Genomics Technology Core

Technique connects DNA instructions to biological architecture in space: Core collaboration maps the future

November 10, 2021 By Lauren Hines in Research Tags: bioinformatics, Genomics Technology Core, Spatial Sequencing

By Lauren Hines | Bond LSC

The brain is a unique challenge. It has billions of cells with billions of different functions, making it hard to understand what is going on underneath. MU cores now offer 10X Genomics Visium technology which allows researchers to lay genetic data over an image of a tissue sample creating a map of the brain at a genetic level — or any other organ you can think of.

“Spatial transcriptomics is a great example of how science has become more collaborative in nature, certainly, and that requires cross-disciplinary interaction between researchers and other technologies,” said Nathan Bivens, director of the Genomics Technology Core at Bond LSC.

Teamed up with the Advanced Light Microscopy Core and Bioinformatics and Analytics Core, Bivens’s core played a key part in developing spatial sequencing on campus. The technique maps physical characteristics of any tissue to its corresponding gene expression, so researchers can understand what’s going on at the genetic level.

The collaboration started last year when researchers across the country reached out to the individual directors at Bond LSC. Each could handle their part of the project but realized they couldn’t do it alone.

“There are very few places that have all three of those groups, especially in one building where they work so closely together,” said Lyndon Coghill, director of the Bioinformatics and Analytics Core.

Spatial sequencing provides scientists with a way to point at tissue and say where which gene is being expressed and identify cell types. Researchers can understand how these cells are interacting with each other and what that means for the function of the organ overall.

“We can actually see which part of that tissue those differences are occurring in, which can dramatically increase our biological understanding of what’s happening because certain types of tissues are known to do certain things biologically. By connecting those pieces, it’s sort of like adding that final puzzle piece to getting a full picture of what’s happening between these things,” Coghill said.

Before spatial sequencing, there were a few ways to analyze the genes in tissues, but no real way to see what traits those genes were connected to or how these genes were interacting with each other.

While tissues have different cell layers and a lot going on, researchers would have to mix that all up kind of like using a blender. Take a simple leaf for example. It would be ground up with mortar and pestle then put in a solution to be sequenced. By analyzing the mixture, they could see all the genes together, but lose definition and cell-specific expression of genes. Essentially, it created a genetic average of everything, and you couldn’t see how genes were expressed closer to the stem versus farther away or in a specific structure.

“Spatial transcriptomics is just the right approach to study gene expression inside diverse cell populations like the brain or small brain regions,” said Alexander Jurkevich, associate director of the Advanced Light Microscopy Core. “It really opens great perspectives for studying, knowing and learning new functions.”

The key to this technology is having equipment and expertise for imaging, DNA analysis and data organization all under one roof.

The process starts in the Advanced Light Microscopy Core where Jurkevich thinly slices frozen tissue, puts these slices onto very special slides and stains it with a dye so it can show up underneath the microscope. After taking some pictures, it gets sent off to Bivens in the Genomics Technology Core.

Core staff then enzymatically removes the cell membranes of the tissue to release genetic material. Remember those special slides? Even though the tissue is now broken down, those slides have dots underneath the tissue that capture the expressed genes and assign a unique barcode to each point of the tissue. That way, researchers can analyze the data but still know which gene goes where.

Finally, all this data — from the DNA analysis, the images and the barcodes — all go to Coghill in the Bioinformatics and Analytics Core. Coghill and his team work to organize the data and create a map of the tissue and its genetics.

Jurkevich, Bivens and Coghill are looking towards seeing this technology map tumor treatment, Alzheimer’s in the brain and other disease studies.

“I really do think this connection of the raw data with a biological architecture is where we’re going to make those kinds of leaps forward not just in discovery, but also in potential clinical applications,” Coghill said.

Now, the cores have finished their first attempt at this huge collaboration. So far, it’s been successful, but they want to streamline the process. The biggest hurdle has been finding times when all three cores are available to work on a new project.

“Working on this technology was a great opportunity to work with different research cores … for us to learn something new and generate a product which is unique and very complex,” Jurkevich said.

Spatially resolved transcriptomics technology was declared as the Method of the Year 2020 by the Nature Methods journal.

#IAmScience Nathan Bivens

April 2, 2021 By Lauren Hines in #IAmScience Tags: Genomics Technology Core, sequencing

By Lauren Hines | Bond LSC

With water up to his waist, Nathan Bivens is in his element fly fishing as he waits for a trout to grab onto the end of his line.

Bivens picked up this hobby growing up in his hometown of Cassville, which is also where his path to the Bond Life Sciences Center began. The Genomics Technology Core Director is the kind of person who will always be there when others need him.

“I really enjoy working with a variety of researchers across campus,” Bivens said. “My role and work in a core facility allow me to interact with hundreds of researchers…And they’re just doing some great science.”

Leaving southwest Missouri in 1990, Bivens went to MU to get his bachelor’s in molecular biology. After completing his master’s at the University of Illinois in 1997, he applied to the university’s Center for Comparative and Functional Genomics to coordinate high throughput DNA sequencing projects.

Two years later, he and his wife moved back to Columbia. After working as a senior research specialist and associate director at MU, Bivens became the Genomics Technology Core Director in 2018.

The Genomics Technology Core facility is an institutional resource to educate and assist researchers in the use of sequencing technologies. Its services employ revolutionary advances in next-generation DNA sequencing to enable the sequencing of genomes and transcriptomes from whole organisms down to a single cell.

“Twenty-five years ago, when I started doing this, the technology was completely different,” Bivens said. “I’ve seen technologies come and go, but it’s always exciting because I have the opportunity to learn something new. It keeps my mind active.”

The genomics revolution has promoted the development of the technologies currently used to answer today’s research questions. Short-read sequencing platforms now provide billions of sequences in a single run at a fraction of the cost of previous technologies, which drives the discoveries being realized in the fields of personal genomics and basic research.

Many scientists rely on the Genomics Technology Core to help advance their research.

“In this position, I have the opportunity to interact with many different folks on a daily basis,” Bivens said. “It’s always helpful, and I enjoy that.”

Even beyond clients and collaborators, Bivens helps others with his time, knowledge and advice.

“Nathan is one of the wisest people I know,” said Sam Bish, senior technology transfer manager in the Technology Advancement Office. “He’s very soft-spoken, doesn’t talk himself up and puts others first.”

Before Bish realized they worked in the same building, he first met Bivens at the Open Door Church more than six years ago. At the time, Bivens was a deacon at their church and now serves as pastor of the church.

“He’s someone that I often go to for advice, mainly about life, but for work as well,” Bish said. “I trust that he’s not going to lead me down a path that he wouldn’t go down himself, meaning that he’s not out for his own personal gain. He’s only looking to help me.”

Another big part of Bivens’ life is his family. He spends a lot of his time taking his daughter to her volleyball practices and volunteering as a line judge during games. He and his wife even help her with her small cake business.

“The thing I admire in Nathan most is how good he is as a parent to his daughter,” Bish said. “She didn’t become an amazing baker and cook on her own, but he and his wife saw that was her interest and they’ve poured in resources to help her grow in that area.”

Looking back at the past 25 years, Bivens appreciates the work he’s done both in and out of the lab.

“I know many of our researchers feel that the core facilities are an asset to the work they do and that they do view us as essential for research at MU,” Bivens said. “So that, to me, gives me a sense of pride.”

Whether it’s help on a genomics project or parenting advice, Bivens knows how to be there.

University grant brings faster, cheaper genome sequencing

September 4, 2019 By Mariah Cox in Research Tags: Genomics Technology Core

Bivens & Warren — Nathan Bivens, Director of the Genomics Technology Core, and Wesley Warren, Bond LSC primary investigator. | Photos by Mariah Cox & Erica Overfelt | Bond LSC

By Mariah Cox | Bond LSC

The discoveries from research capture the public’s and other scientist’s attention, but what about the tools, instruments and data management systems that provide more efficient means of getting there?

A new genome sequencing instrument is on its way to the Bond Life Sciences Center thanks to a Tier 1 grant from the UM system’s mission to enhance the ‘well-being for Missouri, the nation and the world through transformative teaching, research, innovation, engagement and inclusion’.

Wes Warren, primary investigator in the Bond LSC, led the effort to speed up the turnaround time for genome sequencing and lower the overall cost. The proposal for NovaSeq instrumentation additionally includes purchasing more data storage to keep up with researchers’ demand for the technology.

“This is an issue that has been noticed in the last three or four years around being able to generate the data in a high throughput fashion. A lot of our genomics researchers were required to seek these services off-campus,” said Nathan Bivens, Director of the Genomics Technology Core. “As part of this strategic initiative, we saw an opportunity for campus to invest in this instrument, make it available and then continue to build our own genomics resources here on this campus.”

With his experience with the McDonnell Genomic Institute at Washington University in Saint Louis for the past 17 years, Warren was the person to lead the charge in bringing this technology to MU.

“I was involved in some of the later stages of curating the human genome and I’ve been involved in many genome sequencing efforts at the McDonnell Genomic Institute, not only that but high-throughput sequencing in populations,” said Warren. “My work mostly revolved around comparative genomics. The experience factor that I brought to this proposal is knowledge of how to do high throughput sequencing and how to curate the data.”

Since the first human draft genome in the 90’s, there have been constant developments in sequencing technology to speed up the process and to do so at a lower cost. Sequencing figures out the order of A’s, C’s,G’s, and T’s that make up the DNA nucleotides, or bases, that define a genome that codes to build an organism.

Genomic and single-cell sequencing machines are ‘disruptive technologies’ which allow scientists to essentially have a blueprint of all of the genes that make up any given organism. These blueprints can be used for a variety of scientific purposes to study issues ranging from cancerous mutations to drought resistance in plants.

The data being generated from such technologies is allowing researchers to better understand scientific complexities such as cancers.

“We have an Illumina instrument that’s a different type of format in terms of its capability. It produces fewer bases per flow cell and as a result of that it’s more expensive,” said Warren. “It’s simply a question of cost here; the technology of the NovaSeq has improved in terms of the base accuracy but the main reason is that with more bases per flow cell, the more experiments you can do.”

The current technology in MU’s Genomics Technology Core costs about 30 percent more to complete similar sequencing and takes longer. The new technology can complete thousands of sequences at once, which means it will generate the data needed for publishing discoveries in a more timely fashion.

This cost-effective high throughput technology will allow researchers across the UM System to increase the number of samples they can test and to find genes of significance and traits of interest at a much faster rate.

“Since 2008, we’ve continued to see an increase in the amount of data that’s being generated on campus and the number of publications that are resulting from genomics research and data and I don’t think that’s going to slow down anytime soon,” said Bivens. “In five to 10 years I think we will still be generating more sequencing data especially with the new NextGen Precision Health Institute here at MU. We’re seeing more and more growth in areas which are going to use this type of technology.”

Inevitably, housing this technology at MU will create a higher demand for sequencing through the Genomics Technology Core Facility. To keep up with the demand for this data, Bivens said the facility is purchasing more data storage, restructuring the lab and potentially looking for an additional hire to help process the workload.

As for when the technology will be installed on campus and the DNACF personnel trained to use it, Bivens hopes to be ready to receive samples at the end of September, beginning of October.

This instrumentation is funded by the UM System’s and all four campuses strategic investment for research and creative works.

A program that pushes science forward

May 16, 2019 By Danielle Pycior in Research Tags: Genomics Technology Core

By Danielle Pycior | Bond LSC

It’s the little things we take for granted, and for science experiments, one of those are enzymes.

French chemist Anselme Payen discovered the first enzyme, diastase, in 1833, but it wasn’t until 1877 that the word enzyme was used. While it’s a compact name, it’s really a category of proteins produced by living organisms that speed up chemical reactions regardless of whether it’s in the body or the test tube. The way these proteins are folded make their chemical interaction very specific, but when they bind with the right molecules, they speed up reactions hundreds or thousands of times. Since their first discovery, researchers have found thousands more enzymes that play an integral role in even more scientific discoveries.

A program on the second floor of Bond Life Sciences Center gives scientists the small something they need to make those discoveries. The Enzyme Freezer Program — part of the MU Genomics Technology Core— began in the 1990s and has grown to provide enzymes for 120 different labs across the University of Missouri campus.

Though it has become a staple in the science community, allowing researchers to walk down the stairs or make a call across campus to find what they need, this convenience helps quickly and quietly move science forward.

“Modern research requires a lot of expensive things,” said Kate Shipova, freezer program specialist. “For end-users, it’s convenient because they can come and buy something immediately.”

Shipova spends her days talking with sales representatives and vendors, fixing problems and finding researchers the substances they need to continue searching for answers. The lab is lined with refrigerators and freezers, all stocked full of substances used every day in labs around campus and around the world for anything from genome sequencing to nucleic acid purification.

Nowadays, it’s normal to have fairly easy access to any substance scientists may need for their research, but generations ago this would have been difficult to imagine. Walter Gassmann, Bond LSC interim director and professor of plant sciences, recalled visiting a colleague in Morocco who works for its government. She has to order everything she needs for her lab an entire year in advance, while MU researchers can get what they need on a whim if needed.

“I think it’s too easy to take things for granted that was more work before, and this really accelerates your research,” Gassmann said. “It helps not having to plan far in advance.”

The program has numerous chemicals in stock and the ability special order almost any enzyme a researcher may need, shipping it for free and at a discounted price. Nathan Bivens, assistant director of the MU Genomics Technology Core, said most of the chemicals are used for molecular biology or proteomics research, so the common reagents they keep in stock work with RNA and DNA.

“It’s really an advantage to a researcher who wants to make that grant dollar stretch since it’s a much more affordable option,” Bivens said. “Plus, it’s here and readily available. You have the ability to come here and get the reagent quickly.”

In many parts of the world, researchers aren’t so lucky to work in a place with resources this readily available, with a staff dedicated to helping. Shipova and Bivens work to make researchers’ lives easier by providing the chemicals they need at an affordable price, and scientists such as Gassmann appreciate all of the hard work they do.

“In other countries, an enzyme has to be shipped, and it can get stuck in customs and it doesn’t get treated right. Here things are so much easier.”

What was once only a dream for scientists who couldn’t so readily access the tools they need is now a common and easily accessible program. While new technologies and methods continue to take the spotlight, freezer programs and those who run them will continue working in buildings like Bond LSC to quickly make reactions happen.