Posts tagged scientist spotlight

Scientist Spotlight: Anna Edlund, Ph.D.

Although Sweden is synonymous with Ikea, Volvo, meatballs and ABBA, the country has had a significant impact on science and discovery as far back as the 17th Century. Scientist Anna Edlund, Ph.D. who recently joined JCVI is another Swede pushing the boundaries of discovery in her new role as Assistant Professor, Department of Genomic Medicine.

Anna Edlund, Ph.D.

Anna Edlund, Ph.D.

Anna grew up in the middle of nature on a horse farm in the northern part of Sweden. Inspired by her country’s natural beauty and wilderness, she grew to care a great deal about the environment. During her first years at Södertörn University College she studied ‘green ecology’ and population genetics while she kept her job as a ranger for the Swedish Environmental Protection Agency working in a National park. Dr. Janet K. Jansson first introduced Anna to microbiology during an undergraduate course, and she immediately became fascinated with the unexplored world of microbes – she could not resist becoming a microbiologist. Anna finished her studies at the Karolinska Institute with a Master’s in microbiology and molecular biology. Under the guidance of Dr. Jansson, she pursued her Ph.D. studies in microbiology at the Swedish University of Agricultural Science in Uppsala. Between 2002 and 2007, she studied marine biology specifically exploring the microbial life in sediments of the Baltic Sea. She continued her education in marine microbial ecology as a Postdoctoral Scholar at Scripps Institute of Oceanography at the Center for Marine Biotechnology and Biomedicine, and ultimately returned to Sweden as an Assistant Professor at the Department of Systems Ecology at Stockholm University.

Anna’s trajectory changed in March 2012 when she returned to California at the invitation of Dr. Jeff McLean, a former JCVI scientist and pioneer in the human oral microbiome. As a Project Scientist and Postdoctoral Fellow at UCLA’s School of Dentistry and JCVI, Anna turned her focus from studying bacterial ecological functions in the marine environment towards understanding the role of the oral microbiome in human health.

As a scientist at JCVI, Anna’s research focuses on the complex human oral microbiome and how bacterial gene expression and signaling molecules orchestrate the development of both health and disease associated communities. Anna joined the team at JCVI to work with world-leading experts in microbiology in an environment where most of her time can be spent doing research.

Recently, Anna received a three-year award of $750,000 from the National Institute of Dental and Craniofacial Research (NIDCR) to investigate oral pathogen virulence within complex oral biofilm communities. Her goal is to deepen our knowledge of the molecular processes of oral biofilms during stress and disease-like conditions (e.g. pathogen invasion, low pH). She hopes her findings will lead to improvements in treating and preventing oral diseases.

Scientist Spotlight: Sinem Beyhan, Ph.D.

Sinem Beyhan, Ph.D. recently joined the JCVI team as an Assistant Professor in the Department of Infectious Diseases and is working closely with Dr. Bill Nierman, Director of JCVI’s Infectious Diseases Program to expand our studies on fungal pathogens. Sinem is interested in understanding how pathogenic fungi can sense and respond to their environment and cause disease. Her current focus is investigating how the fungal pathogen Histoplasma capsulatum uses mammalian host temperature as a signal to alter cell morphology and virulence traits to infect human and mammalian hosts.

Dr. Sinem Beyhan

Dr. Sinem Beyhan

Sinem was born in Turkey. At a young age, she was infinitely curious about the world around her, asking how and why at every opportunity. She was a successful student and was supported by her parents and teachers. Sinem’s early exposure to science was limited. Growing up she did not have access to science camps or scientific experimentation in the classroom. Although culturally girls were pushed away from science and engineering studies, Sinem never heard “no” or “you can’t.”   During high school biology she began her exploration of how organisms work. Even though the class was all memorization, Sinem’s teacher encouraged her to ask questions and to study. Sinem attended the Middle East Technical University in Ankara, Turkey to study genetics and molecular biology. She decided to focus on microbiology and left Turkey for the University of California, Santa Cruz (UCSC) in 2003.

At UCSC, Sinem would begin her investigation of pathogens. During this time she focused on Vibrio cholerae, the etiologic agent of the disease cholera. Another significant event occurred during her time at UCSC, Sinem met her advisor Dr. Fitnat Yildiz. Dr. Yildiz also happened to be a Turkish woman, and the two researchers clicked immediately. They published 14 papers together. After receiving her Ph.D. in Microbiology and Environmental Toxicology, Sinem decided to stay in the United States. She moved to the University of California, San Francisco for her postdoctoral research. Here, Sinem would be mentored by Dr. Anital Sil, and she would shift her focus to fungal pathogens.

After being mentored by scientists like Drs. Yildiz and Sil, two intelligent women who inspired Sinem and showed her that it is possible to balance research and a family, it is not surprising that Sinem also thrives in the role of adviser. She has mentored students throughout her graduate and postdoctoral posts. In addition to establishing her lab at JCVI, Sinem’s is excited to be part of the training programs at JCVI. She also wants to inspire students and interns to pursue a career in science. Although Sinem jokes that her mother now wishes she had told Sinem “no” when she wanted to leave Turkey (it is challenging being so far from her family), it is clear that our new scientist will continue to encourage her team and interns that they “can.”

In addition to uncovering the mechanisms of fungal pathogens, Sinem is also passionate about running, scuba diving, and playing games with her 1-year-old daughter.

Scientist Spotlight: Meet Sarah Highlander

Sarah Highlander Ph.D. is an esteemed scientist and professor who joined JCVI in La Jolla this year. She comes from a long line of academically successful Professors, including a great uncle who was a University Dean. As a young child, Sarah was influenced by her parents: her mother was a musician and her father was a Ph.D. chemical engineer. Sarah too was a musician and she still enjoys jazz and the opera. But it was her father’s scientific career that influenced her own decision to pursue scientific research as her career.

Dr. Sarah Highlander

Dr. Sarah Highlander

As a chemical engineer and early IT specialist, he shared his interests with her at the kitchen table by doing mathematical puzzles and simple experiments. They explored the impact light had on grass growth by placing plants in the closet. Then in high school, she had the opportunity to work on a microbiology project with the help of her father. Using agar slants from his colleague’s lab, she looked for antimicrobial features of bacteria in the soil. Even with these opportunities, her focus in the sciences wasn’t fully set until she began working as a technician in a fermentation research lab where she had the opportunity to work with plasmids after completing her bachelor’s degree. At this point, plasmids and restriction enzymes were not readily available and researchers had to isolate them in their labs. She was extremely successful as a technician and even published several papers and secured several patents.

This experience launched Highlander into Medical Microbiology. She went to the Sackler Institute of Biomedical Sciences at the New York University School of Medicine, where she earned her Ph.D. in 1985. With her curious nature and the bourgeoning field of biotechnology, she began to research the replication of DNA plasmids in Staphylococcus. She asked basic but as yet unanswered questions such as, “How are these molecules controlled in the cell?” and “How can they best be manipulated in the laboratory?” Her thesis involved characterizing small RNA molecules that control plasmid copy number.

During her Post-doctoral fellowship, she shifted her focus to infectious diseases and worked on vaccine development for a cattle disease called “shipping fever” at the University of Texas Health Science Center. Shipping fever is the most common and costly problem affecting calves. It accounts for major economic losses to the cattle producer by reducing average daily weight gain, impairs feed efficiency, and diminishes overall performance and health of beef calves. Vaccination is key to reduce the disease and Highlander’s research culminated in the development of a subunit vaccine that is still in use.

After her fellowship, she began her professorship at Baylor’s College of Medicine (BCM), where she continued her research into shipping fever. The primary bacterial agent in this disease is Mannheimia haemolytica, which is the same family as the human respiratory pathogen, Haemophilus influenzae. JCVI scientists were the first to sequence and publish the H flu genome in 1995. Dr. Highlander’s group performed extensive characterization of the M. haemolytica leukotoxin and developed numerous genetic tools for manipulation and tagging of the organism. She holds patents for subunit and live-attenuated vaccines to prevent shipping fever.

In 2002, Highlander founded Prokaryon Technologies, a for-profit company focused on animal health to prevent and control diseases associated with food animals. One of Prokaryon’s lead products was a genomics-derived vaccine to prevent shipping fever in cattle.

While leading and growing her company, Highlander stayed committed to her academic research interests and joined the Human Genome Sequencing Center at Baylor. At BCM, she participated in genome sequencing of several pathogens (including M. haemolytica) and she moved to focus more on human pathogens. From 2006 to 2013, Highlander was a principal investigator for the Human Microbiome Project (HMP), a National Institutes of Health-funded program in which JCVI researchers were also key leaders.

In addition to her research, Highlander was involved in graduate and medical education at BCM. She was the co-director of the departmental graduate program for 15 years and directed and taught courses focused on bacterial physiology and molecular laboratory methods. Preparation for lectures and interactions with students helped her stay on top of new techniques and research, which in turn helped her further her own research. Sarah had the opportunity to mentor many graduate students both formally and informally.

At JCVI, Highlander is continuing her work on the microbes that live in and on the human body. Specifically she and her team are looking at the complex microbial communities that live in the human gut. While many microbes are associated with disease, most in the human body are associated with health. Highlander and her team are working to develop specific healthy bacterial mixtures that could be used treat conditions such recurrent Clostridium difficile diarrhea, inflammatory bowel disease and others. She is also using bioinformatics tools to look for new causes of diarrhea. “I am delighted to be a part of the collaborative environment here at JCVI and to be surrounded by colleagues who share common interests in bacterial genetics, genomics, microbial physiology and pathogenesis. The microbiome group at JCVI is strong and I hope to be able to make significant contributions to ongoing and future projects here”.

Even in her personal life, Sarah researches, through her hobby of tracing her genealogy. She has been able to find family roots dating back to the 1500s. This detective work is challenging but it keeps her mind sharp and detailed oriented. She points out that learning family naming patterns can be critical to genealogy research just as algorithm development is to genomic research.

Never having lost that early scientific curiosity and excitement of discovery that her father instilled in her as a young girl, Sarah loves working in the laboratory at JCVI and asking questions. Her analytical and inquisitive nature is one of her greatest professional strengths. She is fascinated by the complexity of the microbial ecosystem in our bodies and the impact these microbes have on our health. As she says, “Microbes are going to continue to win through evolution. We need to figure out the next step to keep ahead!” Let’s hope Highlander and her team can win this battle.

Scientist Spotlight: Meet David Wentworth

During the height of the H1N1 Flu pandemic, David Wentworth was running a microbial genetics laboratory at the Wadsworth Center, New York State Department of Health (NYSDOH) where he was instrumental in developing a method to amplify influenza genomes regardless of strain using “universal primers” or short strands of DNA that recognize conserved segments across the genomes of many different flu strains. This amplification process was developed to generate recombinant influenza A viruses (the most common flu type affecting humans and animals) that could be used for the production of new vaccines. From a clinical swab it took his team 9-12 days to develop vaccine seed stocks. It was this work that first brought Dave to JCVI’s attention.

Several years ago Dave began collaborations with JCVI scientists to sequence human and avian influenza viruses. The collaborations intensified two years ago when all pandemic flu samples (or suspected flu samples) were first sent to Dave’s lab so the virus could be amplified in sufficient quantities for sequencing using his new amplification pipeline. The amplification took only a day and then isolated, non-infectious, DNA was sent to JCVI for sequencing. JCVI was the natural choice for this work since we are host to the government-funded “Influenza Genome Sequencing Project,” with the goal of sequencing large numbers of viral genomes to help scientists worldwide to understand how flu viruses evolve and cause disease. JCVI researchers then deposited influenza sequences into GenBank within two days of receiving DNA from Dave’s lab, enabling researchers worldwide to track what strains are circulating and how they are evolving. JCVI has sequenced over 75% of the influenza genomes in GenBank, the NIH public repository for sharing genetic sequencing data.

Influenza Genome Amplification Directly From Clinical Specimens

Influenza Genome Amplification Directly From Clinical Specimens (Zhou, B., M. E. Donnelly, D. T. Scholes, K. St.George, M. Hatta, Y. Kawaoka, and D. E. Wentworth. 2009. J.Virol. 83:10309-10313.).

Dave was soon invited for a talk at JCVI. “The opportunities at JCVI were to help build the [viral genomics] program. And already good, quality people are here studying viruses with a focus on viral evolution and sequencing analysis,” Dave remarked. “Being part of generating that information, I think makes you have a better feel for the biology.” The capabilities for viral sequencing combined with IFX strengths and the interest in viral evolution at JCVI was a draw for Dave and he soon joined the team. Moreover, there are opportunities at JCVI to work with collaborators who send specimens from various regions of the world for sequencing so that we can “more deeply understand the mutations that contribute to virulence,” he said. He is particularly interested in antigenic drift (how viruses escape immunity) that contributes to the “annual influenza escape,” which is critical in developing vaccine strains.

New Live Attenuated Vaccine Approaches

New Live Attenuated Vaccine Approaches. Figure shows influenza RNA polymerase activity (GFP) at various temperatures. Mutations engineered into the genome (PB1-Mut3, PB2-Mut4) synergize and inhibit replication at higher temperatures of the lung (37 C) or fever (39 C).

The need for new and improved methods to develop vaccines, coupled with the advances in synthetic genomics developed at JCVI led to the formation last year by JCVI and the company Synthetic Genomics Inc. of a new company, Synthetic Genomics Vaccines Inc. (SGVI). JCVI scientists, through SGVI, are working on a three-year collaboration agreement with Novartis to apply synthetic genomics tools and technologies to accelerate the production of the influenza seed strains required for vaccine manufacturing. The agreement, supported by an award from the U.S. Biomedical Advanced Research and Development Authority (BARDA), could ultimately lead to a more timely and effective response to seasonal and pandemic influenza outbreaks. The idea is to create viruses de novo or synthesize genes critical for its antigenicity and put these in normal vaccine strains for production. The goal of the work at SGVI is to synthesize a virus in one week, or rather a seed stock, which still needs to be amplified in big fermenters. New seed stocks take 3-4 weeks to produce which is currently a rate liming step.

You don’t hear too many people singing its praises and saying “I love the flu!” as Dave has remarked, but put in context, his enthusiasm for his work shines through best when talking about his love of teaching. He gets excited teaching young scientists about virology, especially helping them to understand the important areas to study, and where the research will lead to solve a major problem. “The rewarding part of being a mentor is to see all of the people who have found their niche – it might not be bench research but they are still carrying knowledge with them.”

David Wentworth DEW checking a hive in the late Spring.

David Wentworth DEW checking a hive in the late Spring.

Aside from spending time with his family, Dave enjoys a hobby started by his dad – to cultivate honey bees. A community gardens group at a middle school in Albany, NY was looking for bees to pollinate their plants. Dave spearheaded the effort and used it as a learning tool for kids, who helped feed honey to caterpillars and moths. He also used to give lectures on bee cultivation and has taught college courses in animal science. Dave’s enthusiasm for science among his students and peers could be considered infectious, just like the subject of his research!

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.

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.

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.