Challenging a long-held convention, University researchers have shown they can inhibit Influenza A by targeting its genomic RNA with “antisense” compounds.

Their findings, highlighted on the cover of Nucleic Acid Therapeutics, offer scientists a new way to attack an increasingly drug-resistant pathogen that causes an estimated 250,000 to 500,000 deaths a year.

“Antisense” compounds are synthesized with nucleotides, the building blocks of nucleic acid, often shown as various combinations of A, U, G, and C. When the compounds – called antisense oligonucleotides (ASOs) – bind to the targeted genomic RNA, they block its ability to replicate.

The collaboration, involving the labs of Douglas Turner, professor of chemistry;  Luis Martinez-Sobrido, associate professor of microbiology and immunology; and two researchers in Poland, reported that “antisense” compounds targeting one of the virus’ eight genomic RNA segments caused a five- to 25-fold reduction of Influenza A virus in cell cultures.

“That’s a big difference,” Martinez-Sobrido says. “When mice are infected with 10,000 viruses, they all die. However, with 25 times less virus, all animals can survive infection and they don’t even develop symptoms.”

The most effective of the antisense compounds ranged from 11 to 15 nucleotides long, and were not toxic to host cells.

To date, most “antisense” research has focused on targeting messenger RNA; the only two FDA approved “antisense” therapeutics – vitravene for use against a retina inflammation, and mipomersen to reduce cholesterol – do so.

“To my knowledge, this is the first published paper where ASOs target internal regions of genomic influenza viral RNA,” says Turner. “This genomic RNA has not been targeted because the dogma was that it is completely encapsulated by the viral nucleoprotein, and therefore is not accessible.”

But recent evidence has suggested – as this study demonstrates – that influenza genomic RNA is vulnerable, at least at certain points in the virus’ life cycle. For example, packaging of the influenza viral genome is “mediated by RNA-RNA interactions” among all eight segments, Martinez-Sobrido says. “So clearly during the replication cycle of influenza virus, the genomic RNA is at least partially naked.”

Influenza viruses have shown a remarkable ability to mutate and become resistant to current antiviral drugs.

Martinez-Sobrido believes ASO’s could be more difficult for viruses to bypass. “If an oligonucleotide is targeting a segment of genomic viral RNA that is especially important, any mutation that altered that RNA would likely be lethal to the virus,” Martinez-Sobrido says. And if additional ASOs could simultaneously attack three or four other segments of genomic viral RNA, the virus’ task would be even more complicated.

The study was supported with funding from an NIH Fogarty International Research Collaboration Award received by Turner and Elzbieta Kierzek, associate professor at the Institute of Bioorganic Chemistry Polish Academy of Sciences. It was also supported by a 2014 University Research Award to Turner and Martinez-Sobrido. The team also included Prof. Ryszard Kierzak of the Polish Academy of Sciences, and University postdoctoral fellows Aitor Nogales in Martinez-Sobrido’s lab and Elzbieta Lenartowicz, the lead author, in Turner’s lab.

For their work in this area, Turner and Ryszard Kierzak have been named recipients of the Poland – U.S. Science Award this year from the American Association for the Advancement of Science (AAAS) and the Foundation for Polish Science. 

Martinez-Sobrido and Turner are both members of the University’s Center for RNA Biology, which draws more than 20 faculty members from seven departments to conduct interdisciplinary research into the function, structure, and processing of RNA. The center is directed by Lynne Maquat, professor of biochemistry and biophysics, who is considered a pioneer of nonsense-mediated mRNA decay.

Scientists working in all neuroscience fields across the University will present promising ideas, programs, and services at a Dec. 1 retreat sponsored by the Ernest J. Del Monte Institute for Neuroscience. The presentations and feedback will help direct priorities and goals for the Institute’s upcoming strategic plan.

All are invited to attend the retreat from noon to 6 p.m. at  the Hilton Garden Inn at College Town.

Presentations from researchers in biomedical genetics, brain and cognitive sciences, dentistry, medical optics, neurology, neuroscience, neurosurgery, ophthalmology, pediatrics, pharmacology and physiology, and psychiatry will be grouped in five sessions, addressing:

• neurodevelopmental disorders
• regenerative neuroscience
• aging neuroscience
• cognition, circuits, and addiction
• vision and pain

RSVP by Nov. 28 to  Kathleen Jensen at Kathleen_jensen@urmc.rochester.edu or 276-8730. Click here for more information.

A study led by Irfan Rahman, professor of environmental medicine, suggests that electronic cigarettes are as damaging to gums and teeth as conventional cigarettes are.

Published in Oncotarget, it is the first scientific study to address e-cigarettes and their detrimental effect on oral health on cellular and molecular levels.

Most e-cigarettes contain a battery, a heating device, and a cartridge to hold liquid, which typically contains nicotine, flavorings, and other chemicals. The battery-powered device heats the liquid in the cartridge into an aerosol that the user inhales.

Electronic cigarettes continue to grow in popularity among younger adults and current and former smokers because they are often perceived as a healthier alternative to conventional cigarettes.

“We showed that when the vapors from an e-cigarette are burned, it causes cells to release inflammatory proteins, which in turn aggravate stress within cells, resulting in damage that could lead to various oral diseases,” explained Rahman, who last year published a study about the damaging effects of e-cigarette vapors and flavorings on lung cells and an earlier study on the pollution effects.  “How much and how often someone is smoking e-cigarettes will determine the extent of damage to the gums and oral cavity.” Read more here.

A study by University researchers demonstrates for the first time that 4-aminopyridine (4AP), a drug used to treat patients with multiple sclerosis, has the unexpected property of promoting recovery from the kind of acute nerve damage sustained in car accidents, sports injuries, or in combat.

The study, authored by John Elfar,  associate professor of orthopaedics, and Mark Noble, Martha M. Freeman, M.D., Professor in Biomedical Genetics, and their laboratory team, appears in EMBO Molecular Medicine. They found that daily treatment with 4AP promotes repair of myelin, the insulating material that normally surrounds nerve fibers.

The finding may address unmet needs of traumatically injured patients for whom the current standard of care  is “watchful waiting” to determine whether a nerve has the ability to spontaneously recover, or if it will require surgery.

The problem, says Elfar, is that “the patient who may recover is recovering so slowly that nerve-dependent tissues are in jeopardy, and the patient who needs surgery has to wait for weeks for the diagnosis that surgery is appropriate.  That delay means that surgery is less effective.” Read more here.

John Nichol has joined the Department of Physics and Astronomy as an assistant professor after a postdoctoral fellowship at Harvard University. An experimental condensed matter physicist, Nichol investigates the quantum mechanical behavior of nanoscale objects. He has developed new techniques for nanoscale magnetic resonance imaging, and also has explored the use of individual electrons in semiconductors as quantum bits, or qubits, which has applications for quantum computing. His recent work demonstrated precise entanglement or “spooky action at a distance” between individual electrons in a semiconductor, laying a foundation for a future quantum computer. He received the John Bardeen Award for outstanding research in condensed matter physics as a doctoral student at the University of Illinois at Urbana–Champaign.

River Campus Libraries and the Office of Global Engagement have recently partnered to acquire a license to InCites, a new bibliographic tool that allows users to analyze and measure the University’s international and domestic research connections and impact.

InCites uses Web of Science data to deliver reliable metrics and indicators across research activities, and will help the University to identify possible new partnerships based on areas of disciplinary strength and existing collaboration.

River Campus Libraries will provide support for researchers and scholars across the University who wish to use InCites to connect and collaborate with colleagues in other institutions, and the Office for Global Engagement can advise and assist on the development of institutional collaboration internationally. For further inquiries and assistance, please email global@rochester.edu or ndimmock@library.rochester.edu.

University students and faculty interested in commercializing their research can learn from an expert at a presentation, “Succeeding at SBIR/STTR Grants,” at 9 a.m., November 30, at Hawkins-Carlson Room of Rush Rhees Library.

The Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs offer competitive awards to help startups and small businesses explore their technological potential. Each year 11 participating federal agencies award $2.5 billion in SBIR/STTR funding.

Guest speaker Kirk Macolini is founder and president of Centurion Technology, a consulting firm that specializes in helping small innovative companies obtain SBIR/STTR funding.  He has developed proposals that have resulted in nearly 300 federally funded projects.

The presentation is sponsored by High Tech Rochester and co-sponsored by the University. To attend the presentation, RSVP here.

The Environmental Health Sciences Center (EHSC) has funds to support a limited number of meritorious pilot projects focused on “Environmental Agents as Modulators of Human Disease and Dysfunction.”

Proposals are encouraged that use emerging technologies or the EHSC’s Human Exposure Facility to investigate how the environment modifies stem cells, affects early life origins of adult disease, and host-pathogen interactions.

The deadline for submitting initial applications is December 9, 2016. Contact Michael O’Reilly for more information. Click here for the full RFA.

The Breast Cancer Coalition offers funding for two breast cancer research grants, one a maximum of $25,000 for pre- and post-doctoral trainee/fellows and the other $50,000 for faculty applicants.

The coalition is committed to supporting and furthering breast cancer research. Four focus areas have been prioritized: cause, prevention, prevention of metastasis, and cure.

Coalition grant money is intended for use as “seed money” to fund innovative new projects with potential to yield significant medical breakthroughs. Click here for the full RFP. Deadline for submissions is December 30, 2016.

Kathryn Sparrow, Geosciences, “Assessing the Contribution of Methane Sourced from Ancient Carbon in the Alaskan Arctic Ocean to the Modern Atmosphere Using Natural Radiocarbon Measurements.” 3:30 p.m., Nov. 30, 2016. 316 Hutchison Hall. Advisor: John Kessler.

Nahal Maleki Tabriz, Electrical Engineering, “Channel-aware distributed detection in wireless networks with correlated observations.” 3 p.m., Dec. 1, 2016. 426 Computer Studies Building. Advisor: Azadeh Vosoughi.

Due to the Thanksgiving holiday, there will be no Research Connections next week.

Today: Center for Integrated Research Computing (CIRC) symposium, 11:30 a.m. to 1 p.m., Goergen 108. Thomas Howard of electrical and computer engineering will discuss learning models for robot decision making. Joseph Ciminelli of biostatistics and computational biology will discuss analysis of text documents over social networks.

Today: “Familial hypercholesterolemia and funding from the Patient Centered Outcomes Research Institute,” by Robert C. Block,  associate professor of public health sciences. Public Health Grand Rounds. Noon to 1 p.m., Helen Wood Hall Auditorium (1w-304).

Nov. 30: “Fossils and Authenticity in the Age of Jurassic Park,” Elana Shever, Humanities Center Fellow, Work-in-Progress Seminar Series. Noon to 2 p.m., Humanities Center Conference Room D. Lunch will be provided. Please RSVP to humanities@rochester.edu.

Nov. 30: “Succeeding at SBIR/STTR Grants,” Kirk Macolini, founder/president, Centurion Technology. 9-11:30 a.m., Hawkins-Carlson Room, Rush Rhees Library. RSVP here.

Nov. 30: “How to Prepare a Poster for Presentation.” Denham Ward, professor emeritus of anesthesiology and of biomedical engineering. 11:30 a.m. to 1 p.m.  Center for Experiential Learning (2-7544), Medical Center.

Dec. 1: Del Monte Institute for Neuroscience retreat, to hear presentations on promising neuroscience-related research from scientists across the University.  Noon to 6 p.m., Hilton Garden Inn at College Town. RSVP by Nov. 28 to  Kathleen Jensen at Kathleen_jensen@urmc.rochester.edu or 276-8730. Click here for more information.

Dec. 1: Deadline to apply for Humanities Center semester-long fellowships.  Proposals should address the theme of “Memory and Forgetting.” To apply, click here.

Dec. 1: Center for AIDS Research eighth annual HIV/AIDS Scientific Symposium. 10 a.m. to 3 p.m. Keynote speakers in the Class of ’62 Auditorium (G-9425) and a poster session (11 a.m. to 12:30 p.m.) in Flaum Atrium. Contact Laura Enders with questions or for more information.

Dec. 2: Applications due for Collaborative Pilot Studies and Junior Investigator Awards from the Wilmot Cancer Institute. Contact Pam Iadarola for more information.

Dec. 9: Deadline for initial applications for pilot project funding from the Environmental Health Sciences Center to investigate how the environment modifies stem cells, affects early life origins of adult disease, and host-pathogen interactions. Contact Michael O’Reilly for more information. Click here for the full RFA.

Dec. 30: Deadline to submit proposals for two Breast Cancer Coalition research grants, one a maximum of $25,000 for pre- and post-doctoral trainee/fellows and the other $50,000 for faculty applicants. Click here for the full RFP.