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.

Trapping Microbes 750 miles north of the Arctic Circle

About 1% of all microbes are “culturable” in the lab. They are some of the most stubborn organisms requiring special and specific nutrients as well as optimal temperatures and conditions. So, how do we get the “unculturables” to be “culturable”? We make bacteria “traps”, where we take media, sandwich them between a membrane that cannot be penetrated by bacteria and another membrane that can be penetrated by bacteria. Bacteria can grow and migrate toward the trap and essentially get stuck within the membranes and we can cultivate them afterwards. What about bacteria that don’t migrate? We can account for these bacteria by taking them out of the soil, placing them in media and putting them back into the environment using devices called diffusion chambers. These diffusion chambers consist of two membranes that are able to hold bacteria and media yet are porous enough for nutrients and ions. Using these techniques we have already cultivated more than 15 previously uncultivated species. For year two of this project we intend to cultivate at least 90 new species for whole genome shotgun sequencing. WGS data from such new species will be incredibly useful in determining which metabolic pathways are present to allow these organisms to survive in such a harsh barren climate.

Diffusion Chambers

Diffusion Chambers

Setting Bacterial Traps

Setting Bacterial Traps

Traps Under Water

Traps Under Water

Thule, Greenland Year Two

Sequence data from the previous year allowed us to determine the overall microbial population in each site and this year we decided to focus on the Rich Lake site which seem to have representation of nearly all microbes found in the other sites. So lucky for us we only had to work on one site this year rather than six. This in itself had me excited to go back to Thule. After a five-hour flight on a military plane from BWI I finally arrived to Thule Greenland where we were greeted by the Colonel as well as other high ranking military officials at the hanger. Once I cleared the customs processing area, I arrived to the dorm where the other scientists were living. It was a little different from last year’s accommodations but nevertheless the luxuries of WI-FI, Internet and cable TV were all available. As I am anxious to get to the field and see the changes in the Rich Lake site, we were given some interesting news. That day was not a good day to travel to the site because a mother polar bear and her two cubs were spotted nearby not too long ago by military police. However, we managed to get other work done by preparing the schedule for the sampling, cultivation and other labwork.


The next few days consisted of preparing culture media, cultivation traps and diffusion chambers, and going out into the field (polar bear spray in hand; yes it’s a real thing!). We were extra careful in the field since there was quite a bit of fog in the area that did not seem to go anywhere and fog happens to be the same color as polar bears. The fog did however make it a bit easier to sleep since most of the sunlight was covered and when there’s 24 hours of daylight from mid-April until September, a little fog can still serve a purpose.

Rich Lake Site

Rich Lake Site



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.

Professional Development Opportunities this Summer

This summer we are offering two professional development workshops: GenomeSolver and Bioinformatics: Unlocking Life through Computation.  Both explore bioinformatics, microbial diversity and the implementation in the undergradauate or high school classrooms. 

The GenomeSolver workshop trains faculty on genome analysis. Workshop attendees will learn about general methodologies, standards, and processes used to annotate and analyze microbial genomes. The workshop contents will be available to aid the faculty in developing teaching modules. In addition, extensive documentation on methodologies and tools will be available via the online environment created for this project. On online web portal Genome Solver (www.genomesolver.org) will be a virtual space for development and sustaining of community. Genome Solver will assist faculty with technical issues and curricular design, as well as an online environment for the ongoing sharing of information including publication of student work. 


Bioinformatics: Unlocking Life through Computation is a new opportunity for high school teachers. Genomics and biotechnology are valuable tools in our quest to understand life and nature. However, introducing the science classroom to the computational and mathematical underpinnings of biology can be challenging. The goal of this workshop is to introduce a curriculum for mathematics and science education in the area of genomics (with a focus on the fascinating world of microbes). Educators will be introduced to the various analysis and computational challenges that arise in this discipline. Workflow examples illustrating comparative genomic analysis will be made available through the JCVI Metagenomics Report (METAREP) software infrastructure. The eventual aim is for the educational material to be integrated with local high school curricula requirements to expose students to both hypothesis-driven and discovery-based science.


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.

The 2014 Summer Internship Application is Open and Announcing the Genomics Scholar Program

The 2014 Summer Internship Application is now open.   Last summer, we hosted 49 interns from a pool of 424 applicants. They presented their research in the First Annual Summer Internship Poster Sessions held in San Diego and Rockville. The posters were judged by a team of volunteer JCVI scientists and the poster sessions were open to all employees, interns and their guests to share what great work they all participated in this summer.



2013 Intern Poster Session

2013 Intern Poster Session

We are also excited to announce the new Genomics Scholar Program beginning this summer and also accepting applications.  The Genomic Scholar Program (GSP) is a targeted research experience program to community college students in Rockville. Our program incorporates multiple avenues of support for students through the research experience with the Principal Investigators as mentors, and supplemental professional development provided by the JCVI.  Additionally, selected students will have the opportunity to participate in undergraduate research conferences.

The GSP is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number R25DK098111.