URI center decodes life’s mysteries at genetic level

The Rhode Island Genomics and Sequencing Center sits tucked away on the third floor of the Center for Biotechnology and Life Sciences (CBLS), overlooking the University of Rhode Island’s North Woods.

The presence of room 352 easily passes without notice, the daily grind of academic and research activity drowning out its quiet and unassuming significance.

But inside the modest 1,600-square-foot suite of rooms, the boxy array of equipment and computers resting on tables and desks holds exciting promise for discovery and vast potential to alter the course of human existence.

Every detail about every living thing — human, animal, virus, bacteria, everything — comes down to the sequence of nucleotide bases coded in its DNA.

These foundational building blocks — adenine (A), guanine (G), cytosine (C), and thymine (T) — provide a blueprint that determines the myriad qualities of each living thing; how an organism grows, the traits it develops, how it acquires food and stores energy, the environmental conditions it needs to survive, how it finds mates or defends itself.

If we know what these genes are, we can begin to understand how life processes work. We can use this information to help determine both the causes and cures of disorders, and to develop preventative measures such as vaccines and treatments such as antibiotics to eradicate disease and safeguard against infection.

Through RI NSF EPSCoR research, genetic sequencing is used to learn how climate variability affects marine life and ecosystems — information which is critical to preserving sources of food and water, adapting to environmental changes, and securing economic viability.

“Suppose we want to examine the bacteria in an environment,” says microbiology Professor David Nelson, Department of Cell and Molecular Biology, URI College of the Environment and Life Sciences. “If we take samples, extract their DNA, and sequence one particular gene marker found in all bacteria, we can determine the diversity and abundance of the different microbes based on that gene’s sequence diversity in the different species of microbes.

“Further, we can compare specific gene abundances over the seasons and over years to see the impact of temperature change on a population.”

Additionally, explains Nelson, who founded the Genomics and Sequencing Center and serves as director, we can use gene sequence information with another technique known as reverse transcriptase quantitative PCR to find out how a individual genes in a particular organism respond to rising sea temperatures or the presence or absence of a toxin or disease: “We can answer all sorts of questions at the genetic level.”

Nelson and a couple of colleagues wrote a grant proposal in 2001 for the center. With no facilities in Rhode Island at the time, Nelson says he had to send out samples for sequencing at $16 each, which took not only money, but also time for results that were not always accurate.

Established in 2002, the RIGSC gained EPSCoR funding with the first grant in 2006 and today provides faculty, staff and students with technical and analytical support for molecular biology and genomics research at the nine EPSCoR partner campuses.

The center offers services in robotic sample preparation, DNA library preparation, DNA sequencing (Sanger and Next Generation), fragment analysis, quantitative PCR (or polymerase chain reaction) and in the identification of microbial species and their phenotypes. The center also provides imaging services using transmitted light, epifluorescence and scanning confocal microscopy, and cryostat sectioning of frozen specimens. The center has two full-time employees – Paul Johnson (RIGSC manager) and Janet Atoyan (DNA sequencing technician).

Johnson said the center’s basic mission is to provide and maintain the research tools, and instruct users how to operate them: “Then, they take the data and run with it.”

Pushing science forward

For Associate Professor Chris Lane, URI, Department of Biological Sciences, the Illumina MiSeq Next Generation Sequencer, which can generate sequences of small genome organisms such as bacteria or viruses, has been particularly helpful.

“We’ve used it a lot to check samples before spending tens of thousands of dollars sequencing them more deeply,” Lane said. “It’s also been great for quick projects and samples we need quickly for preliminary data. The combination of fast turn-around and Janet’s expertise with the library construction side of things has been extremely helpful.”

URI Professor Marta Gomez-Chiarri, department chairman of Fisheries, Animal & Veterinary Science, says the center plays an integral role in her research program and her lab uses the equipment on nearly a daily basis.

She, too, credits Johnson and Atoyan for their technical expertise: “They provide excellent training to undergraduate and graduate students, allowing us to use techniques that we were unable to use before due to lack of expertise in the laboratory.”

According to Nelson, both Johnson and Atoyan are essential to the center’s success, making it an invaluable resource for the state’s researchers. They pay attention to detail, ensure samples are made properly and work closely with researchers to resolve any problems.

Beyond cutting research costs and making the equipment conveniently accessible, Nelson says the center also holds value in building research capacity, both in attracting faculty and students and strengthening grant proposals.

“For someone who does molecular-related work, if you can say we have this genomics and sequencing center, their eyes light up,” Nelson says. “When kids look at it for grad school, they notice that they can do DNA sequencing on campus. And, it helps when we apply for grants.”

The benefits extend beyond URI campus to the rest of the state, he adds. Any researcher at the other eight EPSCoR partner institutions can send samples to the center. With a common, shared resource, no individual school has to spend inordinate sums of money to acquire the capabilities.

For example, he points to the Illumina MiSeq at URI and the Illumina HiSeq at Brown University. The MiSeq is good for sequencing small genome organisms like bacteria or viruses. In comparison, the HiSeq is used for large genome sequencing — it can do humans, trees or mice.

Whatever the need, both Nelson and Johnson say, having the technological capability in state, guided by the proper expertise, and at affordable and competitive rates benefits all researchers in multiple disciplines, from microbiology and engineering to physics and pharmacy.

Referring to the technology, Johnson says, simply, “It’s allowed science to go forward here in Rhode Island.”

By Amy Dunkle | from the Spring 2015 issue of The Current