Posts by JCVI Staff

La Jolla Community Celebrates Art and Science at Venter Institute Event

On Friday, September 12, the J. Craig Venter Institute (JCVI) hosted a reception at its La Jolla campus to celebrate the installation of “LIFE FORCE,” an original painting by San Diego-based artist and architect Fred Gemmell. This spectacular piece now hangs prominently in the entry of JCVI’s sustainable laboratory. Nearly 100 community leaders attended this beautiful evening which featured live music, award-winning wine courtesy of Coomber Family Ranch Wines, and delicious sushi from executive chef James Holder of James’ Place, the new restaurant at the La Jolla Playhouse.

JCVI is extremely grateful to Mr. Gemmell for his generous donation to the Institute. His work will serve as a daily inspiration not only to JCVI researchers but also to our community and the many visitors to our building. When asked about his inspiration for the work Mr. Gemmell said, “I try to capture, with complex detail and bold gestures, the amazing diversity and adaptability of life in all its interaction and beauty.” Gemmell employs a unique method of acrylic painting in reverse on museum quality, low-reflective plexiglass.

Fred Gemmell and Craig Venter

Fred Gemmell and Craig Venter looking at “LIFE FORCE.”

Reena Horowitz, Helene Gould, Jessie Knight, Eve Benton, George Gould

Reena Horowitz, Helene Gould, Jessie Knight, Eve Benton, George Gould

Peter Farrell, Betty Beyster and Craig Venter

Peter Farrell, Betty Beyster and Craig Venter

Ramin Pourteymour, Tara Tarrant, Linda Chester and Ken Rind

Ramin Pourteymour, Tara Tarrant, Linda Chester and Ken Rind

Bob Friedman, Jessie Knight, Peter Ellsworth

Bob Friedman, Jessie Knight, Peter Ellsworth

Katie Collins, Jack McGrory, Maureen and Skip Coomber

Katie Collins, Jack McGrory, Maureen and Skip Coomber

J. Craig Venter, Ph.D., JCVI Founder and CEO recognized this generous donation in remarks at the event saying, “Fred is a true visionary, and his art reminds me of how I think about science — abstract yet with bold and intended purpose. His incredible contribution is a testament to Fred’s passion for science and his fascination with the natural world. We couldn’t be more grateful for this addition to our new building.”

JCVI, a global leader in genomic research, has nearly 250 scientists engaged in a variety of important science programs including those focused on better understanding and improving human health and the environment. For more information about our research and how you can support us, please contact Katie Collins, Director of Development at kcollins@jcvi.org or 858-200-1847.

Understanding Complex Data through Better Visualization

Recently, researchers at JCVI reported on the Rhizoctonia solani mitochondrial genome which was the largest fungal mitochondrion to be sequenced to date. We showed that its unusually large size was probably due to the expansion of multiple genetic elements that populated the genome in somewhat of a ‘parasitic’ relationship. The visualization was meant to impress the number and variety of these repetitive genetic elements, and was selected in a commentary in  FEMS Microbiology Letters as an example of how to summarize molecular data in order to obtain an overall view of the results.

The outermost circle represents the chromosome and repetitive elements. Other important features such as genes, endonucleases, exons, RNAseq coverage are represented in the concentric circles respectively. Grey links represent short repeats (< 35bp) found up to 100 times in the genome; colored links show the location of repeats and follow the coloration in Track 1.

The outermost circle represents the chromosome and repetitive elements. Other important features such as genes, endonucleases, exons, RNAseq coverage are represented in the concentric circles respectively. Grey links represent short repeats (< 35bp) found up to 100 times in the genome; colored links show the location of repeats and follow the coloration in Track 1.

JCVI Research Impact

JCVI ranks in the top 1% of research institutions worldwide for research impact based on an analysis of Elsevier and Thompson Reuters data. The ranking was done by looking at institutional publication reach as seen through the number of citations referencing them.

Institution Excellence Rate
Broad Institute of MIT and Harvard 49.53
Whitehead Institute for Biomedical Research 47.92
Cold Spring Harbor Laboratory 41.64
Howard Hughes Medical Institute 41.62
Institute for Systems Biology 40.10
J. Craig Venter Institute 37.49
Wellcome Trust Sanger Institute 37.16
Harvard-MIT Division of Health Sciences and Technology 36.73
Salk Institute for Biological Studies 34.68
Institute of Electrical and Electronics Engineers, USA 34.14
Novartis Institutes for Biomedical Research 33.98
National Bureau of Economic Research 33.67
The Rockefeller University 33.40
European Molecular Biology Laboratory Heidelberg 33.28
Flanders Interuniversity Institute for Biotechnology 33.23
Novartis Pharma SA, East Hanover 33.20
Dana Farber Cancer Institute 32.95
F. Hoffmann-La Roche, Ltd 32.47
Group Health Cooperative 32.37
Microsoft Research Cambridge 32.08
International Agency for Research on Cancer 31.21
Nathan S. Kline Institute for Psychiatric Research 31.10
American Cancer Society 31.01
FOM Institute for Atomic and Molecular Physics 31.00
Medical Research Council 30.73
Scripps Research Institute 30.57
London Business School 30.51
World Health Organization Switzerland 30.38
Perimeter Institute for Theoretical Physics 30.32
Cancer Research UK 30.20

In a separate report Thompson Reuters published the “World’s Most Influential Scientific Minds 2014.” Seven JCVI scientists made the list, including: Daniel Haft, Lauren Brinkac, Scott Durkin, Ramana Madupu, Karen Nelson, Chris Town, and Weizhong Li.

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.

JCVI Hosts South African Scientists to Share Microbiome Research Techniques

Two scientists from the University of Cape Town, South Africa have joined Dr. Bill Nierman’s lab for the next month as part of NIH’s Human Heredity and Health in Africa (H3Africa) Initiative, a training program designed to build out technical biological skills in the African research community. This training relates specifically to developing techniques around the area of microbiome analysis, a relatively new field in the biological sciences.

Microbiome analysis for the collaborative study is looking at entire community of microorganisms in the respiratory tract of South African infants to better understand how the microbiome is associated with infant pneumonia and wheezing episodes. The expectation is that the organisms that reside in the infant respiratory tract will provide protection from or a predisposition to the pneumonia or wheezing episodes.

 

The Nierman Group

The Nierman group left to right Sarah Lucas, Bill Nierman, Shantelle Claassen, Mamadou Kaba and Stephanie Mounaud (unpictured Jyoti Shanker and Lilliana Losada) welcomes visiting scientists Ms. Classeen and Dr. Kaba from University of Cape Town for a month long training in microbiome sequencing and analysis.

Mamado Kaba, MD, PhD and colleague Shantelle Claassen from the University of Cape Town will be working closely under the guidance of JCVI’s Stephanie Mounaud who is functioning as the project manager and coordinating the laboratory components of a similar project at JCVI studying the microbiomes of inafnts in the Philippines and also in South Africa. These studies are sponsored by the Bill and Melinda Gates Foundation. The training will focus initially on preparing samples for DNA sequencing on a modern DNA sequencing platform, the Illumina MiSeq instrument. Once the sequence reads are off the sequencer, the instructional focus will shift to analysis of the reads by means of an informatics pipeline that develop phylogenies, or family trees, of the microbes that are obtained from the infant respiratory tract so that the abundance and relatedness of the microbes can be established. The bioinformatics training will be provided by Jyoti Shankar, the statistical analyst working on the Gates Foundation Project.

Mamadou Kaba is a Wellcome Trust Fellow working in the Division of Medical Microbiology, Faculty of Health Sciences, University of Cape Town. Mamadou’s research interests include the molecular epidemiology of infectious diseases and the study of human microbiome in healthy and disease conditions. He has contributed in establishing a new research group conducting studies on how the composition of the upper respiratory tract, gastrointestinal, and the house dust microbial communities influences the development of respiratory diseases.

Prior to joining the University of Cape Town, Mamadou worked as Research Associate at the Laboratory of Medical Microbiology, Timone University Hospital, Marseille, France, where he studied the epidemiological characteristics of infection with hepatitis E virus in South-eastern France.

Shantelle Claassen is pursuing a Masters degree in the Division of Medical Microbiology at the University of Cape Town. She has completed a BSc (Med) Honours degree in Infectious Diseases and Immunology at the University of Cape Town, during which she examined the relative efficacy of extracting bacterial genomic DNA from human faecal samples using five commercial DNA extraction kits. The DNA extraction kits were evaluated based on their ability to efficiently lyse bacterial cells, cause minimal DNA shearing, produce reproducible results and ensure broad-range representation of bacterial diversity.

Mamadou and Shantelle are currently involved in an additional prospective, longitudinal study of which the primary objective is to investigate the association between fecal bacterial communities and recurrent wheezing during the first two years of life.

Building the World’s First Net-Zero Energy Lab [video]

Building the World’s First Net-Zero Energy Lab

And see the construction in time-lapes.

Amazon Expedition

Yesterday, JCVI expedition scientist Jeff Hoffman embarked from Manaus on a sampling expedition of the Amazon River and its tributaries, which contains 1/5th of the Earth’s river flow. In collaboration with scientists Dr. Guilherme Oliviera and Dr. Sara Cuadros from the Centro de Excelencia em Bioinformatica (CEBIO) of Belo Horizonte, Jeff is taking samples to characterize the genomes of microbes found along 2/3rds of the entire Amazon watershed, including inflowing rivers from Manaus to Macapa. Our collaborators at CEBIO will be sequencing the samples with a joint Brazil-USA effort on analysis. Long recognized for the biodiversity of visible organisms, the Amazon is understudied with regards to the diversity of microscopic organisms and this expedition will substantially increase our understanding of the biological diversity on Earth. This work continues, leverages, and complements previous and ongoing JCVI work characterizing the unexplored microbiomes of marine, estuarine, freshwater, and terrestrial environments around the world.

See a gallery of the expedition on Facebook. More pictures will be added throughout the trip.

Carl Woese 1928-2012

Editor’s Note: This post originally appeared on T. Taxus, December 31, 2012, by Jonathan Badger. Dr. Badger  is an Assistant Professor in the Microbial and Environmental Genomics Group at the J. Craig Venter Institute in La Jolla, CA. Reprinted by permission.

As you may have heard, Carl Woese died of pancreatic cancer yesterday at the age of 84. I had the honor of working with Carl in grad school at the University of Illinois where my advisor, Gary Olsen, ran a joint lab with Carl.

Carl Woese

Carl Woese. Photo courtesy IGB.

As the originator of the use of ribosomal RNA to distinguish and classify organisms (including obviously the Archaea), Carl both revolutionized evolutionary biology and created a method that is still very much in use today. Even in the latest metagenomic study of the oceans or of the human gut, a 16S rRNA diversity study is required as a control in addition to whatever additional markers or random sequencing is used.

One of the things that fascinated me about Carl is how he constantly reinvented himself and explored new fields of biology — his early work in the 1960s dealt with classical molecular biology and the genetic code (the origins of which continued to fascinate him for the rest of his life). He then transfered to the study of the ribosome and its structure, which in turn led to his study of 16S and its evolutionary implications. In the 1990s, when I worked with him, he was a pioneeering microbial genomicist and collaborated with TIGR to sequence the first two Archaeal genomes. And in his final years he focused on early evolution and the last common ancestor of life in the light of what genomics has taught us.

Carl also had his humorous and counter-cultural side. I remember him telling me how his lab in the 1960s heard about the rumor that compounds in banana peels were a legal narcotic and how they launched an unofficial research project to isolate these. His verdict was that there was nothing there and neither the peels nor anything in them could get you high — but he wanted to empirically test that. Also, when reading about a supposed “Qi master” who claimed to be able to influence mutation rates with his mind, he invited him to the lab to give a demonstation — which naturally failed to show any effect under controlled conditions — but he wanted to see if the guy could really do it.

Genomics, metagenomics, and evolutionary biology has lost one of its greats — but his legacy lives on.

JCVI Viral Finishing Pipeline: a Winning Combination of Advanced Sequencing Technologies, Software Development and Automated Data Processing

JCVI viral projects are supported by the NIAID Genomic Sequencing Center for Infectious Disease (GSCID). The viral sequencing and finishing pipeline at JCVI combines next generation sequencing technologies with automated data processing. This allowed us to complete over 1,800 viral genomes in the last 12 months, and almost 8,800 genomes since 2005.

Viral Projects at JCVI

JIRA Viral Sample Tracking Workflow

Our NextGen pipeline, which utilizes SISPA-generated libraries with Roche/454 and Illumina sequencing, enables us to complete a wide variety of viral genomes including challenging samples. Automated assembly pipeline employs CLCbio command-line tools and JCVI cas2consed, a cas to ace assembly format conversion tool. Our complimentary Sanger pipeline software is currently being integrated with the NextGen pipeline. This will improve our data processing and will allow us to use validation software (autoTasker) more efficiently.

Assembly of Repetitive Viral Genomes

Genome Organization of Varicella-Zoster

Assembly of Novel Viral Genomes

CLC Assembly Viewer Representation

Promoter of Bat Genome

Promoter of Bat Genome

During the past year we have found that novel viruses, repetitive genomes, and mixed infection samples could not be easily integrated with our high-throughput assembly pipeline. We have developed an assembly and finishing process that utilizes components of the high-throughput pipeline and combines them with manual reference selection and editing. Using this approach we completed novel adenovirus genomes and mixed-infection avian influenza genomes, and improved assemblies of previously unknown arbovirus genomes. We are currently working on optimizing and automating this new pipeline.

Assembly of Mixed Viral Genomes

Consed Representation of Mixed Viral Sample

Consed Representation of Mixed Viral Sample

Repetitive genomes have long been known to present great challenges during assembly and finishing. We are presenting a new approach to assembly and finishing of repetitive varicella genome that is based on separating it into overlapping PCR amplicons followed by merging sequenced amplicons during assembly.

To streamline our viral pipelines, we have fully integrated them with JCVI’s LIMS and JIRA Workflow Management to create a semi-automated tracking interface that follows the progress of viral samples from acquisition through to NCBI submission. This allows us to process a large volume of samples with limited manual interaction and, at the same time, gives us flexibility to work on challenging and novel genomes.

Acknowledgements

The JCVI Viral Genomics Group is supported by federal funds from the National Institute of Allergy and Infectious Disease, the National Institutes of Health, and the Department of Health and Human Services under contracts no. HHSN272200900007C.

Bat coronavirus project is collaboration with Kathryn Holmes and Sam Dominguez, University of Colorado Medical Center.

The authors would like to thank members of the Viral Genomics and Informatics group at JCVI.

References

Viral genome sequencing by random priming methods. Djikeng A, Halpin R, Kuzmickas R, Depasse J, Feldblyum J, Sengamalay N, Afonso C, Zhang X, Anderson NG, Ghedin E, Spiro DJ. BMC Genomics. 2008 Jan 7;9:5A virus discovery method incorporating DNase treatment and its application to the identification of two bovine parvovirus species.  Allander T, Emerson SU, Engle RE, Purcell RH, Bukh J.

Note

This post is based on a poster by Nadia Fedorova, Danny Katzel, Tim Stockwell, Peter Edworthy, Rebecca Halpin, and David E. Wentworth.

Biowalk of Fame

There is a new “Biowalk of Fame” in Maryland, and our own Craig Venter was one of the first honorees receiving a plaque, which is there for all to see as you stroll through lovely Silver Spring.

Etching of Dr. J. Craig Venter on Biowalk of Fame

Etching of Dr. J. Craig Venter on Biowalk of Fame

Other honorees include Dr. Martin Rodbell and Ben Carson. The event to honor the awardees was on April 22, which also it happens to be Earth Day. Although it rained heavily throughout the event, there were a large number of people in attendance including several local government officials including Council member Valerie Ervin and Chairman Ike Leggett. Dr Martine Rothblatt, CEO of United Therapeutics, emceed the event.

Biowalk of Fame tour sign

Biowalk of Fame tour sign

The idea behind the BioWall and the Biowalk is very innovative. The Wall is a live movie like screen that allows videos from students and the public that relate to science to be continuously aired. A student observing a paramecium under the microscope for example can mail the clip in to United Therapeutics, and it will be available for all to see. The Biowalk also has plaques dedicated to those who have made the most outstanding contributions to the State of Maryland in the sciences – hence Craig.

Dr. J. Craig Venter's plaque on the Biowalk of Fame

Dr. J. Craig Venter's plaque on the Biowalk of Fame

Biowalk of Fame

Biowalk of Fame

The take home message is, if you are wondering through Silver Spring do not be surprised if you see Craig’s name on a plaque on 1040 Spring Street. Congratulations!