Posts by JCVI Staff

Ocean Sampling Day 2018

J. Craig Venter Institute (JCVI) scientists, led by Lisa Ziegler Allen, PhD, are collaborating with Kelly Goodwin, PhD (NOAA), Brian Palenik, PhD (UCSD), and Maitreyi Nagarkar (UCSD) to participate in this years’ Ocean Sampling Day on June 21. The team, which also includes Sarah Schwenck and Ariel Rabines from JCVI, is sampling the water off the pier at Scripps Institution of Oceanography (SIO).

Ocean Sampling Day participant sites since 2014.

Ocean Sampling Day (OSD) is an international effort to simultaneously sample the world’s oceans in one day, with the first such event happening in 2014. Following the success of the first event, the OSD consortium has held an event each year since, with continued long-term support from the EMBRC ERIC infrastructure.

Ocean Sampling Day 2014 with local Girl Scout groups.

JCVI Global Ocean Sampling Program

JCVI has a long history of ocean and environmental sampling, beginning in 2003 with a pilot study in the Sargasso Sea. This led to a two-year effort where JCVI scientists circumnavigated the globe, covering a staggering 32,000 nautical miles, visiting 23 different countries and island groups on four continents. Millions of new genes and nearly 1000 genomes for uncultivated lineages of microbes, as well as a more comprehensive understanding of marine microbiology through community datamining resulted from this historic project. JCVI has been engaged continually in these efforts since, culling the oceans, rivers, lakes, soil, and air to learn about the distinct microbial communities that inhabit each.

J. Craig Venter Institute Education Program Fosters Learning Opportunities with Salisbury University Students and Faculty

Patti Erickson, PhD first connected with the J. Craig Venter Institute (JCVI) in the Fall of 2016 as an associate professor at Salisbury University looking for opportunities to expose undergraduate students to biology outside of the classroom. Soon thereafter, she and a group from Salisbury visited JCVI’s Rockville labs, forging a relationship that would lead her to working in the lab of Sanjay Vashee, PhD as a visiting scientist while on sabbatical.

Her work at JCVI, which is ongoing, is focused on using synthetic biology techniques developed at JCVI to generate partial genomic hybrids of Mycoplasma gallisepticum to facilitate functional analysis of this important poultry pathogen. Serendipitously, Salisbury University is located on the Eastern Shore of Maryland, known for its large-scale chicken breeding and home to Perdue Farms.

Dr. Erickson presenting an overview of the history of JCVI’s Mycoplasma research and her work on the Mycoplasma gallisepticum to the Salisbury University group touring JCVI Rockville.

This past month Dr. Erickson and Salisbury students traveled to San Diego to attend the annual American Society for Biochemistry and Molecular Biology (ASBMB) meeting, held in conjunction with the Experimental Biology conference. There, she presented her work involving C. elegans, done while working in the Hawdon Lab at George Washington University, and Salisbury students presented posters on independent research projects.

While in the San Diego area, the group was able to visit JCVI’s La Jolla campus, where they were hosted by Gene Tan, PhD. They visited with leading synthetic biology experts including John Glass, PhD, who gave an overview of the minimal cell project, followed by Nobel Laureate Hamilton Smith, MD and Clyde Hutchison, PhD. They also toured the facility, which is an ultra-energy efficient laboratory.

Salisbury University students and faculty, and J. Craig Venter Institute staff gather at the end of the day’s activities at JCVI’s Rockville location.

Salisbury students and faculty again visited JCVI Rockville this past week for a full day of lectures and demonstrations. JCVI’s Stephanie Mounaud presented on an infant microbiome project; David Haft presented on hidden Markov modeling approaches; and Dr. Erickson gave an overview of JCVI’s Mycoplasma research and how her work on the M. gallisepticum genome hybrids fits into it.

Students from Salisbury University tour JCVI’s Rockville lab. Left: Dr. Chandran shows the group mammalian cell lines. Right: Dr. Yu discusses mass spectroscopy.

Other scientists led a lab tour, including Yanbao Yu, PhD, who explained how mass spectroscopy can be used to identify and sort peptides for proteomics studies. Agnes Chan, PhD showed the group the MinIon nanopore sequencer and discussed forthcoming technologies that will make sequencing financially feasible at smaller universities. Suchismita Chandran, PhD discussed the importance of mammalian tissue cultures for studying viruses and showed the group several cell lines, while Bryan Frank discussed the airplane microbiome project. The visit culminated with Nacyra Assad-Garcia describing the challenges of transplanting entire Mycoplasma genomes.

The visits were organized by JCVI’s education manager, Sarah Grimshaw. Educational outreach and community engagement are part of JCVI’s core mission. JCVI is committed to enhancing scientific literacy, increasing enthusiasm in science, and developing the next generation of genetic and genomic scientists. To learn more, visit JCVI’s Educational Outreach page.

J. Craig Venter Institute Makes Strides in Microbial Analysis of Artwork which May Lead to Better Preservation Techniques

Through the Leonardo da Vinci DNA Project, researchers at J. Craig Venter Institute (JCVI), led by Karen Nelson, PhD, began taking environmental samples from different pieces of aging artwork with the aim of understanding which microbial species are present on varying surfaces and how these communities affect preservation efforts. This area of research also has broader forensic archaeological implications. JCVI hopes to use these methods to study Renaissance period artwork in the near future.

The speakers and participants of the Leonardo da Vinci DNA Project May 2018 Conference.

This past week the Leonardo DNA Project team met in Florence, Italy where they held public lectures on the overall progress of the project and to plan next steps. Findings from the microbial analysis component of the project, for which JCVI is responsible, were presented by Manolito Torralba.

One-hundred forty-two art surface samples were catalogued, the first of which was taken in December of 2015 and the second group in May of 2017. Each work sampled had on average three sites tested. The base materials for the works includes stone, wood, canvas, metal, and plaster—some of which were painted on.

Artwork sampled in May of 2017 from a private collection.

Using a statistical modeling process, principle coordinate analysis (PCoA), researchers have shown that samples from the same substrate, or base material, cluster and that there is some overlap between stone/marble and wood microbial communities.

JCVI researchers report that oil degrading species are present on canvas areas in deteriorated states. Additionally, oxidase positive organisms, which may be responsible for further breakdown in the art, are in high abundance on painted surfaces.

Additional samples from May of 2017. In total, there were 96 swab samples collected at this time (48 DNA and 48 RNA).

Future aims of the microbial analysis component of the project include 1) expanding they types of art being sampled to include fresco, painting on animal hides, other stone types, and glass; 2) confirming the presence of oxidase positive elements through metagenomics and metatranscriptomics sequencing; 3) identifying fungal species using molecular markers; and 3) using genomics to identify authenticity and geographical origin of works of art.

Project Background

The Leonardo DNA Project’s broad aims are to conclusively determine if the remains purported to be those of Leonardo da Vinci at Amboise Castle are his, by comparing DNA profiles to those of known relatives. Additionally, it will look at genetic markers using whole genome sequencing from Leonardo’s remains to better understand his extraordinary talents and visual acuity through genetic associations. Also, using novel informatics approaches researchers will create three dimensional images of Da Vinci using the genome sequence data.

Funding for this project provided by The Richard Lounsbery Foundation.

BioVision Alexandria 2018

The BioVision Alexandria conference convened at the Bibliotheca Alexandrina, in Alexandria, Egypt this past April. The Bibliotheca Alexandrina is a commemoration of the Ancient Library of Alexandria and an attempt to rekindle the global cultural and scholarship role of the library.

Dr. Nelson delivering the keynote address at BioVision Alexandria.

With this backdrop, BioVison joined scientific and other leaders spanning disciplines to meet and listen to presentations on the most pressing challenges relating to poverty and human health. Among the distinguished participants was JCVI president, Karen Nelson, PhD, and senior scientist at JCVI and associate professor at the American University in Cairo, Ahmed Moustafa, PhD.

In 2015, through the United Nations Department of Economic and Social Affairs (UN DESA), a set of seventeen sustainable development goals (SDGs) was outlined and adopted by the international community. In keeping with these targets, BioVision’s theme this year was “New Life Sciences: Towards SDGs.”

Dr. Nelson meeting with BioVision conference participants.

In her keynote speech, Dr. Nelson spoke broadly about the impact of genomics and advances in microbiome research that may have significant impact on our ability to achieve and sustain these goals. Dr. Nelson also met with next-generation scientists, MS and PhD students from the Middle East and Africa and discussed topics from scientific and technical to career advising and opportunities.

Dr. Karen Nelson and attendees of her lecture at the American University in Cairo.

Other conference topics included open data, precision medicine, drug discovery, environmental genomics, synthetic biology, as well as the supporting framework provided through policy and economic reforms. The conference also focused on the need to foster scientific discovery in developing countries. Of the 25 represented nations in the speaking lineup, about half were developing countries.

After the conference, Dr. Nelson visited the American University in Cairo (AUC) in New Cairo where she gave a public lecture on genomics and health. The lecture went over the history of genomic technologies and discoveries and the envisioned future role of genomics in clinical diagnosis and therapeutics.

During her visit to AUC, Dr. Nelson met Dr. Yehia Zakaria Gad, the head of Ancient DNA in the Egyptian Museum. They discussed several potential venues of collaboration between JCVI and the Egyptian Museum.

Dr. Nelson also joined Dr. Hassan El-Fawal, Dean of AUC’s School of Sciences and Engineering, and graduate students from the engineering and sciences departments for a discussion on the critical role of bridging communications between scientists and engineers to advance improvements to the quality of human life.

J. Craig Venter Institute Inspires Kids on “Take Your Child to Work Day”

Last month when my kindergarten-aged daughter brought home a note from school to dress up as their future career choice, I was pleasantly surprised to hear from her that she aspired to be a scientist just like me. So, we dug through my clothes and found her an old lab coat and decorated the collars with some biology-themed pins. When I heard JCVI was hosting a “take your child to work day” I knew she would be very excited to visit. She and the other children were greeted with hands-on activities meticulously planned by JCVI’s education manager, Sarah Grimshaw. Sixteen elementary and middle school children accompanied their parents to work at the Rockville, MD site to learn about JCVI’s research.

To kick off the day Brett Pickett, PhD opened with a genomics primer.

The event included talks and hands-on experiments that were both informational and engaging for the children. JCVI scientists Brett Pickett, PhD and Hernan Lorenzi, PhD described some of the interesting research being conducted at the institute. The children were introduced to the concepts including DNA, nucleus, and the cell. They were especially excited when they were invited to stain the nucleus of human cells themselves and view them under the microscope with me and David Brown, PhD.

The highlight of the day may have been when the children actually extracted DNA from strawberries in a tube. The realization that their food is made up of DNA was a thought-provoking fact that they mulled over during lunch. Of course, nothing could top the double helix model of the DNA that they created for dessert with Twizzler candy and marshmallows. The kids were very proud of their DNA art. Peppered through all the DNA activity, the children also learned about bacteria and fungi, and the consequence of personal hygiene through hand-washing experiments with Stephanie Mounaud. They also enjoyed making slime and elephant toothpaste and discussed about the significance of chemical reactions.

Sarah Grimshaw and David Brown, PhD work with the group on extracting DNA from strawberries.

The children were very excited about their day and seemed to enjoy their experience at JCVI. Several of them were overheard saying that it was one of the best days of their lives – a sentiment that the staff and scientists at JCVI also shared. While the JCVI “take your child to work day” was a successful event, I didn’t realize how much of an impact it had made on the minds of these kids until I heard my daughter describe the double helix model of the DNA to her dad later in the evening with all its components and structural details. She even enthusiastically declared that she wanted to work as a scientist at JCVI (just like her mother), which made me appreciate JCVI’s commitment to educational outreach efforts and public engagement.

Still excited from the day’s events, the group poses with their double helix candy models.

With the current environment of science education, it has become critical for institutions like JCVI to take up the mantle to help provide the knowledge, resources, and inspiration to the younger generation in the STEM field. As a parent and a scientist, I am glad that my child had the opportunity to experience some interesting science during this event, and hope to continue to be a part of JCVI’s mission to motivate budding scientists.

Suchismita Chandran, PhD
Staff Scientist, Department of Synthetic Biology and Bioenergy, JCVI

JCVI to Receive Grant from Chan Zuckerberg Initiative to Define the Language of Human Cell Classification

Researchers at J. Craig Venter Institute (JCVI), led by Richard Scheuermann, PhD, director of JCVI’s La Jolla Campus, have been awarded a grant from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation as part of the Human Cell Atlas project. JCVI will be building on our previous work in developing an expanded human cell ontology that scientists can use to classify cells and effectively communicate among one another.

On average there are around 30 to 40 trillion cells in the human body. Historically, cell types were defined by “low-resolution” experiments that identified characteristic features, such as anatomic locations, cellular structures, or cellular functions.

Technological advances have significantly increased the resolution and rate at which we are capturing data, leading to discovery of new cell types at an unprecedented rate. This rapid pace of discovery has revealed serious bottlenecks in our ability to define cell types for comparison across studies.

Through this new grant JCVI scientists will  develop minimum information standards, and statistical cell data matching approaches that scientists can use to describe human cells, using data from emerging technologies.

“Single cell genomics is revolutionizing our understanding of the cellular complexity of biological systems,” said Dr. Scheuermann. “We now need to expand our language for describing the different types of cells being identified so that scientists can share their discoveries in a meaningful way. This new project supported, by the Chan Zuckerberg Initiative, will allow us to develop and disseminate these basic language tools to support this scientific knowledge sharing.”

Human cell classification is part of a broader Institute initiative focusing on single cell genomics. JCVI has been at the forefront of laboratory and computational genomic advancements since its founding, and is now applying this knowledge to a number of projects through the recently founded Center for Single Cell Genomics, including exploring the cellular complexity of the human brain, identifying abnormal cells driving autoimmune disease, and discovering the cellular determinants of effective vaccine responses.

About the Chan Zuckerberg Initiative

The Chan Zuckerberg Initiative was launched in December 2015 by Mark Zuckerberg, founder and CEO of Facebook, and Priscilla Chan, a pediatrician and founder and CEO of The Primary School in East Palo Alto. The Chan Zuckerberg Initiative is a new kind of philanthropy that seeks to engineer change at scale. By pairing world-class engineering with grant-making, impact investing, policy, and advocacy work, CZI hopes to build a future for everyone. Initial areas of focus include supporting science through basic biomedical research and education through personalized learning. CZI is also exploring ways to address barriers to justice and opportunity – from criminal justice reform, to expanded access, to economic opportunity and affordable housing.

J. Craig Venter Institute Teaches Students about Genomics at Annual High Tech Fair

In January, JCVI was one of more than 40 San Diego STEM-related organizations who participated in the Fleet Science Center’s annual High Tech Fair. This year more than 3,000 local middle and high-school students, their teachers, and families descended upon Balboa Park throughout the two-day event to engage in exciting and interactive educational experiences. Students learned about local research being done in a variety of fields and had the opportunity to speak with scientists about career opportunities.

Fleet Science Center’s annual High Tech Fair

Students who visited the JCVI booth learned about the range of our genomics research by engaging in some tasty (or not…) hands-on activities. They participated in a taste-test experiment to learn about one of their own inherited traits by discovering, almost shockingly at times, their phenotype of TAS2R38, a gene that encodes for bitter taste.

To do this they tasted phenylthiocarbamide (PTC), a compound responsible for bitter tastes similar to what is found in Brussel sprouts and cabbage (members of the Brassica family). About 70% of the population are “tasters,” and can taste some degree of bitterness in PTC.

The students then learned why by looking at the different genotypes of tasters and non-tasters by locating the variants in a DNA sequencing read.

A student reaches in for a tasting strip to see if she can detect the bitter tastes of phenylthiocarbamide (PTC).

Lastly, to help alleviate the bitter taste and to help learn about the structure and components of DNA, students built edible double helix models out of red licorice and marshmallows.

Students assemble sweet double helix models to erase any bitterness left from the experiment.

This year’s High Tech Fair was a great success; we had an incredible time talking to students about science and learning about their career aspirations. We are looking forward to next year’s event already!

Dr. Scheuermann featured on the Illumina Genomics Podcast

In Episode 14 of the Illumina Genomics Podcast, Dr. Richard Scheuermann is the featured guest. Dr. Scheuermann discusses advancements in cell ontology, informatics, machine learning, and how his approach to biology has adapted over the years to incorporate the massive increases of data and advancements in computing power.

Listen to Episode 14: Single-Cell Genomics and Cell Ontology

New Method for Genome-wide Engineering of Viruses

Researchers at JCVI have been developing synthetic genomics assembly methods since 2000, addressing fundamental biological questions. Together, with researchers at Oregon Health and Science University, Johns Hopkins University School of Medicine, Synthetic Genomics, Inc., and Vir Biotechnology, Inc. (formerly TomegaVax, Inc.), the team has made another major advance in this field.

Building upon past advancements, a protocol has been developed whereby we are able to engineer genome variants of large DNA viruses by breaking the original genome up into smaller, overlapping pieces, that can then be independently modified, and then reassembled back into full-length virus genomes.

This allows for quick assembly of genome variants that can be used to understand the function of genes and gene combinations in viruses. Previous genetic systems for large DNA viruses, such as herpesviruses and poxviruses, required you to make one change at a time, making the new system significantly more efficient.

In our study, we used herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV), both members of the herpesvirus family. Herpesviruses can cause a range of diseases and symptoms, including cold sores, congenital birth defects, and cancer.

Fluorescence microscopy shows an HSV-1 genome engineered to express a fusion of viral protein VP16 and fluorescent protein Cerulean. Image by Peter Grzesik with assistance from The Johns Hopkins University Integrated Imaging Center.

Herpesviruses have extremely large genomes. HCMV is about 230,000 base pairs, the largest genome of any virus known to infect humans, and carries over 100 genes. Many of the functions of these genes are not yet known. We believe that our system will allow for a combinatorial approach to herpesvirus genetics that was not possible previously.

Rapid engineering of herpesviruses could also lead to new therapeutics and vaccines. For most herpesviruses, there are no effective vaccines. Improved genetics may allow us to rationally design and attenuate the virus, which would lead directly to vaccine strains.

Herpesviruses could be developed as delivery systems for gene therapy. Herpesviruses could also be developed to treat cancer as oncolytic viruses, which are viruses that attack cancer cells. An HSV-1-based oncolytic virus has already been approved by the FDA to treat melanoma and rapid engineering strategies could help generate oncolytic viruses to treat other cancers.

We believe this method to assemble and engineer virus genomes will be applicable to many different viruses and help expand our understanding of the basic biology of other viruses that are difficult to work with currently.

You can read more about this in the two original papers, and a just published commentary.

Genome-wide engineering of an infectious clone of herpes simplex virus type 1 using synthetic genomics assembly methods

Cloning, Assembly, and Modification of the Primary Human Cytomegalovirus Isolate Toledo by Yeast-Based Transformation-Associated Recombination

Commentary: Synthetic genome engineering gets infectious

Scientist Spotlight: Brett Pickett, Ph.D.

The son of a dentist, Brett Pickett grew up in Salt Lake City, Utah focused initially on a career in the family business (his siblings are hygienists and an oral surgeon). Brett believed from an early age that he would follow in his father’s footsteps. He enrolled in Brigham Young University committed to dental school. It was not until Brett’s zoology major was canceled that he became a student of microbiology, where he began researching antibiotic resistance genes in gut microbiota. Dental school was out. Brett received his B.S. in microbiology and continued his studies at the University of Alabama at Birmingham (UAB).

Brett Pickett

While working in UAB’s bacteria pathogenesis labs, Brett’s path would take another detour as he encountered West Nile, Hepatitis C, and Dengue viruses in his work. He also began to cultivate an interest in computers, technology, and statistics as it related to biological data. These experiences have led to him to his current field of research: viral bioinformatics.

In 2010, Brett moved to the University of Texas Southwestern Medical Center at Dallas to begin his postdoctoral research with Dr. Richard Scheuermann (presently the Director of JCVI La Jolla). Working with Richard, Brett began to shift his focus on how a virus behaves to examining how the human host is responding to being infected. While at UT Southwestern, Brett worked with Richard and his team to identify and develop new statistical, analysis, and visualization tools for the National Institutes of Health (NIH)-funded Viral Pathogen Resource Bioinformatics Database (ViPR). In 2012, Brett moved his family to La Jolla to be a part of JCVI’s informatics team. During this time, his work focused on enhancing the Virus Pathogen Resource and Influenza Research Database bioinformatics resource centers.

Brett stepped away from JCVI for a brief period to work at Thomson Reuters. There he analyzed “-omics” data with pathway analysis and network-building tools, together with drugs and protein target information to better understand viral infection, differences between pathogenic and commensal bacteria, oncology, and other therapeutic areas. This experience allowed him to gain a better understanding of human genetics, disease profiling, and biomarker identification before returning to research at JCVI in 2016.

At JCVI, Brett continues to work on cutting-edge science. He appreciates “the access to collaborators to solve big problems,” and Brett’s efforts are addressing the world’s biggest health challenges. He recently received funding from the US Agency for International Development (USAID) to develop a method for differentiating antibodies against Zika and other closely-related viruses in human patients.

Brett lives in San Diego with his wife and five children. When he is not in the lab, Brett enjoys golf, waterskiing, playing the piano, and visiting the beach with his family. His children, ranging in ages from 1-11, want to be scientists or doctors when they grow up. While there may be no dentists in this generation either, it is clear Brett’s children will have inspirational and accomplished footsteps in which to follow.