Posts in category Genomic Medicine

Research Impact: Accelerating Efforts to Contain and Prevent the Zika Virus (ZIKV)

The rapidly developing Zika virus (ZIKV) outbreak has research groups, government agencies, and industry is all striving to develop a response plan to contain and ultimately prevent ZIKV spread. Currently JCVI is working with both private and public sector funders to sequence and analyze historical and current ZIKV strains. Work at JCVI is geared toward developing sensitive ZIKV diagnostics, significantly increasing the number of ZIKV genomic sequences available, and performing cutting-edge analysis on current and future sequence data.  We expect these efforts to guide the rational design of ZIKV antivirals and vaccines to treat and prevent ZIKV-induced disease.   Here we highlight areas of ongoing ZIKV related work at JCVI.  In each area, additional funding would accelerate our efforts to understand and ultimately control ZIKV infection in the human population.

ZIKV

As of October 12, 2016 the Centers for Disease Control and Prevention reported 3,936 cases of ZIKV infection, with two Florida cities identified as the Ground Zero for local transmission.

ZIKV sequencing efforts at JCVI: 

  • JCVI, through an existing NIH funded grant, is working with the Biodefense and Emerging Infections Research Resources Repository (BEI Resources) to provide high quality sequence data for publically available ZIKV strains. These strains represent a collection of ZIKV isolates, ranging from the initial 1947 isolate from Uganda to 2015 isolates from Puerto Rico, Colombia, and Panama, Mexico, and Honduras. JCVI is providing the gold standard annotated reference sequence for all strains available from BEI and will continue this effort as BEI obtains additional ZIKV isolates.
  • Shortly after the recent Zika virus outbreak emerged in eastern Brazil, Dr. Richard Scheuermann and his bioinformatics team at JCVI collaborated with software engineers at Northrop Grumman to develop a custom Zika website portal to provide genomic sequence and other data about Zika virus through the public Virus Pathogen Resource (ViPR). As of September 2016, the ViPR Zika portal contains 389 genomic and 2399 protein sequences representing the three major Zika lineages – East African, West African and Asian. To support comparative genomics analysis to investigate the evolution of virulence in the newly emerging outbreak isolates, Scheuermann’s group developed an algorithm for predicting the proteolytic cleavage sites that generate Zika mature peptides, and applied this method to produce a comprehensive record of all predicted mature peptides for all Zika genomic sequence in the ViPR database.
  • JCVI is currently working with collaborators in Colombia and Nicaragua to collect sera from patients suspected to harbor ZIKV and to sequence the viral genome from these patients.
  • JCVI was recently awarded NIH supplemental funding to work with Sanofi-Pasteur to screen and sequence human samples suspected to be positive for ZIKV. The majority of samples, provided by Sanofi, are from children and adolescents from the Americas and the South Pacific where mosquito transmitted viruses are common. Over the upcoming year, JCVI anticipates screening both retrospective and prospective human serum samples for ZIKV, with the assumption that many of these samples are from individuals infected with other viral diseases (e.g. Dengue Virus).

Toward the development of a rapid ZIKV diagnostic:

  • Brett Pickett recently received funding from the US Agency for International Development (USAID) to develop a method for detecting antibodies against Zika virus in human patients. A bioinformatics analysis performed previously at JCVI uncovered regions of Flavivirus proteins that differentiate between 10 species of viruses—including Zika. Custom peptide arrays will be constructed to identify immunodominant epitopes in human serum, which we will then optimize as an ELISA-based diagnostic for use in developing countries.
  • To distinguish between ZIKV and other viral diseases, we are developing a highly sensitive and specific ZIKV diagnostic PCR assay.
  • Our assay is sensitive, and we have demonstrated the ability for the assay to identify ZIKV from diverse geographical regions. Future work seeks to move this technology from the laboratory to the field.

Next generation vaccine technology at JCVI can be applied to ZIKV:

  • JCVI has previously coupled synthetic biology for the rapid generation of an Influenza vaccine.
  • Currently, JCVI is using both synthetic biology and vaccinology to develop a universal vaccine for the common cold in partnership with Synthetic Genomics (A company founded by Dr. Venter) and private funders
  • The established vaccine technology at JCVI and our ability to rapidly identify and sequence ZIKV would allow the institute to pursue novel ZIKV vaccine platforms.

Mosquito genomic sequencing:

  • JCVI is currently sequencing the genome of a mosquito that is known to harbor ZIKV and is present in the Americas.
  • Determining the genomic sequence of this mosquito will help research groups identify develop targeted approaches to impair ZIKV replication in the mosquito host.

Current efforts to combat Zika virus involve CLIA-approved methods to detect viral genetic material. In addition, there are multiple players currently developing a vaccine including GlaxoSmithKline, Sanofi, and Onovio Pharmaceuticals. Ensuring that any vaccine doesn’t cause any neurodevelopmental problems further complicates these efforts. Vector control departments around the United States are currently spraying to eradicate adult and larval mosquitoes. While these endeavors serve to prevent virus infection and spread through mosquitoes, they have negatively affected bee populations and organic crops—potentially increasing public acceptance of sterile GMO mosquitoes.

One of the key questions that arose as a result of the Zika outbreak in the western hemisphere is if the virus has mutated to become more virulent, causing more severe neurological pathology than previously circulating strains.  Comparative genomics analysis using sequences and analysis tools in ViPR has identified both nucleotide and amino acid substitutions in the outbreak lineage that warrant further investigation to determine if they are responsible for the apparent increased virulence of the new outbreak strain.  With the detection of mosquito-borne transmission in Puerto Rica and the continental US, there is now a critical need for more funding for further research into the genomic determinants of virulence and for accelerated development of targeted diagnostics, therapeutics and vaccines. Donate today!

Zoo in You: The Human Microbiome Exhibit Opens in San Diego

On January 28, over 250 scientists, philanthropists and other STEM community notables, including JCVI CEO Council Member Reena Horowitz, came out to support the San Diego premier of the Zoo in You: The Human Microbiome exhibit at the Reuben H. Fleet Science Center. The Zoo in You is a new 2,000 sq. ft. exhibit funded by a SEPA grant from NIH in partnership with JCVI. Through May 8, 2016 visitors to the display can learn about our constant microbial companions, where they live, how diverse they are, and in what ways scientists are realizing just how important they are to our personal health.

Dr. Karen Nelson

JCVI’s President, Karen Nelson, Ph.D., spoke about JCVI’s passion for STEM education and dedication to encouraging STEM growth in San Diego.

JCVI at Zoo in You Opening

JCVI staff and friends came out to support the event (from left to right): Hernan Lorenzi, Katie Collins, Karen Beeri, Amani Rushing, CEO Council Member Reena Horowitz, Nicole Deberg, Mark Adams.

Thanks to new, sophisticated technology and the cutting-edge research of the National Institutes of Health’s Human Microbiome Project, the world is just starting to discover what the microbes in each of us are up to and how they affect us.

JCVI is taking other steps to help the San Diego community learn about the importance of their microbiomes. In addition to the exhibit, JCVI scientist Karen Beeri led a class of 23 girls in activities about microbes and DNA sequencing at Fleet’s Saturday Science Club for Girls on February 13. The girls toured the Zoo in You exhibit, made DNA bracelets, and used RNA decoders to decode the secret messages found in our amino acids.

Zoo in You: The Human Microbiome will be on display at Fleet until May 8, 2016. Check it out!

For more information about JCVI’s education initiatives, please contact Education Manager Amani Rushing at arushing@jcvi.org.

June Grant Update

Congratulations to our JCVI Principal Investigators for the several successful grants that were awarded or that we received notification of in the month of June. All of the following PIs received official confirmation of awards to be made to them. Christopher Dupont, John Glass, Granger Sutton, Daniel Gibson, Charles Merryman, Rembert Pieper, Richard Scheuermann, Christopher Town, Reed Shabman, Orianna Bretschger, Sanjay Vashee and Sarah Highlander to the sum of $6,365,099. The topics of these awards ranged from synthetic approaches to studying the human microbiome, vaccine development, protein modeling, studies on tuberculosis strain diversity, and immune profiling.

Of notable mention are the awards to be made to Sanjay Vashee $1,879,282 from the NSF (BREAD supplement that will allow for an extension of the current program focused on developing a synthetic vaccine for Bovine pleuropneumonia), Reed Shabman from DHS ($1,135,654; The development and validation of sequence subtraction databases to improve virus discovery through next generation sequencing – special acknowledgement to Tim Stockwell and Derek Harkins for their contributions to this proposal), and to Chris Town from NSF ($883,704; Federated Plant Data Base Initiative for Legumes).

A sincere Congratulations to the team.

Johns Hopkins Announces Inaugural Recipient of Hamilton Smith Award for Innovative Research

JCVI’s Hamilton O. Smith, MD has been recognized by Johns Hopkins University with a research award in his honor. The inaugural recipient of the award is Jie Xiao, an associate professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine. Dr. Smith was awarded the Nobel Prize in 1978 for his discovery of restriction enzymes, work he conducted while he was a young faculty member at Johns Hopkins.

Zoo in You Exhibit Now Open

Did you know trillions of microbes make their homes inside your body? In fact, these microorganisms outnumber our human cells 10 to 1, “colonize” us right from birth, and are so interwoven into our existence that without each other, none of us would survive! Thanks to new sophisticated technology and the cutting-edge research of the Human Microbiome Project, we are just starting to discover what these microbes are up to and how they affect us. And now in Zoo in You: The Human Microbiome, a new 2,000 square foot bilingual traveling exhibit created in partnership between JCVI and the Oregon Museum of Science and Industry (OMSI), and funded by a SEPA grant from the NIH, visitors can now explore this fascinating and complex world inside us that is our microbiome—a dynamic, adaptable, and delicately balanced ecosystem like any other found in nature.

A few of the Zoo in You components including “Weather Reports” and “Microbes in the Family”

A few of the Zoo in You components including “Weather Reports” and “Microbes in the Family”

The exhibition features 15 interactive, free floating hands on components that are designed to focus on three overarching topic areas to educate and inform visitors on the concept that our bodies are complex ecosystems that we are just starting to understand and explore.  Through these exhibit components museum goers will “meet the microbes” to learn about the organisms which live on and inside us from the moment we are born, to understanding the importance of the dynamic and delicately balanced human microbiome in “balanced ecosystems”, and lastly visitors will “explore the microbiome” to learn the importance of scientific research to increase our understanding of human health.

Zoo In You introduction component “Meet the Microbes”

Zoo In You introduction component “Meet the Microbes”

There are numerous interactive, hands on activities for visitors.  Such activities include “Weather Reports” where guests will have the opportunity to interact with green screen technology to give a weather report on the climate conditions of your nose, gut or skin.  They also will be able to build a DNA Puzzle where they race against the clock to assemble a DNA strand and participate in a hand washing contest.   Participants can challenge each other in exhibit components such as “Microbes in Balance”, a large touch screen video game to see if they can keep their “health-o-meter” in balance and in “Microbe Mirror” a motion sensing activity where visitors come face to face with their full body reflection and control the changes in their microbiome as they react to everyday occurrences.  Throughout the exhibit components feature contributions by JCVI Scientists Dr. Karen E. Nelson, Dr. Hernan A. Lorenzi, and Dr. Ramana Madupu including “Stories & Choices” an activity where visitors listen to the scientist interviews and make choices based on various fun questions which relate to microbiome research.

The Zoo in You exhibit is now on display at the Oregon Museum of Science and Industry (OMSI) in Portland, OR through July 2015, it will then travel to Science Works Hands-On Museum in Ashland, OR October through December 2015.  It will begin its national tour at the Reuben H. Fleet Science Center in San Diego, CA in partnership with JCVI.

Guest Speakers Marlo Gottfurcht Longstreet and Dean Ornish Inspire Guests at JCVI‘s “Life at the Speed of Light” Gala

On October 18, J. Craig Venter Institute (JCVI) hosted our “Life at the Speed of Light” black tie gala featuring special guests Dean Ornish, MD, and Marlo Gottfurcht Longstreet. JCVI welcomed 200 community leaders, sponsors and supporters including Representative Scott Peters, Susan Taylor, Reena Horowitz, Linda Chester, Jack McGrory, Jessie Knight, Jr., Joye Blount, Wendy Walker, Randy Woods, Andrew and Erna Viterbi, Mary Ann Beyster, and JCVI Board Member Bill Walton and wife Lori.

Guests experienced our science first hand through various displays and had the opportunity to interact with many JCVI scientists to learn how advances in genomics are impacting our health and environment.

microbiome station

JCVI Scientists Manny Torralba and Stephanie Mounaud welcomed guests with a brief introduction to the palm microbiome by taking swabs and sharing aggregate population results midevening.

Following welcome remarks by J. Craig Venter, Ph.D., Founder & CEO of JCVI, Marlo Gottfurcht Longstreet shared her son Tanner’s battle with a Giloblastoma Brain Tumor. It is understood that the tumor developed as a result of a mutation in the TP53 tumor suppressor gene. Sadly, Tanner Jay Longstreet passed away in 2013 at the age of 11.

Marlo Gottfurcht Longstreet sharing her personal story about her son Tanner and ongoing work at the Tanner Project.

Marlo Gottfurcht Longstreet sharing her personal story about her son Tanner and ongoing work at the Tanner Project.

Personal tragedy turned mission for Marlo as she set out to do everything she could to better understand what afflicted Tanner, which gave rise to the Tanner Project at JCVI. Led by Nicholas Schork, Ph.D., the Tanner Project is what is referred to as an “N of 1” project – a single patient case study. Rather than go in for yearly checkups, the patient in the study is monitored daily so that any evidence of cancer can be detected at onset. The goal is to keep the study patient at what is referred to as stage 0. By closely monitoring the condition in this “N of 1” study, its application can be applied more broadly in personalized medicine – “N of 1 for everyone.”

Dr. Ornish discussed advances in personalized medicine and how simple behavioral changes can greatly affect patient outcomes. He addressed ideas presented in his most recent book, The Spectrum, suggesting diet and exercise are not all or nothing propositions. If today wasn’t a great food day, there is no reason tomorrow can’t be. This kind of thinking can greatly improve longevity and quality of life.

Dean Ornish speaking to gala attendees on advances in medicine.

Nobel Laureate Hamilton Smith (right) walks gala attendees through JCVI advances.

Rangers and the Re-Arrangers

The evening was rounded out with a delectable dinner, dancing, and gypsy jazz music by Seattle’s Rangers and the Re-Arrangers.

JCVI is grateful to its event sponsors – CapitalOne Bank, BioMed Realty, Synthetic Genomics, Inc., Human Longevity, Inc., Thermo Fisher Scientific, Gunderson Dettmer, ZGF, and Egon Zehnder – for their support. Thank you as well to our DNA gift bag sponsors: Way Better Snacks, GoodBelly, Kowalski Communications, La Jolla Playhouse, Lean & Green Café, and Travel Set Go.

JCVI remains committed to tackling today’s pressing medical and environmental concerns, and we continue to rely on your generosity to achieve our goals. For more information on funding needs and opportunities, please contact Katie Collins as kcollins@jcvi.org.

Study Signals Bat Flu Unlikely to Jump to Humans

Bats species harbor a large number of viruses that cause human disease.  So, when the first influenza sequences from Guatemalan little yellow-shouldered bats were uncovered in 2009, the question arose of whether bat influenza viruses pose a threat to human health.  A collaborative project between JCVI and Kansas State University was recently published in PLoS Pathogens to address this question.

H1N1 influenza virus particles

Image Credit: National Institute of Allergy and Infectious Diseases (NIAID)

The approach employed cutting-edge synthetic biology approaches and demonstrated that, while the sequences of the bat influenza virus of the subtype H17N10 are viable, they are unable to infect human cells. Additional experiments clearly indicated that these bat virus sequences are not able to reassort with other influenza A and B viruses known to infect humans. Therefore, the potential for a pandemic bat influenza entering the human population is extremely unlikely.

David Wentworth, the former Director of Viral Programs at JCVI, was the lead investigator for this study.  Additional authors from JCVI include Tim Stockwell, Wei Wang, Xudong Lin, Bin Zhou (now at NYU), and Reed Shabman.

For additional information see the press release.

H3Africa Update

The National Institutes of Health (NIH) and the UK-based Wellcome Trust, in partnership with the African Society of Human Genetics, developed a program to foster genomic and epidemiological research in African scientific institutions. The laboratory and computational infrastructure available to most scientists on the African continent is currently insufficient to keep up with the rapid developments in DNA sequencing technologies and the need to use advanced computationally intensive methods to analyze this data.

Through the H3Africa Consortium, a partnership between NIH and Wellcome Trust, funding has become available to support knowledge development and implementation of genomics-centered research in several African academic institutions. The first scientific paper to come from this effort, Enabeling the Genomic Revolution in Africa, was published in the journal Science in June 2014.

H3Africa Efforts at J. Craig Venter Institute (JCVI)

One of the main initiatives of H3Africa is to foster scientific exchange between US-based partners and their African-based consortium members. JCVI is involved in a number of such partnerships through training and research collaborations.

Tuberculosis Research with Addis Ababa University

Addis Ababa University is the only Ethiopian institution to receive a primary award from NIH under H3Africa. It is based on a collaboration with JCVI. Professor Gobena Ameni of Addis Ababa University and Dr. Rembert Pieper of JCVI developed a proposal on Systems Biology for Molecular Analysis of Tuberculosis in Ethiopia which was initiated earlier this year. The research focuses on genomic variability in M. tuberculosis strains in Ethiopian pastoralist societies and also has an oral microbiome and proteomic biomarker discovery component.

Bioinformatics Training for African Scientists

As part of H3Africa, JCVI is leveraging its recent GCID award, where appropriate, for training of African Scientists. As part of this effort Dr. Andrey Tovchigrechko  taught microbiome analysis to graduate students in Ibadan, Nigeria. The workshop was organized by the local H3Africa Bioinformatics Network node. The workshop took place in July, 2014 and comprised of students from Nigeria and other West and Central African countries.

Symposium presenters.

Symposium presenters.

Workshop student participants.

Workshop participants.

The workshop was held at IITA.

The workshop was held at IITA.

During the three day workshop, Dr. Tovchigrechko taught the students launching and controlling computing instances on Amazon cloud, the basics of Python and R programming, MG-RAST Web interface, MG-RAST R package matR and JCVI-developed R code MGSAT. MG-RAST tutorials were provided by one of its developers Andreas Wilke (ANL).

Dr. Tovchigrechko also gave a talk, along with a dozen other speakers, at a one-day symposium at the University of Ibadan that preceded the workshop and included approximately 200 participants. Special thanks go to Nash Oyekanmi, the organizer and manager of the whole event, for his relentless efforts.

Collaborations with University of Cape Town

Also as part of the H3Africa Consortium, Dr. William Nierman from JCVI and Dr. Mark Nicol from the University of Cape Town, South Africa are in collaboration to study the nasopharyngeal microbiome and respiratory disease in African children. Dr. Nierman’s group has conducted a month long in house microbiome training workshop with students from Dr. Nicol’s group.

The focus of the training was to teach students JCVI’s complete microbiome pipeline (including sample preparation, sequencing generation, and final association analysis). The aim of the training collaboration is to ensure that this complete pipeline can be performed at the University of Cape Town, to help build independent and sustainable capacity in this field within South Africa.

 

J. Craig Venter at Recent Google Zeitgeist Conference [VIDEO]

Dr. J. Craig Venter recently spoke at a Google Zeitgeist conference in Arizona where he spoke on advances in genomics, synthetic biology, and DNA as the software of life.

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

Greenland

Greenland