Research Connections :: University of Rochester

This bull's eye assay from the lab of Luis Martinez-Sobrido, Associate Professor of Microbiology and Immunology, shows how the movement of influenza viruses can be tracked when a fluorescent dynamic Timer protein is fused to the virus. The Timer protein shifts color from green to red over time, hence the predominance of red at the center of this plaque of infected cells, where the earliest infected cells reside. Recently infected cells, showing green, predominate at the periphery.

Spread of influenza A and B viruses can be tracked from cell to cell with fluorescent dynamic Timer protein

The lab of Luis Martinez-Sobrido, Associate Professor of Microbiology and Immunology, has demonstrated how the movement of Influenza A and B viruses can be tracked from cell to cell, both in vitro and in vivo, when a dynamic fluorescent protein Timer, which has the unique characteristic of shifting color from green to red over time, is fused to a viral protein.

This gives researchers a valuable tool to not only identify influenza infected cells, but also determine the approximate chronology by which they became infected, Martinez-Sobrido's team reported in PlosOne. This ability to do real-time modeling of influenza virus replication and infection "represents an important advantage over previous static-fluorescent protein influenza viruses that cannot be used to determine the duration of cellular infection," they add.

This research was funded by a 2014 University Research Award to Martinez-Sobrido.

Influenza A and B viruses are an important cause of death in humans. In 2013 alone, they claimed an estimated 3,700 lives in the United States, and upwards of 500,000 worldwide. In addition, influenza A viruses caused at least three 20th century pandemics, including the so-called Spanish Flu of 1918 that claimed between 30 and 50 million lives. The first influenza A virus pandemic of the 21st century, in 2009, is estimated to have caused at least 200,000 deaths worldwide.

In the paper, Martinez-Sobrido's team describes how it generated replicating influenza A and B viruses where the viruses' non-structural protein 1 (NS1) was fused to the dynamic Timer fluorescent protein. The engineered viruses displayed similar characteristics to wild-type viruses in tissue culture, where the spectral shift of the engineered influenza viruses from green to red allowed the researchers to measure the rate and cell-to-cell spread of infection using fluorescent microscopy, plate readers or flow cytometry.

They were also able to show that Influenza A viruses modified to express the Timer protein were "useful" in evaluating the dynamics of viral infection in mouse lungs using an in vivo imaging system.

"This could be of particular use to evaluate the changes in host gene expression at different stages of viral infection, because we are able to identify cells with a recent infection (green) and cells with a sustained infection (red)," the researchers write. "This could lead to the identification and characterization of genes expressed during varying stages of influenza viral infection and the time required for the activation of host restriction factors . . . "

Ultimately, this could lead to a better understanding of influenza virus pathogenesis as well as the development of more effective drug treatments against influenza viral infections.

Michael Breen, an undergraduate student in Martinez-Sobrido's lab who was funded with a Rochester Academy of Science Student Grant, is lead author of the study. In addition to Martinez-Sobrido, co-authors are Aitor Nogales, a postdoctoral fellow in the lab; former graduate student Steven Baker, who was funded by the University of Rochester Immunology Training Grant and is now a postdoctoral fellow at the University of Wisconsin-Madison, and Daniel Perez, an influenza researcher at the University of Georgia College of Veterinary Medicine.

Click here to read the study in full.

About University Research Awards

Originally called Provost's Multidisciplinary Awards, the University Research Awards go to recipients who demonstrate their projects favor new research with a high probability of being leveraged by future external funding.

Applications are sought from faculty across the University.

Read more here.

Do you have an interesting photo or other image that helps illustrate your research? We would like to showcase it. Send a high resolution jpg or other version, along with a description of what it shows, to bmarcotte@ur.rochester.edu.

PI oversight of human subject protection: Why it matters

(This is the first in a series of articles to help principal investigators understand their role in ensuring that human subject protection requirements are met in their studies.)

You're a principal investigator at the University of Rochester.

You've got a growing caseload of patients to look after, or increasing numbers of students in your classes. You've just been asked to form a research center or take on other leadership responsibilities. You've got papers to write, grant applications to file.

And now, with approval of your research project involving human subjects, you've got Research Subject Review Board scrutiny and a host of federal regulations — things you never learned about in graduate school — to worry about as well.

Is it really that big of a deal if one or more of your human subjects signed a consent form that was two months out of date?

Absolutely. This is an example of noncompliance with human subject regulations that — if repeated or not addressed — could invalidate your project's findings, be reported to your funding agency, even jeopardize your standing with the University.

And yet it's the kind of noncompliance that can all too easily occur when "multiple pressures on PIs result in a lack of attention to what is happening on the ground in their research programs," says Steven Lamberti, a Professor of Psychiatry who has felt those pressures as a PI himself.

That's why Lamberti, who chairs the University's Research Subject Review Board for behavioral and social sciences, recently joined Kelly Unsworth, Director of Research Education and Training with the University's Office for Human Subject Protection, in co-presenting a PI Oversight training session to help principal investigators understand that they are ultimately responsible for ensuring that human subject protections are adhered to in their projects.

However, this does not have to be the overwhelming responsibility that it might first appear to be, if PIs:

1. familiarize themselves with their responsibilities (spelled out here and also linked in all RSRB approval letters)
2. make sure study team members are properly trained for their tasks and;
3. closely communicate with members of their study team.

"Certainly PIs can't do every possible task in a study," Unsworth noted. "But we don't want to have a study get approved and have the sole responsibility for the conduct of that research fall into the lap of the study coordinator or the resident. We want to give PIs the tools, and have them think about ways they can better manage their oversight responsibilities."

"You don't have to memorize the federal regulations," adds Lamberti. "You do have to pay attention to what happens in your lab." Indeed, he says, PI's could eliminate "perhaps two-thirds to three-quarters of all non-compliances" simply by checking to make sure three relatively straightforward tasks are done properly: obtaining informed consent; submitting annual progress reports; and maintaining — either electronically or in a file cabinet — a regulatory file of all the paperwork associated with their studies.

In this series, Unsworth and Lamberti will share their tips and point out resources that can help PI's make sure human subject protection safeguards are strictly adhered to in their studies. Next: some pitfalls to avoid in obtaining informed consent.

Questions? Call the Office for Human Subject Protection at 273-4127.

Symposium addresses challenges of conserving cultural heritage monuments

Researchers from the U.S., Singapore, Ghana and Italy will give talks at "Analysis and Conservation of Cultural Heritage Monuments: Challenges and Approaches Across Disciplines," a symposium to be held from 3 to 6:30 p.m., March 30, in the Wells-Brown Room of Rush-Rhees Library. The symposium is free and open to the public.

The speakers and their topics are:

1. Michael Walsh, Nanyang Technological University: "Conflict and Culture in Cyprus: A Heritage Project in an Unrecognized State."
2. Renato Perucchio, Professor of Mechanical Engineering and Director of the Archaeology, Technology, and Historical Structures Program: "Engineering Digital Models of Complex Heritage Monuments."
3. Christopher DeCorse, University of Syracuse: "A Disappearing Past: Development, Archaeology, and Cultural Resource Management in Post-Conflict Sierra Leone."
4. Paolo Vitti, University Roma 3: "Preserving Identity through Cultural Heritage: the Restoration of the Armenian Church in Nicosia, Cyprus."
5. Michael Jarvis, Associate Professor of History: "Digital Archaeology and Historic Visualizations: Case Studies from Bermuda and Ghana."
6. William Gblerkpor, University of Ghana: "Conserving a Cultural Fortress: Krobo Mountain, Ghana."

In addition, Vitti will give a free lecture, open to the public, on "Mausoleum of the Hadrian Rediscovered: Architecture, Function and Symbolism," 7:30 p.m., March 31 at the Memorial Art Gallery.

The symposium, made possible by the Selwyn Endowment Fund, is co-sponsored by Nanyang Technological University, the University of Rochester and the University of Ghana.

For more information visit the symposium website.

New model could help determine age of stars more precisely

A model developed by Eric Blackman, Professor of Physics and Astronomy, and James E. Owen helps explain how the rotation of stars, their emission of x-rays, and the intensity of their stellar winds vary with time. According to Blackman, the work could also "ultimately help to determine the age of stars more precisely than is currently possible."

In a paper published this week in Monthly Notices of the Royal Astronomical Society, first author Blackman and Owen, a NASA Hubble fellow at the Institute for Advanced Study, Princeton, describe how they have corroborated known, observable data for the activity of Sun-like stars with fundamental astrophysics theory. By looking at the physics behind the speeding up or slowing down of a star's rotation, its x-ray activity, and magnetic field generation, Blackman says the research is a "first attempt to build a comprehensive model for the activity evolution of these stars." Read more . . .

Book focuses on the role of district central offices in turning around struggling K-12 schools

Kara Finnigan, Associate Professor of Educational Policy at the Warner School, and Alan Daly, Professor and Chair of Education Studies at the University of California-San Diego, have co-edited a book about the important role of central district offices in turning around the nation's lowest performing K-12 schools.

Thinking and Acting Systemically: Improving School Districts Under Pressure (available next month from American Educational Research Association) comes as federal high-stakes accountability policies and programs, such as No Child Left Behind and Race to the Top, have had limited success at the school level over the last decade.

"System-wide approaches to improvement under pressure have received inadequate coverage in policy-related discussion about low academic performance, which we argue is a missed opportunity to improve educational opportunities and outcomes for youth in our public education system at scale," Finnigan and Daly explain in their introduction.

Finnigan, Daly, and the book contributors argue for:

1. The need to pay greater attention to building the capacity of leaders within districts, given the shifting instructional, curricular, and socio-emotional needs in school systems.
2. Policies that focus on skill development, recognize and support performance, create opportunities for collaboration, build leader capacity, and create networks of knowledge sharing. These policies hold potential for improving districts, but will require a paradigm shift in the way society views the public school system and those who work within it—one that moves away from blame and toward complex systems change.

Read more here.

New funding program fosters collaborations among CTSA hubs

The Collaborative Innovation Award Program enables innovative collaborations among researchers at the various Clinical and Translational Science Award hubs — including our own Clinical and Translational Science Institute — to overcome system-wide barriers to translating initial discoveries into patient care.

"The goal is for the CTSA network to really function like an integrated network – not as a bunch of institutions doing their own thing," explains Martin Zand, Co-director of the University's CTSI in a Q&A at the CTSI Stories blog.

A wide range of topics could be funded, such as educating people to become research coordinators to combat the current labor shortage in clinical and translational research, or aiding research volunteer enrollment.

Anyone who would like more information about these awards should contact Carrie Dykes, CTSI Research Engagement Specialist.

University researchers in the news . . .

Jill Halterman, Professor of Pediatrics, has received a $3.6 million grant from the National Institutes of Health to research a preventive asthma intervention that will help connect pediatric asthma patients to primary care providers for follow-up after an emergency room visit. "Asthma is the most common reason for a pediatric emergency visit," said Halterman. "But many of these patients don't end up getting the preventive medication they need after being discharged, and they wind up back in the emergency department again a month later." Scheduling follow-ups via telemedicine will help to solve this problem. Using a network that the Department of Pediatrics has established with the Rochester City School District, children who have been referred after an emergency room visit can be seen during the school day, in the school health office, by a pediatric provider working remotely. This allows their caregivers to return to work, if needed, with communication with the provider occurring via teleconference or telephone. Read more . . .

A Parkinson's iPhone app developed by Sage Bionetworks and University neurologists Ray Dorsey and Karl Kieburtz was highlighted by Apple this week during its semi-annual product launch event. The mPower app gathers real time data from Parkinson's patients in an effort to more fully understand the disease and how it impacts daily life. The app also allows patients to track symptoms and how treatments are impacting the progression of the disease. For example, the app can measure the severity of the disease by analyzing the subtle changes in the voice of Parkinson's patients. In addition, the app uses other iPhone functions — such as the touch screen, motion sensors, and GPS — to measure dexterity, balance and gait, and memory multiple times per day. Read more . . .

Nabil Hossain, a PhD student in the computer science group led by Henry Kautz, the Robin and Tim Wentworth Director of the Goergen Institute for Data Science, and Hossain's collaborators have trained a machine-learning algorithm to "spot tweets that relate to alcohol and those sent by people drinking alcohol at the time," according to MIT Technology Review. They have also found way to "find a Twitter user's home location with much greater accuracy than has ever been possible and therefore to determine whether they are drinking at home or not." This can help researchers "better understand the occurrence, frequency, and settings of alcohol consumption, a health-risk behavior, and can lead to actionable information in prevention and public health." Read more . . .

Since November, a team of University and Adobe researchers has been outperforming other approaches to creating computer-generated image captions in an international competition called the Microsoft COCO Image Captioning Challenge. The key to their winning approach? Thinking about words — what they mean and how they fit in a sentence structure — just as much as thinking about the image itself. The Rochester/Adobe model mixes the two approaches that are often used in image captioning: the "top-down" approach, which starts from the "gist" of the image and then converts it into words, and the "bottom-up" approach, which first assigns words to different aspects of the image and then combines them together to form a sentence. The team includes Jiebo Luo, Associate Professor of Computer Science; doctoral student Quanzeng You; and their Adobe collaborators, Hailin Jin, Zhaowen Wang, and Chen Fang. Read more . . .

A Q and A with David Goldfarb, Professor of Biology, describes why yeast is such a good research specimen. Yeast was at the center of one of Goldfarb's patents, titled "Method for altering the lifespan of eukaryotic organisms," which Reuters determined to be "the most-cited discovery to emerge from academic research in recent years." Hear a podcast and read more here . . .

A team of researchers led by Julie Fudge, Associate Professor of Neuroscience, shows that our brains may be hardwired to become sensitive to stressful environments at an early age and, if overstimulated, this may contribute to anxiety disorders and even psychotic syndromes later in life. The study, which appears in the journal Brain Structure and Function, focuses on two structures deep in the brain. The central nucleus of the amygdala (Ce) is thought to be involved in responses to immediate threats and stimulus, such as becoming startled or freezing in reaction to a loud noise. The bed nucleus of the stria terminalis (BST) is thought to be involved in regulating a person's state of vigilance, such as determining whether or not an environment or a situation poses a potential threat. While Ce and BST reside in different parts of the brain, the two areas are hardwired to each other by bundles of long distance axon fibers that enable the separate regions to communicate. The researchers found that the direction of the connection is essentially one way. The Ce — or immediate fear signaling center — conveys information to the BST, the structure that mediates general threat sensing or anxiety states. This arrangement suggests that repeated activation of the Ce by immediately fearful or traumatic events may shape long-term anxiety states in the BST.

Congratulations to . . .

Daniel Nikolov, a PhD student in Optics, for being selected for a Link Foundation Fellowship in Modeling, Simulation, and Training for the 2016-17 academic year. These $29,000 awards were created to foster advanced level research, to enable Ph.D. students the freedom to work on their research full time, and to disseminate the results of that research through conferences, journals, and other publications.

Autumn Gallegos, Senior Instructor of Psychiatry, and Caroline Quill, Assistant Professor of Medicine, who have been named 2016 Mentored Career Development Program (KL2) Scholars by the Clinical and Translational Science Institute. The goal of the program is to promote the successful transition of KL2 scholars to independent careers as clinical and translational investigators. Gallegos' project is "Effects of Mindfulness on PTSD: A Community-Based Clinical Trial among Trauma Survivors." Her mentors are Wilfred Pigeon, Kathi Heffner, and Catherine Cerulli. Quill's project is "Improving ICU Patient Outcomes Using Graph Isomorphism Analysis." Her mentors are Martin Zand, Scott Halpern, Anthony Pietropaoli.

PhD dissertation defenses

Emily Landeen, Biology, "Investigating the molecular genetic basis of the large X effect in Drosophila." Noon, March 28, 2016. Lander Auditorium. Advisor: Daven Presgraves.

Walter Knight, Pharmacology, "Regulation, Function, and Mechanisms of Cyclic Nucleotide Phosphodiesterase 1C in Pathological Cardiac Remodeling and Dysfunction." 1 p.m., March 29, 2016. Adolph Aud, 1-7619. Advisor: Chen Yan.

Andrew Law, Biomedical Engineering, "Brain-computer interface control with small motor cortex ensembles." 8:30 a.m., March 31, 2016. Goergen 101. Advisors: Marc Schieber and Greg Gdowski.

Rajarshi Chakraborty, Materials Science, "Resolving Puzzles in Conjugated Polymer Photophysics: Nanoseconds to Microseconds." 2 p.m., March 31, 2016. Gavett 208A. Advisor: Lewis Rothberg.

Alicia Guzman, Visual and Cultural Studies, "Connected in Isolation: Land and Landscape in New Mexico and the Greater Southwest." 10:30 a.m., April 1, 2016. Morey 524. Advisor: Janet Berlo.

Michael Skarlinski, Materials Science, "Advanced Molecular Dynamics Techniques for the Simulation of Nano-scale Mechanical and Electrochemical Properties." 1 p.m., April 6, 2016. Hopeman 224. Advisor: David Quesnel.

Mark your calendar

March 29: Network Science/Regulatory Science, presented by Martin Zand, Co-Director, Clinical and Translational Science Institute, and Scott Steele, Director, Government and Academic Research Alliances and Deputy Director, Goergen Institute for Data Science. Noon to 1 p.m. Helen Wood Hall Auditorium (1w-304). CTSI Seminar series.

March 30: Symposium: "Analysis and Conservation of Cultural Heritage Monuments: Challenges and Approaches Across Disciplines." 3 to 6:30 p.m., Wells-Brown Room of Rush-Rhees Library. Free and open to the public. For more information visit the symposium website.

March 31: "Seeing Stars: How Astronomy has enabled New Visions of the Living Eye," presented by Jesse Schallek, Assistant Professor of Ophthalmology, Neurobiology and Anatomy and the Center for Visual Science. Phelps Colloquium, 4-5:30 p.m., Meliora Grand Ballroom, Frederick Douglass Building. Register here by March 25.

April 1: Palliative Care, Hospice, and End-of-Life Options of Last Resort, presented by Timothy Quill, Professor of Medicine. Noon to 1 p.m., Helen Wood Hall Auditorium (1w-304). Public Health Grand Rounds.

April 7: Center for Emerging and Innovative Sciences (CEIS) 16th annual University Technology Showcase, 1 to 5 p.m., DoubleTree Hotel, 1111 Jefferson Road. An opportunity for university researchers to present their work to industry as well as other researchers and organizations that promote economic development. Register here by March 29.

April 7: "The Vulnerable Newborn Brain – Lessons from Neuroimaging," presented by the Department of Pediatrics 20th Gilbert B. Forbes Scholar, Donna M. Ferriero, the Marie Wattis Distinguished Professor & Chair, Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco. Noon, Helen Wood Hall Auditorium (1-w304).

April 8-10: RocHackHealth: Rochester Healthcare Data Hack-A-Thon. University faculty, students, staff and other "techies" form teams to collaborate on solutions to healthcare related data problems. Click here to see the schedule of events, to register or to find additional information.

April 15: Deadline to apply for the University's preliminary Falling Walls competition, which will select a graduate student, postdoc, junior faculty member or young entrepreneur to represent the University at the international Falling Walls competition in Berlin, Germany, this fall. Register at the official Falling Walls website; contact Adele Coelho, Faculty Outreach Coordinator, at adele.coelho@rochester.edu for additional information.

April 15-16: Hard Coded Humanities, a two-day interdisciplinary conference organized by the Andrew W. Mellon Fellows in Digital Humanities, will challenge traditional distinctions between software and hardware in scholarly contexts. All events are free to attend. Register to secure your spot in a workshop and to stay in the loop. More info can be found on the conference site.

April 21: 2nd Annual Rochester Global Health Symposium. 8:30 a.m. to 5:30 p.m., Saunders Research Building. The call for posters and registration portal are available here.

Please send suggestions and comments to Bob Marcotte. You can see back issues of Research Connections, an index of people and departments linked to those issues, and a chronological listing of PhD dissertation defenses since April 2014, by discipline.