Posts by Laura Sheahan

Podcast on Human Genomics

The 2011 Festival of Ideas themed, The Pursuit of Identity, Landscape, History, and Genetics, is held every other year in Melbourne, Australia to inspire scholars and citizens alike in topics ranging from literature and art to science and foreign policy.  JCVI Professor of Genomic Medicine, Vanessa Hayes participated as a speaker at the festival, and was interviewed for podcast on “Out of Africa: What human genomics is revealing about us.”  The podcast and transcript provide an excellent discussion of modern genomics for a non-technical audience, including a glimpse of the exciting directions in the field and implications for human health.

A video of the session Vanessa Hayes participated in:  The Genetic Revolution I: Health and Human Identity can be downloaded here.

A Look Back at 2010 at the JCVI…

As the J. Craig Venter Institute (JCVI) soars into its 19th year, we reflect on the past year of highlights and accomplishments to mark the close 2010 and look forward to more significant scientific advances in 2011.

JCVI Top 10 of 2010 …

1. First Synthetic Cell: Fifteen years in the making, 2010 brought to bear with huge anticipation the successful construction of the first self-replicating, synthetic bacterial cell. The work was published in Science in May. The synthetic cell called Mycoplasma mycoides JCVI-syn1.0 is the proof of principle that genomes can be designed in the computer, chemically made in the laboratory and transplanted into a recipient cell to produce a new self-replicating cell controlled only by an artificial genome. Although the first synthetic cell was not designed to produce a specific bioproduct, the team has shown that this can be done and the potential benefits are numerous. The research team, lead by JCVI President Craig Venter, Hamilton Smith, Clyde Hutchison, and Daniel Gibson, envision a future where the rapid design and production of biological products using synthetic biology techniques will be used to produce clean fuels, medicines, and other bioproducts. Throughout the course of this work, the JCVI Policy group has extensively engaged in outside review of the ethical and societal implications of this work, including advising the new Presidential Commission on Bioethics on their recommendations for oversight.

M. mycoides JCVI-syn1

M. mycoides JCVI-syn1

2. Synthetic Vaccines: Following on the heels of the announcement of the first synthetic cell, the company Synthetic Genomics Inc. and JCVI announced in October the formation of a new company, Synthetic Genomics Vaccines Inc. (SGVI). The privately held company is focused on developing next generation vaccines that can be rapidly produced and tested, which is especially important for outbreaks of new infectious diseases. SGVI also announced a three-year collaboration with Novartis to apply synthetic genomics technologies to accelerate the production of the influenza (flu) seed strains required for vaccine manufacturing. The seed strain is the starter culture of a virus, and is the base from which larger quantities of the vaccine virus can be grown. Under this collaboration, Novartis and SGVI will work to develop a “bank” of synthetically constructed seed viruses ready to go into production as soon as WHO makes recommendations on the flu strains. The technology could reduce vaccine production time by up to two months, which is particularly critical in the event of a pandemic.

3. Hydra Genome – one of the animal kingdom’s earliest common ancestors: JCVI scientists along with more than 70 other researchers from around the world, have sequenced and analyzed the genome of Hydra magnipapillata, a fresh water member of the cnidaria– stinging animals that include jellyfish, sea anemones and corals. The research, published in the March 14 edition of Nature, was co-led by Ewen F. Kirkness, JCVI, Jarrod A. Chapman, Department of Energy Joint Genome Institute, and Oleg Simakov, University of California, Berkeley. This is the second sequenced cnidarian genome, following that of a sea anemone, Nematostella vectensis, in 2007. The ancestors of these two species diverged more than 500 million years ago, and comparison of their genomes has revealed common features of the earliest animals that gave rise to the diversity of animals on Earth today. The team found clear evidence for conserved genome structure between the Hydra and other animals, like humans. Unexpectedly, the sequencing also revealed a novel bacterium that lives in close association with the Hydra.

4. Uncovering the Human Microbiome: Microbes are living within and on the human body and this collective community is called the human microbiome. JCVI Scientists, as one component of the large scale NIH Roadmap Human Microbiome Project, and along with colleagues at three other genome centers sequenced the genomes of ~180 microbes from the human body, published in the May 21 edition of Science. At the JCVI we anticipate sequencing an additional 400 species over the next few months. Colleagues at the JCVI are also using single cell approaches to isolate new strains that have not been cultured – isolates whose genomes will also be completely sequenced. The role these microbes play in human health and disease is still relatively unknown and these approaches are allowing us to gain a greater understanding of these enigmatic species.

5. Body Louse Genome: A global research team led by Ewen Kirkness and colleagues from JCVI published a study in the Proceedings of the National Academy of Sciences in June describing the sequencing and analysis of the human body louse, Pediculus humanus humanus, a human parasite responsible for the transmission of bacteria that cause epidemic typhus, relapsing fever and trench fever. Detailed analysis of the genome was then conducted by a large international group of 71 scientists, coordinated by Barry Pittendrigh, University of Illinois, and Professor Evgeny Zdobnov, University of Geneva Medical School. Comparative studies of the body louse genome with other species revealed features that will enhance our understanding of the relationships between disease-vector insects, the pathogens they transmit, and the human hosts. In addition to the targeted louse genome, the project unexpectedly yielded the complete genome sequence of a bacterial species, Riesia, that lives in close association with lice, and which is essential for survival of the insects. The researchers believe that the genome will be a valuable reference for evolutionary studies of insect species, especially in the areas related to insect growth and development.

6. Castor Bean Genome Sequencing: A research team co-led by Agnes P. Chan and colleagues from JCVI and Jonathan Crabtree and others at the Institute for Genome Sciences, University of Maryland School of Medicine, published the sequence and analysis of the castor bean (Ricinus communis) genome in Nature Biotechnology in August. Because of the potential use of castor bean as a biofuel and its production of the potent toxin ricin, the team focused efforts on analysis of genes related to oil and ricin production. The analyses could be important for comparative studies with other oilseed crops, and could also allow for genetic engineering of castor bean to produce oil without ricin. Identifying and understanding the ricin–producing gene family in castor bean will be important in preventing and dealing with potential bioterrorism events. Genomics enables enhanced diagnostic and forensic methods for the detection of ricin and precise identification of strains and geographical origins. As a next step, the group suggests further comparative genomic studies with the close relative cassava, a major crop in the developing world, to further elucidate their disease resistance aspects.

7. Science Education: JCVI was an Official Partner of the inaugural USA Science and Engineering Festival held on the National Mall in Washington, DC in October. The Festival, which was the country’s first national science festival, included over 500 of the country’s leading science and engineering organizations with the aim to reignite the interest of our nation’s youth in the sciences. The JCVI ‘Discover Genomes’ Bus was showcased during a two-day expo and some of the research being done at JCVI was presented to around 1700 visitors by our scientists and staff.

There were lines all day!

8. Viral Genomics– In 2010 the JCVI has published over 1600 influenza genomes and over 75% of all published flu genomes to date have been sequenced by the JCVI, totaling over 6000 genomes. This year the diversity of viral genomes we have sequenced has significantly expanded under the NIH Genomic Sequencing Center for Infectious Diseases contract. Some of the projects include viruses causing diseases such as measles, mumps, rubella, encephalitis, SARS, and the common cold, just to name a few. The viral group has annotated and published 79 Rotavirus (stomach flu) and 33 Coronavirus genomes (includes SARS and common cold) this year and many more will be published in 2011. The pace of sequencing and finishing genomes has also increased this year as a result of adoption of nextgen platforms (e.g. Illumina/454 and Illumina/Solexa) and the development of more efficient methodologies to increase productivity while reducing costs.

9. Marine Microbial Genome Sequencing Project: JCVI scientists have continued their quest to isolate and sequencing microbes living in global ocean waters to discover new genes and enzymes, and to help understand the role microbes play in the ocean ecosystem. Shibu Yooseph, Kenneth Nealson and colleagues at JCVI published an analysis of 137 known marine microbial genomes living in the global ocean surface in Nature in November. These genomes were compared to metagenomic samples of ocean waters of 10.97 million sequences of JCVI’s Sorcerer II Global Ocean Sampling (GOS) metagenomic data and thousands of 16S rRNA sequences. The marine genomes were collected as part of the Gordon and Betty Moore Foundation-funded Marine Microbial Genome Sequencing Project, a project coordinated by JCVI that has a primary goal of obtaining whole genome sequences of ecologically important microbes from a variety of diverse, global marine environments. The work provides a good example of combining metagenomic data with sequenced genomes data to study microbial communities and to generate testable hypotheses in microbial ecology.

10. Sorcerer II Global Ocean Sampling Expedition: On December 17th 2010 Sorcerer II arrived in Florida after spending the last two years with her crew collecting samples in The Baltic, Mediterranean and Black Seas. Funded generously by the Beyster Family Foundation Fund, The San Diego Foundation, and Life Technologies Foundation, Sorcerer II has sailed ~28,000 nautical miles since departing San Diego in March 2009. During this time 212 samples were collected and over 5,100 liters of sea water was filtered and sent to JCVI for analysis of the microbial life contained within these samples. The JCVI established strong collaborations with scientists in all 16 countries in which samples were collected, which will lead to joint publications and future collaborative studies in the new year. Read more.

Sunrise in the Ligurian Sea

Looking Forward to 2011…

Ten-year anniversary of the Human Genome Project: To commemorate the anniversary of the publications of the first human genome sequences in 2001, JCVI and Nature are hosting a conference and celebration in February 2011 titled – Human Genomics: The Next 10 Years. The conference will look forward to the promises of human genomics for the next 10 years, with sessions on medical advances related to genomics; the technological and ethical challenges of human genomics; personalized and familial genomics; the human microbiome project; variation in the human genome; and making sense of the genetic code. This conference will be a great way to jump into the new year and inspire the grandiose ideas and achievements that genomic scientists will accomplish over the years to come.

Scientist Spotlight: Meet Vanessa Hayes

Geneticist Vanessa Hayes does not think small nor move slowly—from completing her post doc in six months (the US National average is 3 to 7 years) to completing the first South African Genome Project in 2010 with her goal set on defining the extent of human diversity in all populations, she is on a mission.  Just 11 years outside her post doc she has the credentials of someone who has been in science much longer. Her work and talent has taken her to remote regions of Southern Africa, all over Australia, Europe, the U.S. and now to the J. Craig Venter Institute with her appointment as Professor of Genomic Medicine at the San Diego facility.

Of Cartoons and Men…

Born and raised in South Africa, Vanessa first headed a laboratory near Cape Town to investigate genetic susceptibility to HIV/AIDS after earning a Ph.D. in 1999 in Medical Genetics at the University of Groningen, Netherlands. After three years at the University of Stellenbosch she moved to Sydney, Australia to become group leader of Cancer Genetics first at the Garvan Institute of Medical Research, and later at the Children’s Cancer Institute of Australia. During those years she began two major cancer research projects that continue today. One is a study to assess how ethnicity impacts prostate cancer risk and outcomes by genetic profiling men with and without prostate cancer from different ethnic and geographical locations (initially South Africa and Australia). “I believe in going to the extremes of phenotypic diversity to understand genotype – for example the clinical disparities of prostate cancer in Africa compared to non-African populations has not been adequately explored,” she said explaining that the genetics of ethnic diversity is one of her main research interests. “We don’t always have clear clinical definitions to describe phenotype, but genomics can help to define disease,” she added.

This cancer research then led her to what might seem like an unlikely suspect–the Tasmanian devil. The inspiration for a much beloved Looney Toons character and the largest carnivorous marsupial indigenous to Australia, Vanessa became acquainted with the devil when learning that it was a good model for human cancers. She partnered with Stephan Schuster of Pennsylvania State University to sequence the animal using next-generation (gen) sequencing, in turn establishing the then first next-gen sequencing research laboratory in Australia.  By establishing a Tasmanian devil genome, she and her team were able to define the extent of dwindling genetic diversity within the devil population as a result of an unusual infectious facial cancer. The hope is that this information and tools developed will be used for the insurance breeding program, which has been established by Australian authorities to save this iconic species from inevitable extinction within the next decade.

Putting Africa on the Genetic Map

In early 2010 Vanessa embarked on another collaborative effort with Schuster’s lab, this one to help get African populations represented in genetic databases and reap the benefits of human genomics research. The initiation of the South African Genome Project was a key step in helping to define the extent of human variation, the relevance to assessing disease risk, and the response to various medicines. The effort was conceived out of Vanessa’s frustration in earlier studies with African populations when she found a complete lack of African reference genomes and susceptibility gene array profiles in existing databases. Africa, believed to be the birthplace of mankind with the oldest populations, offers a much greater diversity than found in individuals of European decent. Another issue with the existing databases was that the little African genetic data represented in early 2010 was based on one population – the Yoruba people from Nigeria. Demonstrating that the Yoruba people are clearly not representative of the majority of the over 500 different linguistic groups in central to southern Africa, Vanessa was determined to change the face of European-driven genomic research.

Vanessa and a Bushman lady from the Southern African Kalahari desert in deep discussions about what we can read in the blood (aka genomics). This lady is one of only a few click-speaking hunter-gatherer peoples left who represent an ancient line for all modern humans.

Vanessa and a Bushman lady from the Southern African Kalahari desert in deep discussions about what we can read in the blood (aka genomics). This lady is one of only a few click-speaking hunter-gatherer peoples left who represent an ancient line for all modern humans. (photo credit: Chris Bennett - www.chrisbennettphoto.com)

Ingenuity and perseverance led Vanessa to knock on the door of Nobel Peace Prize recipient Archbishop Desmond Tutu. He was, she knew, a critical step needed to gain access to a potential treasure trove of South African genetic data. She made her case directly to the Archbishop in front of a room of advisors who told him not to participate in a genetic study. However, much to her surprise, Tutu agreed to be the first South African to have his genome sequenced. Vanessa believes he did so, against the advice of his advisors, because he knew the importance of this type of research to the people of his country. The Archbishop’s participation was both critical and significant as he represents not only the Bantu linguistic group to which 80% of the South African population belongs, but he is also a survivor of TB, polio, and prostate cancer. The researchers were able to correlate his genetic markers (genotype) potentially associated with disease susceptibility with his family and medical history (phenotype), providing valuable information about the Bantu people. Vanessa and her team also sequenced the complete genome and three exomes (protein-coding genes only) from four individuals representing diverse ethnic groups of what are known as the Kalahari Bushmen. Bushmen (or San) is the term for the click-speaking hunter-gatherers who inhabit the Kalahari Desert, which spans parts of Botswana, Namibia, and Angola. Her studies, published in Nature in 2010, showed that two different linguistic groups of Kalahari Bushman were as genetically divergent as Europeans and Asians. Some found this finding surprising, however, the extent of the diversity should not be surprising considering these Bushman represent the oldest living lineage of modern humans.

By this time in 2010 Vanessa decided she had reached the technological limits of her research in human genomics in her current position in Australia. She was searching for a place to expand her capabilities, particularly in next generation (gen) sequencing and bioinformatics. She was interviewing last spring in Melbourne at the Walter and Eliza Hall Institute for Medical Research where Dr. Craig Venter happened to be giving a keynote lecture. The JCVI was not on her radar at the time as she had several job offers within and outside Australia, but Craig was able to convince her to come to work with him and the team at JCVI.

Sleep is overrated

The sequencing of Archbishop Tutu was only a start to Vanessa’s plans in human genomics research. She is continuing to expand her work with indigenous groups in Africa. Much like the aspirations (and accomplishments) of her new boss, she claims a ‘modest’ goal: “To define the extent of human diversity that exists globally so we can have a true picture of variation that human genomes have and to help make sense of that variation by linking genotype to phenotype.” Phenotype cannot only mean disease conditions (associated with genes) but also evolved behaviors. For example, how the Bushmen are able to go for a week without water in the desert climate is a phenotype that may be encoded in their genes. Understanding the genetic basis for disease and behavior in different populations will certainly be a challenge, but clearly Vanessa is a person who thrives when presented with challenges.

Vanessa’s limited spare time revolves around her family, including two children — each born on different continents — who keep her busy with the latest goal to teach mom how to surf! A keen soccer player in Australia, she has turned to a new adventure since her move to San Diego, kickboxing.  She says she doesn’t get much sleep, particularly little in the past three years, but at least now she’s working mostly on U.S. time rather than two opposite time zones.

If she had time for another career, “it is hard to think of another career as I am doing exactly what I love, combining my passion for the rich-diversity of people from Southern Africa (and globally) from whom we have so much to learn, with the speed and dynamics of everyday life of 21st century science. What better place to combine these two worlds than here at JCVI.” Vanessa hopes via her new position to understand and educate others about the breadth of human genetic diversity existing in populations worldwide.

Influences of trace metals on biological evolution

Scientists show how trace metal chemistry and global changes in oxygen have influenced the evolution of metalloproteins and the Eukaryotes

June 4, 2010 – A paper is being published in PNAS this week about how the varying abundance of trace metals in the environment has influenced biological evolution. The research team, led by Chris Dupont of the J. Craig Venter Institute and Gustavo Caetano-Anollés at the University of Illinois, correlated environmental changes in metal availability over the past 3 billion years ago with the critical events in the evolution of the three superkingdoms of life (Archaea, Bacteria, and Eukaryota).

Billions of years ago, ocean chemistry was dramatically different from today. Completely devoid of oxygen, trace elements such as iron, manganese, and cobalt were abundant. The evolution of photosynthesis resulted in an increase in atmospheric oxygen around 2.4 billion years ago and prompted a series of chemical changes. Over the next 2 billions years the ocean slowly started to accumulate oxygen, increasing the amount of zinc, copper, and molybdenum that was available. At the same time, iron became very rare.

Nearly all biological pathways require metalloproteins (enzymes that bind metals) that are critical for cellular function. The metals utilized by biological life include: Mg, K, Ca, Fe, Mn, Zn, Cu, Mo, Ni, Se, and Co, yet the utilization of these elements varies between organisms. Of these, Fe, Zn, and Ca are the most utilized. Early life, the authors said, lacked both the structures required to control intracellular metal concentrations and the metal-binding proteins themselves involved in electron transport and redox reactions. Within the timeline of protein structure evolution, the invention of proteins that transport and sense metals coincided with the birth of electron transport, as well as the first unique cells. Essentially, the ability to control intracellular metal concentrations appears to be one of the fundamental definitions of biological life.

The first organisms predominantly used metals that were abundant in the ancient ocean, Fe, Mn, and Co. This bias in utilization is preserved to this day in the Bacteria and Archaea, who still predominantly use ancient protein structures. Later, as the ocean accumulated oxygen, new proteins evolved that bound zinc and copper. So did the Eukaryotic superkingdom, which includes all organisms with a nucleus, from single-cell plankton to humans. The authors found that the new zinc and copper-binding proteins are only found in Eukaryotes, not in the Bacteria and Archaea. The nucleus houses most of the new zinc binding proteins and this unique utilization of zinc is one of the defining features of all Eukaryotes. One speculation advanced by the authors is that zinc concentrations in the ancient ocean were too low to allow for the evolution of the Eukaryotes, at least until global changes in oxygen occurred.

This work was funded by the NASA Astrobiology Institute and Dr. Dupont is a collaborator at the “Follow the Elements” NAI institute at Arizona State University. Co-authors on the study include Andrew Butcher from the University of York (UK) and Ruben Valas and Dr. Phil Bourne at the University of California, San Diego.

Scientist Spotlight: Hamilton O. Smith and Clyde A. Hutchison III

Two of the superstars of science at the helm of the effort to make a synthetic cell (a cell with a completely man-made set of genetic instructions) are Hamilton Smith and Clyde Hutchison, or Ham and Clyde as they are affectionately known to colleagues. Since 2003 when they started working together here at JCVI one rarely hears about one without the other – always together and cracking jokes amidst discussing the complexities that define their ultimate quest: To understand, “What is Life?” I like to think of them as the Abbott and Costello or Laurel and Hardy of science. A colleague said they reminded him of Statler and Waldorf – the muppet men on the balcony heckling the other characters –although Ham and Clyde are neither ornery nor disagreeable but their subtle banter with each other is hilarious. They play off each other perfectly and I had the pleasure of interviewing them for a more personal piece to coincide with the landmark announcement of their trailblazing work to make first living synthetic cell.

Hamilton Smith and Clyde Hutchison III

Hamilton Smith and Clyde Hutchison III

So I was to begin the interview diligently with a list of well thought out and leading questions that fed nicely into the next. Those quickly went out the window when Ham and Clyde walked into the room (them in San Diego and me in Rockville over a videoconference). “I cleaned the stain off my cuff!” declared Clyde holding up his sleeve, and “we wore our good suit jackets,” thinking I would be interviewing them in person. “Will this be recorded by video?” “No, no audio or video” I replied, “so you can say anything you’d like to and I’ll capture what I can with my pen.” They started talking before I could pose a question and I settled back for a hugely enlightening hour of landmark scientific achievements and hilarious stories. The Early Years Ham grew up primarily in New York and Illinois with a family who valued education and encouraged his interests in science and medicine. His father was a professor of education and his mother an aspiring writer. Ham was a mathematics major at the University of Illinois with an interest in neurophysiology, and attended medical school at Johns Hopkins University where he later would spend the majority of his career doing research. In 1978 he won the Nobel Prize in Physiology or Medicine for his work on restriction endonucleases (enzymes made by bacteria that cut DNA in specific places; the isolation of these enzymes provided a vital tool for molecular biology research). When asked how the Nobel had affected him Ham said modestly, “Getting the Nobel was a nice thing. I became nervous about how I should behave. I always looked up to Nobel Laureates but didn’t’ feel like I was one of them.” One of the perks he said was that he could “apply for any grant and get it!” Ham lamented that “Clyde should have gotten the prize in 1993 with Michael Smith” for their work on site directed mutagenesis. But Clyde is not the kinda guy who promotes himself like you need to for things like this,” said Ham. Clyde hastily added, almost interrupting him, “Ham isn’t the type either but he had good promoters.” But apparently his parents weren’t one of them! Clyde relayed a story about how Ham’s parents found out about the prize when they were listening to a radio show and heard the announcement that Hamilton Smith from Johns Hopkins received the Nobel Prize. His mother turned to his father and said, “I didn’t know there were two Hamilton Smiths at Johns Hopkins!” Ham slightly corrected Clyde’s story and said it was more like, Do you suppose there is another Hamilton Smith at JHU?” Modesty and humility are in his genes. Clyde also had a very supportive family who nurtured his interest in science at a young age. His father was a chemist and physicist. “A chemical physicist” said Clyde, “rather than a physical chemist.” Being a physical scientist his father looked down on biology as “messy business.” Although Clyde was a physics undergrad at Yale he eventually ended up in biology and joked that, “It allowed me to do science but rebel against my father.” Most kids rebel by getting tattoos or ditching school, but apparently Clyde wasn’t like most kids. Clyde’s entry into biology was serendipitous. He was on a scholarship at Yale and in order to maintain it he had to have a part time job. The first year everyone was put in the dining hall, but the 2nd year he lined up a job with an astrophysicist involved in radiotelescopes. By the time Clyde returned to school from summer break the professor gave the job to someone else. Clyde pleaded with school administrators for a science job and got into the Biophysics department working with then postdoc Carl Woese who discovered the 3rd branch of life- Archaea- and that piqued Clyde’s interest in biology. Clyde later moved to North Carolina and spent over 37 years at the University of North Carolina, Chapel Hill building an illustrious research career. How They Met In 1973 Ham and Clyde were both independently invited to a conference on restriction enzymes in Belgium and stayed in a monastery. “We don’t really remember meeting each other,” said Ham but he distinctively remembers the communal bathroom (back then a novelty). It wasn’t until 20 years later that the two made a real connection. Craig Venter and Ham met in Bilbao, Spain in 1993 at a meeting. Craig gave a presentation on his Expressed Sequence Tag (EST) work at NIH. Ham said they met in the hotel bar and from that time on they liked each other as their science interests were similar. Craig soon afterward asked Ham to be on the Scientific Advisory Council for TIGR (The Institute for Genomic Research). “I saw the sequencing lab and that instantly convinced me” said Ham. “The biggest I’d ever seen! I was impressed by [the technology] he had.” Around 1994 Ham called Clyde to collaborate on a sequencing project. Craig, Ham and the team at TIGR had just sequenced the first bacterial genome, Haemophilus Influenzae. Ham noticed Clyde’s work on Mycoplasma genitalium and since it’s the smallest known bacterial genome he thought it would be a good candidate for their next sequencing project. That simple project would eventually turn into the quest to create a synthetic cell. Ham said that “synthetic genomes were discussed” by he, Clyde, and Craig starting around 1996. Then, with a wink, Ham said that he “made an offer Clyde couldn’t refuse” and they collaborated to sequence M. genitalium. Clyde split his time between TIGR and UNC, while Ham and Craig slowly wooed him into joining full time in 2003. After sequencing the M. genitalium genome (published in 1995), they began work on the “minimal genome project.” The goal of this project was to see how many genes are necessary to sustain life, and in this case they studied the genes essential for the growth of M. genitalium because it is a bacterium with the smallest genome known. This work was published in the journal Science in 1999. At the same time a group of bioethicists from the University of Pennsylvania published the results of their ethical review of this work. By July 1998 Ham retired from JHU to work full time at TIGR. He was there only a month before leaving for Celera, the biotech company Craig founded to sequence the first human genome. Ham and Craig were at Celera from 1998-2002 and had the idea to do the synthetic cell from Clyde’s work then but put it on hold for four years until after the draft human genome was finished. Early in 2002 Craig left Celera and founded two new institutes: the Institute for Biological Energy Alternatives (IBEA), and The Center for the Advancement of Genomics. Ham resigned from Celera to join IBEA (where he became scientific director) and “cashed in my stock” he laughed only half-joking. Ham and Clyde finally started working closely in 2003 when Clyde moved full time to work at IBEA, and since then have been inseparable. Clyde and Ham both did phage work in graduate school. Clyde worked primarily on phiX174, a phage virus that infects E. Coli. They thought this would be a good first target to test their new synthetic biology technology. They received a Department of Energy (DOE) grant to synthesize phiX in the lab and worked on it during the summer 2003. “Both of us moved into the Marriot Residents Inn and worked 12 hours a day on the synthesis of phiX” said Ham. He proudly added that Craig said, “We were the best postdocs he ever had!” Considering Ham was in his early seventies then and Clyde was not far behind, that was a pretty impressive claim! The synthesis of phiX was published in 2003 and laid the ground work for synthesis of a larger genome — that of a mycoplasma bacterial species. One of the keys to working together so well is how they complement each other both personally and professionally. When asked about how they would characterize the other, Ham divulged the important attributes first, “Clyde likes martinis and I like manhattans!“ he blurted out smiling. Ham continued, “I like his sense of humor very much. He’s very precise in his speech and thinking, whereas I get a little more disorderly. But our approach to science is very similar.” Clyde added that “Ham is great at coming up with things that should have been obvious to everyone but aren’t.” Key to Success I wanted to know what makes these two extraordinary men tick. What motivates and inspires their drive and successes — Good mentors? Good luck? Sacrifices? Hard work and determination? Or just a good time to be in biology? Clyde said simply, “You have to want to do good things, and have a motivation to do interesting science. We both have an aptitude for it, but need to just do things and see what happens.” So they appear to be open to risks and new adventures in their careers, maybe they could even be described as mavericks as Craig has been called. Ham said, “If I hadn’t met Craig I’d be retired and living on the farm (his wife of 53 years maintains the farm in rural Maryland). “Craig has given me the opportunity to continue [doing science]. Clyde added that “being at the JCVI (J. Craig Venter Institute) has made it possible to do things we couldn’t do otherwise in an academic setting.” For example, Ham said, “When sequencing first took off in the late 80s a lot of good scientists didn’t see value [with pure data collection]. I’ve always said “sequence, sequence, sequence” then later we can figure out what to do. “It’s the code of life!” Ham performed his first sequencing experiment in 1976 using the Maxim-Gilbert method and realized its potential back then. “But I was sequencing before Ham,” said Clyde who trumped him in that area by doing a sabbatical in Fred Sanger’s lab in 1975. Speaking of aptitude, science isn’t the only activity at which Ham and Clyde excel. Ham played classical piano starting age 7 or 8. He never practiced and said he was a lousy pupil. Every 6 months or so his mother said he could quit. At age 12 a friend took him to a music store where he heard the Pathetique Sonata by Rubenstein that he had struggled to play and when he heard it for the first time he felt an instant change – he started practicing 3-4 hours a day up to 8 hours a day during the summer. It’s not a surprise that this type of diligence contributed to his later successes in life. Presumably complimenting Ham’s ability to tickle the ivories, Clyde said, “He’s remarkably fast with his hands and can shuck edamame faster than anyone.” Ham added that “I was the fastest newspaper shuffler and hand-bill stuffer in high school.” He would race his friends to finish the chores. Clyde also took classical piano lessons as a kid but quit after a few years to take up the saxaphone and clarinet. He listened to jazz alot and learned how to play in his forties, going on to perform regularly in clubs in North Carolina. Although he stopped taking formal piano lessons as a youth he has kept up with it to this day. He is now playing solo piano accompanied by computerized bass and drum every Thursday in a restaurant in La Jolla called Bernini’s Bistro. What is Life? To finish up the interview I wanted them to leave us parting words of wisdom and so asked, “When you look back on your illustrious careers do you think about how far science has come or how far we have to go to understanding “What is life?” Ham: “It’s hard for me to believe how far we’ve come. If you think about how far things have come since sequencing the first mycoplasma genome (15 years ago) it’s hard to conceptualize what it will be like in 15 years.” Clyde: ”We grew up reading Dick Tracy with his wrist radio, and the iPhone makes the wrist radio look like trash.” When I asked what he meant by a wrist radio, he explained that the comic book character, Dick Tracy, used it to communicate. Ham added that if you sent in cereal box tops they would send you a wrist radio. “It didn’t work of course but you pretend,” he smiled. Ham and Clyde then started to banter about the fantasy uses of wrist watch radios. I threw out an analogy I was familiar with – the legendary 80s show, “Knight Rider” and the “Kit” car that David Hasselholf could summon on his wrist watch. They nodded in familiarity and added that some cars today can parallel park themselves. Getting back to the question of “What is life” I asked them if synthetic biology will provide more for us initially as a research tool in molecular biology or as a chassis for production of bioproducts. “Both” they chimed together. Clyde remarked, “It will have a lot of basic science value that will allow us to get at questions that motivated us in the beginning such as, what are the minimal number of genes essential for life?” “It will promote a better understanding of cells” added Ham. There will be practical applications too, Clyde continued, but “this synthetic cell [M. mycoides ] is not a good production host to make useful bioproducts since it’s expensive to grow and fastidious (requires special nutrients).” “But it provides the proof of principle that it can be done,” Ham exclaimed. We’ve developed a bunch of methods that we can build whatever chromosome we want as long as we know the DNA sequence, said Clyde. Using synthetic genomics “we can take apart a cell and figure out what every gene does in that cell. There is currently no cell we can fully understand,” said Ham. We can reduce the number of genes we don’t know down to a dozen or so and once we’ve done this “then I retire” Ham grinned. I ended the interview asking which comedian duo they thought they most resembled- Abbott and Costello or Laurel and Hardy. They both kind of shook their head not thinking that was a good analogy. But that same moment (just before the videoconference equipment unexpectedly cut off our connection), Clyde said with a laugh, “Neither, but maybe the Keystone Cops!” There they ended the interview as they began – being unduly modest, charmingly funny and easy. And to think these two individuals have been key figures in science, whose work has spanned both the dawn of molecular biology continuing through to the dawn of a new frontier in science- writing the code of life.

Scientist Spotlight: Orianna Bretschger

Most of us have never thought about how to make more water or cleaner water or develop unique sources of energy but that’s exactly what Orianna Bretschger does at JCVI.  She is working at the intersection of engineering, physics, and biology to design small machines powered by bacteria that can purify wastewater and generate electricity at the same time.

Orianna Bretschger

Orianna Bretschger

Working in alternative energy was a natural career choice for Orianna since she grew up in the desert in Arizona where water was a precious and finite commodity. She also lived in places without electricity or plumbing.  One place, that holds fond memories for her, had an old-fashioned windmill that was used to pump water into an open tank for cattle.

Orianna always had an interest in science, especially astronomy, and with that interest, coupled to good teachers who always inspired her, she found her way to where she is now.

At an early age, Orianna entered the Young Astronauts program.  She had been introduced to the program by the school director, who happened to be a nun, who was at one time on the short list for the “teacher in space program.”  By junior high Orianna had attended two International Young Astronauts conferences, toured the Johnson and Kennedy Space Centers, and travelled to the former USSR with her mentors and another student to help build relationships with Young Kosmonauts; a trip that solidified her love of science.

In high school she expanded her science interests to physics and planetary science, and had the opportunity to present a poster at a Lunar and Planetary Science conference at the Johnson Space Center in Houston.  Incidentally, her teacher for these courses was also her cross-country coach – he encouraged her to go to school at Northern Arizona University, in Flagstaff, AZ (where the “dwarf planet” Pluto was discovered) where she earned a merged degree in physics and astronomy.

After her undergraduate education, Orianna went into industry, landing a job at Raytheon Missile Systems in Tucson, Arizona. There she worked on guidance systems, supporting projects in the Electro-optical subsystems department for two years, something she considers to be a great experience.  As part of her work there on the Algorithm and Analysis team she developed algorithms for the guidance systems and began the efforts to test and validate the system. As part of her job she got to fly in old military planes, collecting and analyzing flight data and system performance.

At the end of two years at Raytheon, she still had not made the decision to attend graduate school but instead headed to Authenti-Corp, a company that is involved in biometrics evaluation (e.g. facial and voice recognition devices, fingerprint and iris scanners, digital signature verification, smart cards etc.)  where her primary job was working with the Department of the Army Biometrics Task Force to develop policies and procedures for biometric systems testing and implementation. She decided that government contracting was not for her, and subsequently worked various jobs for a couple of years, including bartending in her time off, to prepare for grad school.

Orianna decided on University of Southern California, where she was accepted into the Materials Science Ph.D. program in the School of Engineering. She spent her first semester working in a Carbon Composites lab, and later met Ken Nealson in the Biology Department where she began working on microbial fuel cells (MFCs) in Ken’s laboratory.   Graduate work was focused on identifying the specific genes in the organism Shewanella oneidensis MR-1 involved with electrical current production, and solid-phase manganese and iron oxide reduction. She also led the effort to characterize the power performance, fuel flexibility, and metabolic activity of several other Shewanella wild-type strains and environmental enrichments. Throughout these projects she was given the opportunity to learn and practice microbial physiology, reactor design, electrochemistry, analytical chemistry, and environmental engineering.  She graduated in the summer of 2008 and then joined JCVI with Ken.

Orianna really enjoys the diversity of science at JCVI and according to her the wonderful people make for a terrific work environment. Specifically her interests are to extend the technology for sustainable wastewater treatment, energy recovery, and develop MFC systems for the study of microbial physiology.  Ten years from now she hopes to be tenured faculty, and believes her work with engineered and biological systems will ultimately contribute to developing healthy and sustainable water management practices throughout the Southwest and worldwide.

Note: Adapted from the original article written by Karen Nelson, Director of JCVI’s Rockville campus.

Scientist Spotlight: Karen Nelson

Karen’s interest in the natural world was sparked at a young age. Born in Jamaica, she enjoyed the outdoors and wonders of nature. Karen was drawn to animals and wanted to become a veterinarian, but after taking some human and animal nutrition courses in college she was hooked on microbiology. Karen received her B.Sc. in Animal Science from the University of the West Indies, Trinidad and Tobago, her M.Sc. in Animal Science from the University of Florida, Gainesville, and her Ph.D. in Microbiology from Cornell University. The confluence of her interests led her specifically to the study of ruminant microbiology at Cornell. Here she learned that the microbiome, the native microbial populations within an animal, could be very important to its health and well-being. Besides learning all she could about the fistulated and canulated animals, her fondest memory of graduate school is the night when 4 feet of snow was dumped onto campus. It must have been quite the sight for this native Jamaican!

Dr. Karen Nelson

Dr. Karen Nelson

Karen joined JCVI’s legacy organization, The Institute for Genomic Research (TIGR) as a postdoctoral fellow in 1996 where she was drawn to the possibility of elucidating the genomes of archaea, which were at the time, a relatively new domain that had extremely interesting species that are adapted to extremes of pH, temperature, and pressure and that also play a crucial role in the rumen to maintain hydrogen potential. Since then she has steadily risen to become one of the leaders in the fields of microbial and metagenomics research. She considers herself a microbial physiologist who uses genetic tools to link general biochemistry and environmental microbiology, in a sense adding real world context to the vast genomic datasets. When asked what it is about microbes that fascinates her, she said, “It’s the fact that these ‘simple’ organisms are far more complex than we ever thought.” Her early work at TIGR in sequencing Thermotoga maritima, a bacterium isolated from a thermal vent off the coast of Italy solidified this belief. Here was an organism from domain Archaea whose genome revealed that many gene sequences resembled those of Bacteria, suggesting that this organism either shares a deeply rooted ancestor or that it had exchanged segments of it genome across domains through lateral gene transfer –providing critical insights into microbial evolution.

At JCVI she is working on projects including the Human Microbiome Project (HMP), which is a major initiative sponsored by the National Institutes of Health to sequence the plethora of organisms living on and within our bodies. The goal of this project is to sequence and understand these microbes and their contributions to human health and disease. The challenges of this project are many, not the least of which are the shear numbers of organisms living within a healthy human. Karen and her group were part of a national team of researchers who completed the first comprehensive microbial survey of the human gastrointestinal tract. In addition to the human microbiome work she and her team conduct, they are also collaborating with the University of Illinois to investigate the microbial diversity of 24 non-human primates including bonobos, our closest primate relatives. She also continues to be involved in a variety of other metagenomics projects, including studies of the rumen and corals

In December 2009, Karen was promoted to the position of Director of JCVI Rockville, MD Campus, where she will help to grow the research programs and continue her trail-blazing studies in fields of microbial physiology and metagenomics.

Note: Adapted from the original article written by Greg Wanger of the JCVI Microbial and Environmental Genomics research group.

Kudos to Ken!

JCVI Professor, Kenneth Nealson, has been selected by the American Society of Microbiology to receive an award that recognizes distinguished accomplishments in interdisciplinary research and training in microbiology.  The 2010 David C. White Research and Mentoring Award will be awarded to Ken for his trail blazing work that began in the 1970s to bridge the geological and microbiological sciences.   At the JCVI he is leading the Microbial and Environmental Genomics group and established the JCVI Electromicrobiology team doing exciting research on microbial fuel cells with applications ranging from water purification to bioenergy.  Read more about Ken’s accomplishments

Scientist Spotlight: Greg Wanger

Greg Wanger

Greg Wanger

Greg Wanger was 3.7 km below the Earth’s surface, trapped not only underground but also in a country distant from his native lands of Canada and Liechtenstein. He looked around him. It was very hot and smelled like rotten eggs. As many people do during their graduate careers, Greg pondered the questions: “What was I thinking when I agreed to this project? Does my advisor know what he’s doing? Am I claustrophobic, or just paranoid about being claustrophobic?”

JCVI’s own science version of Indiana Jones, Greg Wanger, joined JCVI as a postdoctoral fellow in the Electromicrobiology Group in the San Diego laboratory in March 2008. His graduate work mirrored projects at JCVI, among them Global Ocean Sampling expedition. He traveled to remote environments (replace Sargasso Sea with South African gold and platinum mines) in search of unknown genes (replace metagenomic ocean sampling with metagenomic deep mine sampling). Greg spent a little more than three months in South Africa as part of a team sampling for unique life. They expected to do metagenomics on a mixed population, but as is often the case in science, turned up something completely different–a single-species ecosystem. Their organism, Candidatus Desulforudis audaxviator, has been billed as a possible model for alien life, since it lives in very harsh conditions alone without light or oxygen.

Greg’s decision to go into science was formed at the tender age of four when on vacation at the family cottage his uncle’s father, a biology professor, came to visit. The professor had a series of “experiments” laid out for Greg, such as catching and dissecting a fish. At the end of the weekend the professor made Greg promise that he would remain a scientist from that point forward. True to his word, Greg pursued his life-long interests in science. While in college at the University of Western Ontario Greg was one of only two students enrolled in a class on Geomicrobiology. This class was taught by the professor who would turn out to be Greg’s future graduate advisor and really sparked his interest in microbiology. After completing his undergraduate work, he entered graduate school excited about pursing work in this burgeoning new field within the Earth Sciences department.

Wanger continued making fortuitous connections leading to next steps in his scientific career. During his last year of graduate school he attended a conference where he met Yuri Gorby, a pioneer in electromicrobiology research, who offered Wanger a postdoctoral position at the J. Craig Venter Institute (JCVI).

Today at JCVI West Greg is focused on helping to make advances in the new field of electromicrobiology. He, along with others in a team led by Professor Kenneth Nealson, measure long distance electron transport along bacterial nanowires (electrically conductive pili), such as those isolated from bacteria in wastewater, biofilms from pathogenic osteonecrosis of the jaw, and from other electrogenic species. He also uses microbial fuel cells to study the physiology of individual bacteria and complex biofilms, and he can determine the contribution to current production from individual bacteria and within biofilms. Greg and the team hope this work in optimizing microbial fuel cells will lead to new, advanced bioenergy applications.

While Greg misses the extreme seasons of Ontario, he admits that he likes the laid-back style of California, and says that he feels “good” about fish tacos. He has also been able to transplant some of his hobbies here, such as sailing and scuba (yes many people do pursue this sport in Canada since there are a lot of shipwrecks to explore in the Great Lakes).

Note:  Adapted from original article written by Gwynedd Benders of the JCVI Synthetic Biology research group.