Posts tagged zika

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.

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!

Ongoing Zika virus work at JCVI

The rapidly developing Zika virus (ZIKV) outbreak has research groups, government agencies, and industry 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 two areas of ongoing ZIKV related work at JCVI.

Zika virus

This is a digitally-colorized transmission electron micrograph (TEM) of Zika virus, which is a member of the family Flaviviridae. Virus particles, here colored red, are 40 nm in diameter, with an outer envelope, and an inner dense core. Image credit: CDC/ Cynthia Goldsmith

JCVI/BEI Resources/NIAID: 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. 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. A list of the ZIKV isolates sequenced by JCVI are found here: https://www.beiresources.org/Organism/118/Zika-virus.aspx

JCVI/Sanofi-Pasteur/NIAID: 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). To distinguish between ZIKV and other viral diseases, we are developing a highly sensitive and specific ZIKV diagnostic assay. After confirming ZIKV positive samples, JCVI will perform whole genome sequencing and sequence analysis to understand the evolution of the virus over time and geographical location. We hope that results from this collaborative work will significantly increase our understanding of the origins of the ZIKV outbreak in the Americas and lay the groundwork for future collaborations with NIAID and Sanofi.