Posts in category Infectious Disease

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Meet Richard Scheuermann, Ph.D., JCVI’s Director of Bioinformatics

Richard H. Scheuermann, Ph.D., who joined JCVI in 2012 from the University of Texas Southwestern as the Director of Bioinformatics, is an accomplished researcher and educator. He and his team apply their deep knowledge in molecular immunology and infectious disease to develop novel computational data mining methods and knowledge representation approaches.

Richard Scheuermann

Richard Scheuermann, Ph.D., JCVI’s Director of Bioinformatics

From an early age, Richard was very interested in science and the living world around him.  He was a curious child who loved to explore the ponds and fields in his hometown of Warwick, New York.   This rural community in upstate New York is covered with dairy farms and apple orchards.  He demonstrated an early aptitude for math and science and was fortunate to have talented high school teachers who recognized his potential.   Although neither of Richard’s parents were college educated, they encouraged his academic pursuits.  When Richard and his father met the high school guidance counselor, Richard told of his intention to attend the Massachusetts Institute of Technology (MIT).  The response from the counselor was a resounding, “There is no way you’ll ever get in.” Richard applied to MIT (and only MIT) anyway, and was accepted by early decision.

At MIT Richard intended to pursue a career in chemical engineering (CE) but to his surprise, he found that he loathed the CE classes.  While trying to identify a new study path, Richard took a biochemistry class to fulfill a CE requirement.  This class would change Richard’s career path.  While at MIT, Richard worked in the lab of Annamaria Torrianni-Gorini, Ph.D. and received first hand experience in conducting scientific research.  He was inspired by his peers and professors and had found his calling. During this time he also had the privilege to study with Salvador Luria, Ph.D., David Baltimore, Ph.D., David Botstein, Ph.D., and Phil Sharp, Ph.D., all luminaries in their fields. Richard received a B.S. in Life Sciences from MIT in 1981.

Richard went on to complete his Ph.D. in Molecular Biology at the University of California, Berkeley.  After completing his doctoral research on bacterial replication fidelity at U.C. Berkeley with Hatch Echols, Ph.D., Richard was offered his own research lab in Europe.  He accepted an independent research position at the Basel Institute for Immunology in Switzerland, where he identified the CDP protein as a critical regulator of immunoglobin gene expression and the role of nuclear matrix attachment in transcription regulation.

Although Richard had trained as a molecular biologist, in 1992 he was recruited into the Department of Pathology at the University of Texas Southwestern Medical Center (U.T. Southwestern) in Dallas.  Apprehensive at the beginning to find himself in a clinical department, as he had at every previous crossroads, Richard quickly embraced the opportunity before him.  He changed his research focus to disease and disease pathogenesis, and he rose to the rank of Professor with tenure. Richard established a robust research program at U.T. Southwestern investigating signal transduction pathways that regulate normal lymphocyte development and function and that induce cell cycle arrest, apoptosis and dormancy in lymphomas. This important work was supported through numerous research grants from the National Institutes of Health, the American Cancer Society, the Texas Higher Education Coordinating Board, and other granting agencies.  In the Pathology Department, he also worked on the development and validation of novel diagnostic methods for viruses that mediate chronic infectious disease and for chromosomal translocations that drive leukemia and lymphoma development.

Half way through his U.T. Southwestern career, Richard had found life in the wet lab less and less fulfilling.  Through his involvement in several high-throughput research projects Richard realized that it was becoming relatively easy to generate lots of data but more difficult to analyze the information.  And so he decided to take a sabbatical year at the San Diego Supercomputer Center to immerse himself into the emerging field of bioinformatics. After his time in San Diego, Richard was drawn into the bioinformatics discipline, and he redirected his career with three research and development proposals funded in rapid succession.

Richard established a very successful bioinformatics program at U.T. Southwestern; however, he was searching for new opportunities to expand on his success.  In 2012, the invitation to join JCVI, a “bleeding-edge research institution that valued informatics” could not be ignored.

As the Director of Bioinformatics at JCVI, Richard leads a multi-disciplinary team of computational biologists. Richard and his team continue to develop novel computational methods to accelerate data mining and statistical analysis. These methods have been made available to the research community through several public database and analysis resources, including the Influenza Research Database (IRD; www.fludb.org), the Virus Pathogen Resource (ViPR; www.viprbrc.org) and the Immunology Database and Analysis Portal (ImmPort; www.immport.org) supported by the National Institutes of Health. His current research is focused on human pathogenic viruses—how they spread and cause disease.  He is a part of the elite community that responds to virus outbreaks, such as the recent Ebola and Enterovirus D68 occurrences.  This “real time sorting out” of emerging infectious diseases keeps his still curious New York state of mind engaged and excited about his work.

In his spare time Richard enjoys swimming, soccer and skiing and spending time with his wife, Nancy, and sons, Alex and Derek.  Over the past thirteen years, he has studied martial arts, earning his first-degree black belt.   As it was in the outskirts of Warwick, Richard continues to explore his new San Diego environment, and is rapidly becoming an avid sailor.

Richard’s commitment and determination to a path, whether on the high seas or in the lab, are unrivaled.  Like him, his peers at JCVI are excited to see where his research will take us next.

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.

2015 Advanced Genomics, Metagenomics, and Bioinformatics Workshop Wrap-up

I was lucky enough to help set up and plan a workshop covering genomics, metagenomics, proteomics and bioinformatics at the University of the West Indies campus in St. Augustine, Trinidad & Tobago on February 19th and 20th. The workshop was sponsored by the National Institute of Allergy and Infectious Diseases through the Genomic Center for Infectious Diseases cooperative agreement. UWI was a co-sponsor and a gracious host. Participants included 60 individuals from Trinidad, England, Guyana and Barbados. On-line participants were from all over the world including Gambia, Ethiopia, Kenya, India, USA, and the Caribbean.


file-pdf Workshop Slides (PDF – 29MB)


The team of presenters from the JCVI included Karen Nelson, Bill Nierman, Andrey Tovchigrechko, Rembert Pieper, and Shibu Yooseph.  Presenters from UWI included Drs. Christine Carrington and Adesh Ramsubhag.

Karen opened the workshop with a welcome message and overview. She has been a driving force behind the growing relationship between UWI and JCVI. Bill delivered very interesting talks on the history of research on the human microbiome and currently emerging infectious diseases. Rembert handled a presentation and tutorial on proteomic analysis strategies, which was a big hit. If time was not a factor, the question and answer period could have lasted longer than his talk. Finally, Andrey and Shibu presented and gave lessons on statistics, UNIX, and bioinformatics analyses for genomics, metagenomics, and microbiome work.

Dr. Carrington’s presentation on infectious diseases in Trinidad focused on Dengue Fever and Chickungunya, and dovetailed quite nicely with Bill’s presentation on emerging infectious diseases.

Dr. Ramsubhag described the results of his work examining the bacterial diversity of the Nariva Swamp in Trinidad, which uncovered many unique bacterial strains. Perhaps the most important portion of his talk described how important this type of workshop/collaboration is for UWI. Lessons from subject matter experts are invaluable to the undergraduate, graduate and faculty members that attended the workshop as students. In addition, Dr. Ramsuhbag described how a relationship that started through a workshop has given UWI access to cutting edge technologies and data analysis strategies that would be otherwise unavailable without the collaboration with the JCVI.

The students that attended the workshop were all very enthusiastic and eager to learn. They seemingly hung on every word from the presenters, and paid very close attention during the presentations and hands on informatics sessions. A few attendees even asked us to make the lunch break shorter so that the workshop time could be lengthened…but we needed that time to break down the video equipment, haul it to another building and set it up for the afternoon classes. It was a pleasure to help make this learning experience possible for the workshop students!

The workshop was the second time that staff from the JCVI have presented at the St. Augustine Campus of UWI. Tim Stockwell held an 8 hour workshop focused on viruses in 2013.  We look forward to working together in the future.

Special thanks to Tim Stayeas for handling all of the technology associated with on-line broadcasts of the meeting.

Watch all four training sessions below:

Day 1, AM Session

Day 1, PM Session

Day 2, AM Session

Day 2, PM Session

Impact: Ebola Research Efforts at JCVI

We have all read the stories with concern about the rapid spread of Ebola virus disease (EVD) in Africa. Now, with the first diagnosis of the virus in the United States, it is clear this virus is not under control. If not contained, Ebola poses a significant threat to the African continent and beyond. JCVI is on the front lines of working to better understand this infectious agent. Dr. Reed Shabman, a member of JCVI’s infectious disease team, is seeking to understand why Ebola and Marburg viruses (both are filoviruses) infections result in such severe human disease.

Ebola virus

Produced by the National Institute of Allergy and Infectious Diseases (NIAID), under a magnification of 25,000X, this digitally-colorized scanning electron micrograph (SEM) depicts numerous filamentous Ebola virus particles (red) budding from a chronically-infected VERO E6 cell (blue). Image credit: NIAID

During his time as a postdoc at the Icahn School of Medicine at Mount Sinai in New York, Reed helped to develop research platforms designed to understand how Ebola virus mediates its replication, gene expression and evades the immune system. The innovative approaches used at JCVI do not require high level containment facilities and through established collaborations with Biosafety level-4 (BSL-4) labs his group is able to confirm their results in the context of actual Ebola infection.

Some of the ongoing collaborative projects in the group include:

  • Determining how Ebola virus evades the host immune system, specifically the innate immune response.
  • Employing sequencing platforms to identify previously undescribed aspects of Ebola and Marburg virus RNAs.
  • Developing reporter systems to understand how the untranslated regions (UTRs) of Ebola and Marburg virus control their protein production.

This important research seeks to enhance the scientific community’s understanding of Ebola and Marburg virus biology which will aid in our ability to rationally design ways to combat these deadly viruses.

Ebola Background

Ebola has entered the human population before, with the first documented cases occurring in 1976 in areas that are now South Sudan and the Democratic Republic of Congo. Since 1976, there have been approximately 20 outbreaks in central Africa resulting in just over 2300 confirmed cases of Ebola virus disease (EVD).

One unusual aspect of the current Ebola outbreak is that instead of central Africa, this outbreak is occurring in west Africa. Initial cases were reported in February in Guinea. Shortly after these initial reports, EVD spread into Liberia followed by cases in Sierra Leeone and Nigeria. While efforts to control the virus in Nigeria appear to be successful, the number of cases since the first reported case now totals approximately 8000 with almost 4000 fatalities. The numbers from this single outbreak are larger than all other previous outbreaks combined.

Ebola virus was identified almost 40 years ago; however, there are still no approved vaccines or antiviral approaches beyond supportive care. There are promising therapies and vaccines on the horizon, but a fundamental understanding of how the virus interacts with human host is critical to advance the progress of treating the deadly disease.

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.

 

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 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.

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.

‘Twas the night before Christmas

‘Twas the night before Christmas, when all through the building
All our creatures were stirring, even our mold;
The dishes were placed in the incubator with prayer,
In hopes that pure growth soon would be there;

The scientists were nestled all close to their screens instead
While swirls of DNA danced in their heads;

My coworker in her labcoat, and I with my pipettor,
Had just settled down for a long overnighter,

When out in the lab there arose such a clatter,
I sprang from my microscope to see what was the matter.
Away to the incubator I flew like a flash,
Tore open the doors then saw what was trash.

When, what to my tired red eyes should appear,
But a bunch of contaminated plates, there goes my career.

Santa Hat - Ho Ho Ho

Brim and ball: Neosartorya fischeri; Hat: Penicillium marneffei; Ho,Ho,Ho: Aspergillus flavus. Image Credit: Stephanie Mounaud / J. Craig Venter Institute.

Last year, still in an isolated fungal room placed far away from others, I made an attempt at this one, but my stocks were contaminated. Something all fungal folks know something about. (Aspergillus is just EVERYWHERE). So with a little luck (let’s face it, with complete luck) I was able to clean things up and told the fungus to be on its best behavior. However, N. fischeri still did not want to play nice with the P. marneffei…so they remained slightly separated.

Fungal Christmas Tree

Star: Talaromyces stipitatus; Tree: Aspergillus nidulans Ornaments: Penicillium marneffei; Trunk: Aspergillus terreus. Image Credit: Stephanie Mounaud / J. Craig Venter Institute.

I hope everyone enjoys my creation, although the credit goes to my jolly ole fungus for being so wonderfully diverse and satisfying my slightly nerdy creative side.

Fungalman

Hat, Eyes, Mouth, Buttons: Aspergillus niger; Arms: Aspergillus nidulans; Nose: Aspergillus terreus with Penicillium marneffei; Body: Neosartorya fischeri. Image Credit: Stephanie Mounaud / J. Craig Venter Institute.

Let us all show the world the true side of fungus and all its amazing potential. Because we all know they can do more than just sit there and look pretty.