranked proposals in other areas, says NSF program officer Wilfredo Colón. The odds may get even better soon. "Based on published NSF research priorities for FY [fiscal year] '09, funding for synthetic biology may increase in the future."*

Scientists interested in training in the field should join a lab with expertise in synthetic biology. (See our resource page for some top candidates). If you can't find such a lab, join a lab that has expertise complementary to yours and can provide you with the skills you need. "Search for scholarships and research labs and tell people that you are interested in applying either your biological knowledge to the mathematical techniques or the computational mathematical techniques to their biology projects and that you want to give a synthetic biology flavor," Krasnogor advises. 

A Safe Bet

Entering an interdisciplinary field--and staying there--isn't easy, for several reasons. The work is often more challenging, for one thing. Another problem is that you may end up publishing in a wide range of journals covering different fields and your tradition-bound tenure-and-promotion committee may not fully appreciate the value of your work. "It will always be hard for somebody in interdisciplinary research to progress up the career ladder," Krasnogor says.

The goal of building new life forms also invokes a cortège of societal and ethical issues that young scientists must be willing to stand up to. "At some point, these technologies will prove to be a double-edge sword," Glass says. But "if you can be a confident spokesman for the work you do and justify it not as something that is being done capriciously but as something that is being done in order to solve human needs, I think society will be receptive and your work will be rewarded."

Despite these challenges, most experts see synthetic biology as a safe career bet for a talented scientist.

"If you look in the back of Science or the back of Nature, or Google 'synthetic biology jobs,' you'll find lots and lots of them now," Glass says. Indeed, a quick search retrieved a lot of postdoctoral positions, along with a few Ph.D. studentships and tenured or tenure-track faculty positions. 

In some ways, synthetic biologists do "the same things that people have been doing before with a new name and on a bigger scale," Glass continues. "We don't have a written-in-stone definition, Krasnogor adds. "It can take a couple of months to go through the relevant publications and identify a niche where you can contribute." Still, "I think it's a very good opportunity for young researchers." Krasnogor adds.

"Even if synthetic biology would go bust in 10 years, [you would be able to make] a good contribution and branch out," Krasnogor says. By then, a trainee would have gained skills that are "mainstream ... in the pharmaceutical industry, so they could redeploy" quite easily, Kitney says, citing just one of several possible alternative career trajectories.

One of the aims of the field is to develop, if you will, real-life applications. Most experts believe that the future holds many opportunities for synthetic biologists to apply their skills in the private sector. Already, large companies such as DuPont are harnessing synthetic biology, and small companies "are being built around the idea of using organisms, designing organisms, using tools of synthetic biology to make molecules that can't be produced any other way," Glass says.

"If you look at some of the accomplishments from the iGEM competition, you see an extraordinarily rapid evolution of the capacity to use the tools of synthetic biology to build things," Glass says. "The challenges we face trying to solve environmental problems, or create whole new generations of drugs, are enormous, but synthetic biology gives me tools that I never had before. ... It is just a fantastic time to be a scientist."

*Wilfredo Colón is on leave from his position as associate professor in the Department of Chemistry and Chemical Biology at Rensselaer Polytechnic Institute in Troy, New York, where he was profiled by Science Careers in April 2007.

Photos. Top: PhotoDisc. Middle: Brooke Dill, JCVI. Bottom: Courtesy, Andrés Moya

Elisabeth Pain is contributing editor for South and West Europe.