Coronavirus: structure-function

The outbreak of a novel coronavirus, COVID-19, has now become a pandemic threat that has been declared a public health emergency of international concern. Although it is hard to predict the future expansion of the COVID-19 pandemic, disease experts agree that it is still going to spread in most places. For an updated live tracking of COVID-19 cases, check out trackcorona.live For a detailed updated overview of the features, evaluation and treatment of COVID-19, you can check out the NCBI page here.

Transmission electron microscope of SARS-CoV-2

Figure 1: This transmission electron microscope image shows SARS-CoV-2, the virus that causes COVID-19—isolated from a patient in the U.S. The spikes on the outer edge of the virus particles give coronaviruses their name, crown-like. Credit: NIAID-RML

There is certainly a lot of similarity between the current COVID-19 virus and the SARS-CoV virus responsible for the 2003 pandemic. They both belong to the Coronavirideae family and have very similar structures and virus replication cycles. All coronaviruses are positive-stranded RNA viruses with a crown-like shape due to the spike glycoproteins on the surface (Figure 1; coronam is the Latin term for crown). However, when we look in more detail at a structural comparison at the biochemical level, we can see some possibly important differences between COVID-19 and the 2003 SARS-CoV virus.

One essential component of the virus infection is the spike protein. These spike proteins are on the surface of coronaviruses and attach the virus to the human cells during infection. After attachment, it fuses with the host cell membrane and releases its own genome into the host cell. Because the spike protein is on the surface and is essential for infection of the host, it is a key target for potential vaccines and diagnostics. Figure 2 shows a structural overlay of the spike protein from COVID-19 (yellow) and SARS from 2003 in blue. Both of these bind the human angiotensin-converting enzyme 2 (ACE2) receptor, but have distinct differences in their affinity for the receptor. The COVID-19 S protein binds ACE2 with higher affinity than does SARS-CoV, which likely contributes to its higher infection rate.

SARS-COVID-19 SpikeOverlay

Figure 2: Structural overlay of the spike protein S from COVID-19 (yellow) and SARS from 2003 (blue). The protein structures were obtained from PDB and rendered with Pymol by J. Kyndt. PDB Accession numbers: PDB6vsb and PDB6crz.

 

Another interesting comparison can be done by looking at the protease that cuts the long viral polypeptide into functional pieces (once it is inside the host cell). This protease also clips several proteins in the infected host cell and is certainly a target for therapeutics. There is a very high amino acid sequence identity (96%) between the COVID-19 coronavirus 3CL hydrolase (Mpro) and the SARS-CoV virus main protease. A structural overlay is shown in figure 3 with COVID-19 Mpro in green and SARS-CoV in red. There are 14 amino acid differences which are shown with their side chains in white.

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Figure 3: Structural overlay of the main protease MPro from COVID-19 (green) and from SARS (red). Amino acid differences are shown as stick models in white. A known inhibitor of MPro is shown in its binding site in blue. The protein structures were obtained from PDB and rendered with Pymol by J. Kyndt. PDB Accession numbers: PDB6lu7 and PDB1q2w.

Comparisons like these help us understand why this virus is more contagious, but less deadly than SARS, and can eventually give us a potential target for vaccines or therapeutics.

Test your 3D Stereo viewing skills of the coronavirus (Figure 4) and of the protease Mpro and spike protein S (Figures 5 and 6). Position your eyes about a foot away from the screen, stare at the middle of the image and slowly cross your eyes. A third image will appear in the middle in 3D! Keep trying and move closer or further away from the image and eventually you’ll get it.

Stereoscopic Sars-cov-2 virus

Figure 4: Stereoscopic image of a model of the complete SARS-Cov-2 (COVID-19) virus. Just stare at the red pixel in the center, and allow yourself to go cross-eyed!   Stereo rendering by J. Farnen.

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Figure 5: Stereo view of MPro overlay from COVID-19 (green) and SARS (red). Image by J. Kyndt.

SARS SpikeOverlay Stereo

Figure 6: Stereo view of the spike viral protein from COVID-19 (yellow) and SARS (blue). Image by J. Kyndt.

A lot of research is currently ongoing, with many new research and funding opportunities on this topic. For example, the Bill and Melinda Gates foundation recently launched an initiative to speed up the development and access to therapies against COVID-19, this includes a $100 million dollar commitment to the COVID-19 response.

Although there are many scary and worrisome aspects of this current pandemic, in the long run it will eventually lead to a better understanding and valuable scientific lessons to be learned. This is certainly not the last pandemic humankind will experience, afterall we live in a microbial world, but understanding the biochemistry and molecular biology that is underneath these outbreaks might help us to react more efficiently and possibly prevent the fast spread of future viral outbreaks.

Spike COVID-19 spacefill

Space fill model of the COVID-19 Spike protein. Chains A, B and C are colored pink, green and cyan. NAG (N-Acetyl-D-Glucosamine) ligands are colored yellow.                                                            PDB 6vsb rendered in Pymol by J Kyndt.

 

Story written by Margie McCandless

What is going on in the area of campus just to the north of the Learning Center? You might have noticed that space was cleared, large landscaping pavers installed, and little plants appeared everywhere on the hill. This is actually a garden of native Nebraska plants and just the beginning of a three year innovative project, the Bellevue University Sustainability Learning Lab.

IMG_2982Partially funded by a $200,000 grant from the Nebraska Environmental Trust, the lab will be a bonus to both students, especially biology and sustainability management students, and the community. Commenting on the award, Dr. Dennis Joslin, Executive Director of the Council of Independent Nebraska Colleges Foundation, sums it up by saying, “The Sustainability Learning Lab has tremendous potential to benefit the State of Nebraska by raising awareness and educating future generations of students and citizens about how to conserve, enhance and restore natural environments.”

Sustainability is a word that is tossed about a lot these days, but what exactly does that mean? A commonly quoted definition from the UN World Commission on Environment and Development says, “Sustainable development is development that meets the needs of the present without compromising the ability of future generations to meet their own needs.” It revolves around three fundamental pillars, people, planet, and profit. In a nutshell, that means that it is beneficial to the community, good for the environment, and makes economic sense. Dr. John Kyndt, Associate Professor of Microbiology and Director of Sustainability, notes that our energy resources are finite and some day will be used up if we don’t start finding ways to conserve them. He sees the lab as being a good way to have “science on display” and to involve the community by inviting them to enjoy the space and even plant their own native plants.

When finished, the Lab will be a 7000 square foot indoor outdoor area consisting of a greenhouse, algae pond, wind and solar energy generating stations, and the native plants garden. The lab will give students a unique hands-on opportunity to study renewable energy. Specifically, the new lab will allow students to create biofuels out of pond algae. They will be studying types of algae and best methods to efficiently create biofuel. In the greenhouse, students will study and work with hydroponic methods of plant production, a method of growing plants using mineral nutrient solutions in water rather than soil. This method provides higher yields, better quality crops, uses less water, and nearly eliminates disease, pests, and weeds.

IMG_2353Though it is a three year project, much progress will already be seen in the Spring of 2020 when the 1,600 square foot greenhouse is built. In the second phase, the 1200 square foot algae pond and the solar and wind generation stations will be installed. The third phase will see the construction of a 25-seat outdoor amphitheater classroom.  Though the NET grant provided the initial impetus, this will be matched by the university and its donors. Ground was broken in October and the lab will be officially completed in 2022 though much of it will be in use well before then.

For more information, see these news stories:

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For scientists, sequencing a genome is truly cause for celebration.

Which is exactly why Bellevue University Science Lab faculty and students gathered recently at a pizza party to mark an important Lab milestone – sequencing 50 genomes from all around the world.

According to Dr. John Kyndt, Associate Professor in the College of Science and Technology, sequencing a genome is an important step toward decoding an organism, which is the ultimate goal. As he describes it, that journey of understanding is serious business, to be sure, but it is also a fun process of discovery for both veteran scientists and the undergraduate microbiology students at Bellevue University.

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BU students enjoying the 50th Genome Pizza party

“Sequencing genomes is key to advancing science,” explains Dr. Kyndt. Every living organism includes genomes, which are composed of the organism’s DNA. And whether they belong to human DNA, bacteria, viruses or other simple forms of life, he adds, sequenced genomes provide a roadmap that help scientists find genes and better understand how the genes work together to direct an organism’s growth and development.

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Dr. Tyler Moore and BU Biology Alumni reunited at the 50th genome celebration.

As one of the most technologically advanced small labs in Nebraska, Bellevue University’s Science Lab allows students to get directly involved in genome sequencing projects. “Students are at the center of our open access, innovative environment” said Dr. Mary Dobransky, Dean of the College of Science and Technology. Ten genome sequences from organism samples have been published in academic journals and “more are on the way,” says Dr. Kyndt.

“With administration support – and some pizza – we are able to get amazing results in our student-driven research projects.” – Dr. John Kyndt, Assistant Professor, Bellevue University

Because of their important foundational role, scientists around the world study and sequence genomes. Perhaps the most high profile genome study is the Human Genome Project, a 13-year effort to identify all of the 20,000-plus genes in human DNA that was completed early, in 2003, largely due to technological automation.

Technology has accelerated Bellevue University’s efforts, too. Thanks to a partnership with Illumina, a global leader in Next Generation, or high-throughput, genomics, Bellevue University undergraduate students have learned how to use cutting-edge genomic sequencing software – all the way from how to extract DNA from a sample to how to run the samples through the Illumina MiniSeq system.

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Dr. John Kyndt and Louise McConnell (Illumina Executive Account Manager) discuss future student sequencing projects.

Amiera Rayyan, who completed her Bachelor of Science in Biology at Bellevue University in 2018, was among the first to use the MiniSeq system and as a result received lead author credit on two research papers published in academic journals. Sydney Robertson, another biology graduate who also has earned lead author credit on multiple published academic research papers, says, “The experience I had was more than just helpful in the classroom. I was able to collaborate with the professors and other institutions, really learning how to communicate effectively.”

As the success experienced by students like Amiera and Sydney and the genome sequencing continues in the University’s Science Lab, Dr. Kyndt says the impact – on science and on students – should never be underestimated. “It is very rare that undergraduates get published in a scientific, peer-reviewed journal, especially as the lead author,” he notes. “We are able to give students this opportunity because of our smaller class sizes, close professor involvement, and a deliberate focus to integrate more real-life research.”

50th Genome ShowStory written by Cris Hay-Merchant, Director of Strategic Communications at Bellevue University.

 

 

Illumina is a global leader in genomics and Next Generation sequencing. Illumina’s innovative sequencing and array technologies are fueling groundbreaking advancements in life science research, translational and consumer genomics, and molecular diagnostics.

This past November, Bellevue University was invited to take part in an Illumina project to beta test their new Microsoft 10 compatible sequencing software. Seven students from the Microbiology, Biology Investigation 205, and Independent Study courses were trained in the entire process, covering DNA extraction, library preparation and Next-Gen Illumina sequencing during this project.

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Students showing off their Illumina swag after successfully completing their DNA sequencing library preps. From left to right: Maddy Vasquez, Morgan Leatherman, Jameson Smith, Nina Patel, Daun Kim, Fabiola Aviles, and Dayana Montano Salama.

I enjoyed the experience and it was great to be able to learn this in an environment where we can try things out and even sometimes fail, but in the end I appreciate getting more hands-on knowledge of the whole sequencing process’ says Fabiola Aviles, a senior Biology major at BU.

Two sequencing runs were performed after upgrading the MiniSeq system. The second run was performed using a pooled library exclusively prepared by Bellevue University students and faculty. Both sequencing runs were successfully completed, and feedback shared with the Illumina team.

 “We truly appreciate the continuous engagement of Dr. John Kyndt and his team during beta testing. Illumina is delighted to empower genomic research of the next generation biologists at BU” says Violet Chu, Senior Product Manager and lead of the Illumina Beta testing team

Dr. John Kyndt who was the lead BU Faculty for this project states that “This was a unique opportunity for both the BU Faculty and students to work closely with a major global company on an innovative sequencing project. We were able to provide Illumina with valuable customer feedback while students had an exclusive chance to learn a new technology and connect with industry leaders in the field of genomics.”

Are you a BU Biology student interested in doing some research or learning Next Gen sequencing yourself? Contact one of the professors at the BU Science labs and we’ll be happy to get you involved!

Last October the Bellevue University Science Labs were honored with an AIA Central States Region Distinguished Award in the Interiors Category.

This prestigious regional award was presented at the regional American Institute of Architect (AIA) 2019 Design Award Ceremony in St Louis. Mike Hamilton (HDR) and Dr. John Kyndt and Diego Kyndt were present to accept the award.

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Mike Hamilton (HDR), John Kyndt (BU) and Diego Kyndt accepting the AIA award.

The BU Science Labs were designed by HDR in close collaboration with the science faculty at BU and were intended to have ‘Science on Display’ and combine a teaching, research and collaboration space.

Shortly after establishing the new lab spaces, the BU Faculty also collaborated with HDR Research on a study, led by Francesqca Jimenez, to understand how the space impacts student learning and the overall  vision of science education at BU. Earlier this year, the Environmental Design Research Association (EDRA) awarded this research project a ‘Certificate of Research Excellence’ (CORE). A paper describing the outcomes from this study is forthcoming.

It is great to see that these lab spaces are being recognized not only locally, but also on a regional scale, and rewarding to see how this space impacts the life of the instructors, visitors, and current and prospective students.

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Sydney Robertson, a recent graduate of the Bachelor of Science in Biology program, recently has had two papers accepted for publication.

Robertson’s paper “Whole-genome sequence of a novel Elioraea species, isolated from a Yellowstone National Park hot spring”, has been published in Microbiology Resources Announcements (MRA), and the paper “Whole-Genome Sequences of the Purple Nonsulfur Photosynthetic Bacteria Rhodobacter capsulatus SP108 and SL Reveal a Need for Reclassification of the Genus” will be published in an upcoming issue of Microbiology, Immunology and Pathology Journal (MIP).

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Sydney Robertson showing off her Illumina swag after completing several successful runs and publishing four genome papers.

It’s a very accomplished feeling doing something outside your comfort zone. I have now a whole new skill set I didn’t even think was possible” Robertson mentioned.

Robertson is the lead author on both papers and collaborated with Dr. Terry Meyer from the University of Arizona and Dr. Robert Ramaley from UNMC.

The experience I had was more than just helpful in the classroom. I was able to collaborate with the professors and other institutions, really learning how to communicate effectively”, she commented. Robertson had previously also published another paper in collaboration with fellow student Shawn Freed. These papers were made possible because of the in-house Illumina Next Generation sequencing that can be done at the BU Science Labs, and the Wilson Enhancement Fund for Applied Research at BU.

The commitment that Sydney has shown for this sequencing project has really paid off. Her enthusiasm and positive attitude kept her engaged and has allowed her to complete these publications even after she graduated earlier this year,” said Dr. John Kyndt, a Professor in the College or Science and Technology and Sydney’s mentor on these projects. “It’s great to see this kind of drive for scientific discovery in our students. I am sure these publications will help her with her future applications to graduate schools or programs.”

Are you a BU Biology student interested in doing some research or learning Next Gen sequencing yourself? Contact one of the professors at the BU Science labs and we’ll be happy to get you involved!

On a vacation trip to New Mexico this summer Dr. Kyndt sampled some water from Dripping Springs in the Organ Mountains to look at the bacterial composition in this pristine natural area.

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Organ Mountains, NM

After returning to the labs at Bellevue University, he grew the samples on bacterial agar plates and noticed several bright orange colored colonies on one of the plates. Intrigued by this, he purified the bacteria and isolated its DNA. After genome sequencing, he found out that this species was closely related to species only found before in dead or diseased fish, so it appeared to be a potential fish pathogen. Since Dr. Moore is more of a fish person (he is an experienced fly fisherman) and knows more about cell infections in general, Dr. Kyndt invited him to join in this study. Together they did some more research and comparison with other species in this genus, which resulted in a new collaborative publication:

Draft whole-genome sequence of a novel Chryseobacterium viscerum strain, isolated from fresh water at Dripping Springs, New Mexico.” was published this week in the journal Microbiology Resource Announcements. The new strain was designated Chryseobacterium viscerum DPS (for Dripping Springs).

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Chryseobacterium viscerum strain DPS

Although this was an exciting find, since no one has ever found this species free living in nature, the most exciting part comes now as they are planning a student-led project to test the pathogenicity of this bacterium.

A more comprehensive metagenomic study of the water and soil samples from Dripping Springs, that looks at all the several hundred bacterial species in the samples, has also been submitted for publication in the journal Microbiology Resource Announcements and is currently under review. Undoubtedly these results will lead to further student research projects at Bellevue University.

The past few weeks we had several news reports about new developments at the BU Sciences.

New Bellevue University worm

One was the Bellevue Leader article about the discovery of a very unique flatworm species at the BU science labs. The worm is a local species that was discovered during regular field work with our students:

https://www.omaha.com/sarpy/bellevue/bu-science-discovers-new-worm-species/article_4604564a-c3e6-501b-9e88-950bf0b2cf83.html

 

Screenshot 2019-08-23 09.45.54Another piece was a Fox 42 News story on the new Sustainability Outdoor Learning Lab that is being developed, and the NET grant that support part of the project. This was based on a recent talk we gave at Green Bellevue:

https://fox42kptm.com/news/local/bellevue-university-to-create-outdoor-sustainability-lab

With the start of a new academic year approaching quickly, more cool stuff will be happening at the BU Science Labs soon. So keep an eye out for more intriguing stories or research projects, and come and join us if you like to do some research yourself!

Every year, Bellevue University recognizes and awards faculty for their contribution to teaching and service to the university. Peers and students have a chance to nominate the faculty for one of four awards. This year the science department took home two of the awards!

The ‘Excellence in Innovation Award’ recognizes innovation by faculty/staff that has a positive impact on the University and/or student learning, and is described as: “Innovation, for the purposes of this award, is defined as the introduction of a new technique/structure/idea/technology that addresses a specific problem or issue and has a demonstrative positive impact”.

The 2019 Excellence in Innovation was awarded to the science team: Dr. Scott Pinkerton, Dr. Tyler Moore, Dr. John Kyndt and Johnny Farnen.

The ‘Excellence in Teaching Award’ recognizes teachers that demonstrate mastery of:

  • High standards of teaching effectiveness.
  • Outstanding or innovative teaching techniques.
  • Positive reputation for teaching from the perspectives of students, colleagues, and alumni.
  • Evidence of sustained commitment to teaching.
  • Evidence of high levels of student learning or achievement.

This year’s Excellence in Teaching Award was given to Dr. Dr. Scott Pinkerton, Dr. Tyler Moore, and Dr. John Kyndt.

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Drs. Kyndt and Moore accepting the awards from Dean Dobransky at the Annual BU All Campus meeting.

The comments of the awards recipients illustrate their passion for science and continuing commitment teaching and innovation:

“We have made significant changes to the science curriculum, lab spaces and overall science education over the past couple of years and our students are now starting to see the benefits of this. We just do our jobs and have fun doing it, but it’s certainly great to see these efforts being recognized by our peers and the University” – Dr. John Kyndt.

“It is wonderful to be recognized by our peers that we don’t just meet standards…we set them!“—Johnny Farnen.

I really enjoy having the opportunity to spend time working closely with students, both in the classroom and the research lab. When I see the growth of a student from the beginning to the end of the program, or hear from graduates about how prepared they were for their jobs or subsequent education, that is the real reward.”—Dr. Tyler Moore.

Story written by Dan Silvia, Communications Manager

Two Bellevue University undergraduate science students have joined the elite ranks of published student researchers. Shawn Freed and Sydney Robertson, both senior Biology students, each received an author credit on “Draft Whole-Genome Sequence of Green Sulfur Photosynthetic Bacterium Chlorobaculum sp. Strain 24CR, Isolated from the Carmel River.” Freed also received an author credit on “Whole-Genome Sequence of the Novel Rubrobacter taiwanensis Strain Yellowstone, Isolated from Yellowstone National Park.”

“It is very rare that undergraduates get published in a scientific peer-reviewed journal, especially as the lead author,” said Dr. John Kyndt, who co-authored the papers with his students. “Even at larger research universities it is rather unusual that undergraduate students get a first author publication during their undergraduate studies. We are able to give students this opportunity because of our smaller class sizes, close professor involvement, and a deliberate focus to integrate more real life research.”

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The science department celebrated the article publications with a pizza party on Tuesday, March 26. Among those in attendance were Dr. Mary Hawkins, University President; Dr. Mary Dobransky, Dean of the College of Science and Technology; Dr. John Kyndt, Dr. Tyler Moore, and Dr. Scott Pinkerton, science faculty; and Johnny Farnen, Science Lab Assistant, as well as the authors themselves.

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