- Your Voice
What happens when you bring a medical doctor, an immunologist and a marine biologist together to take medicine from the lab to the patients? Great things.
University of Arizona researchers have been awarded a $200,000 two-year seed grant by theFlinn Foundation through its Promoting Translational Research in Precision Medicine grants program to find out how a virus that flies under the radar of the body's immune defense may influence health, disease and even behavior. The goal of the seed grant program is to foster collaborative efforts between physician-scientists and bench researchers in order to translate findings more rapidly to actual patient treatments.
"Precision medicine" – also known as "personalized medicine" – is one of the strategic initiatives of the UA's Never Settle strategic plan, with considerable investments planned for new infrastructure and 50 new faculty hires over the next 10 years. Precision medicine aims at closing the gap that currently exists between scientific advances and clinical practice. The more researchers discover about the molecular mechanisms underlying diseases, the clearer it becomes that one treatment does not fit all. By integrating such knowledge with clinical data on individual patients, precision medicine entails tailoring treatments to individual cases and improving outcomes for the patients.
The unique research team consists of UA associate professor of medicine Ken Knox, who specializes in pulmonary medicine and has a strong track record in clinical and translational research; UA associate professor of immunobiology, BIO5 Institute member and biomedical researcher Felicia Goodrum, who is an expert in viral persistence; and UA associate professor of ecology and evolutionary biology and BIO5 member Matthew Sullivan, an expert in viral metagenomics.
The team will unravel which viruses make their homes in the lung without causing symptoms. Specifically, they will home in on one such virus, the cytomegalovirus, known as CMV, which belongs to the herpes virus family.
The human body is home to a vast number of bacteria, viruses and fungi that collectively make up the human microbiome. Much of our microbiome does not cause disease, but rather is critically important to maintaining human health. Recent studies in humans document the enormous impact bacteria have on normal health (e.g., obesity), disease states (e.g., diabetes, gastrointestinal disorders), and even behavior. The role of viruses, by contrast, represents uncharted frontiers for study.
Human CMV is one of eight human herpes viruses and infects 60-90 percent of the population worldwide and, like all herpes viruses, persists in the infected host indefinitely by way of a latent infection. CMV’s primary infection of healthy individuals is typically asymptomatic and, therefore, goes completely unnoticed. When CMV is reactivated from latency to an active state of replication, there are life-threatening disease risks in immunocompromised people, including transplant and cancer patients. CMV infection is also the leading cause of infectious disease-related birth defects, affecting 1 percent of live births in the United States.
Persistent viruses represent emerging health threats that contribute to chronic inflammation, cellular stress and cancer risk. In addition, latent viral coexistence is just beginning to emerge in association with age-related pathologies, including atherosclerosis, immune senescence and frailty. Health costs of persistent viral infections, whether chronic or latent, can be significant.
Knox, Goodrum and Sullivan will study CMV as a model of persistent viral infection upon which to base questions related to how to specifically prevent lung infections.
Just as genetic makeup is different among individuals, so are their immunological reactions to invading viruses, which in turn influences how disease states manifest from individual to individual. By using advanced informatics to analyze metagenomic data sets from the study, the team will investigate correlations between the presence of human CMV and what scientists call the background virome: the "zoo" of viral populations present in a given individual.
“Translational research – moving discoveries from the lab to patient care – is a crucial element of precision, or personalized, medicine as well Arizona’s bioscience strategy,” said Jack B. Jewett, president and CEO of the Flinn Foundation, a philanthropic organization committed to improving the quality of life in Arizona to benefit future generations. “This exciting collaboration among Drs. Knox, Goodrum and Sullivan is an outstanding example of a potentially groundbreaking research project that could ultimately yield great benefits to human health.”
“This study is extremely important and timely, as known and yet-to-be discovered viruses are undoubtedly influencing human health and contributing to disease states," said Janko Nikolich-Zugich, Elizabeth Bowman Professor in Medical Research and head of the UA Department of Immunobiology.
Fernando Martinez, MD, UA Regents’ Professor of Pediatrics and director of both the Arizona Respiratory Center and the BIO5 Institute, agreed, adding, "Defining the viruses present in the human lung will be an important step in expanding our knowledge base of the pulmonary virome. In addition, techniques used to identify viruses hold promise for rapid diagnostics and treatments."
Other members of the study team at the UA include PhD candidates Katie Caviness and Ann Gregory, senior research scientist Bonnie Poulos, Heidi Erickson, and Lance Nesbit. The current study also will examine viral reservoirs in the context of lung transplants and thus is likely to have broad implications for our understanding of pulmonary immunity and rejection.
The greatest battle in Earth's history has been going on for hundreds of millions of years, isn't over yet, and until now no one knew it existed, scientists reported today in the journal Nature.
In one corner is the Earth's most abundant organism: SAR11, an ocean-living bacterium that survives where most other cells would die and plays a major role in the planet's carbon cycle. It had been theorized that SAR11 was so small and widespread that it must be invulnerable to attack.
In the other corner, and so strange looking that scientists previously didn’t even recognize what they were, are "Pelagiphages," viruses now known to infect SAR11 and routinely kill millions of these cells every second. And how this fight turns out is of more than casual interest, because SAR11 has a huge effect on the amount of carbon dioxide that enters the atmosphere, and the overall biology of the oceans.
"There's a war going on in our oceans, a huge war, and we never even saw it," said Stephen Giovannoni, a professor of microbiology at Oregon State University. "This is an important piece of the puzzle in how carbon is stored or released in the sea."
The paper in Nature describes four previously unknown viruses that infect SAR11. To prove the viruses were as abundant as their hosts, OSU teamed up with researchers at the University of Arizona’s Tucson Marine Phage Research Lab, led by Matthew Sullivan, who had developed accurate methods for measuring viral diversity in nature.
The analysis shows that the new viruses – like their hosts – are the most abundant on record. Sullivan is an assistant professor in the UA's department of ecology and evolutionary biology with a joint appointment in the department of molecular and cellular biology.
"The methods and datasets developed by Matt's lab at the University of Arizona will make it possible for a generation of marine microbiologists to more accurately determine viral distributions in nature," Giovannoni said. "It's a major step forward for the field."
Giovannoni's group discovered the Pelagiphage viral families by using "old-fashioned" research methods, growing the cells and viruses in a laboratory, instead of the tools of modern genomics, and found the new type of virus.
"Because they are so new, these viruses were virtually unrecognizable to us based on their DNA," Giovannoni said.
"The viruses themselves, of course, appear to be just as abundant as SAR11," he added. "Our colleagues at the UA demonstrated this with new technologies they developed for measuring viral diversity."
Sullivan explained the method for discovering viruses in the oceans based on their genomes his group developed over four years is at least 1,000 times more accurate than previous methods.
Much of the analyses and datasets enabling the discovery of the viruses were generated by Bonnie Hurwitz, a former graduate student of Sullivan’s who is now program director of health informatics at the Arizona Health Sciences Center, with help from research scientist Bonnie Poulos and other members of the Tucson Marine Phage Laboratory.
Their work, soon to be published in the open-access journal PLoS One, resulted in the Pacific Ocean Virus dataset. This dataset, Sullivan explained, is the viral equivalent of the Global Ocean Sampling Expedition by former human genome researcher J. Craig Venter, who sailed across the world's oceans sampling, sequencing and analyzing the DNA of the microorganisms living in these waters.
The new findings on SAR11 disprove the theory that the bacteria are immune to viral predation, Giovannoni and his co-authors said.
"In general, every living cell is vulnerable to viral infection," said Giovannoni, who first discovered SAR11 in 1990. "What has been so puzzling about SAR11 was its sheer abundance, there was simply so much of it that some scientists believed it must not get attacked by viruses."
What the new research shows, Giovannoni said, is that SAR11 is competitive, good at scavenging organic carbon, and effective at changing quickly to avoid infection. Because of this, it thrives and persists in abundance even though it's constantly being killed by the new viruses that have been discovered.
SAR11 has several unique characteristics, including the smallest known genetic structure of any independent cell. Through sheer numbers, this microbe has a huge role in consuming organic carbon, which it uses to generate energy while producing carbon dioxide and water in the process. SAR11 recycles organic matter, providing the nutrients needed by algae to produce about half of the oxygen that enters Earth's atmosphere every day.
This carbon cycle ultimately affects all plant and animal life on Earth.
"Because of their huge numbers, these cells are an important part of models that aim to understand and predict long-term patterns of carbon sequestration in the oceans," Giovannoni said.
"Microbes fix half of the oxygen in the air we breathe and drive every biogeochemical cycle that fuels Earth," Sullivan added. "Most of this happens in the oceans, and it turns out the most abundant microbes on the planet are the SAR11 bacteria."
Other contributors to this research included scientists at the University of California, San Diego’s National Center for Microscopy and Imaging Research and the Monterey Bay Aquarium Research Institute, which provided opportunity to sample viruses from nature.
Funding for the methods development and genomic sequencing was provided by the Gordon and Betty Moore Foundation Marine Microbiology Initiative and the Department of Energy Joint Genome Institute.
Best Police Officer
I attended the Chamber of Commerce forum for Marana Town Council candidates. I was late, but I was there long enough.
The Golder Ranch Fire District has opened a new fire station in Oro Valley.