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cd This image, captured with the multiphoton microscope, shows flu specific CD8+ T cells in green, blood vessels in red, in the trachea of an influenza mouse model.

Multiphoton microscope reveals immune response to influenza

When influenza strikes, killer T cells comprise "one of the critical populations" of white blood cells that help your body fight the infection — not by attacking the virus itself, but by attacking and destroying the cells that the virus has infected, explains Emma Reilly, a postdoctoral associate in the lab of David Topham, Professor of Microbiology and Immunology.

To do this, the cells must enter the infected respiratory tract and migrate through the tissue to locate the infected cells that line the airway (epithelium). How quickly does this occur? What is the mechanism by which these cells move through the tissue? Moreover, what signals are required to retain a population of these killer (CD8+) T cells as sentinel "memory" cells even after the infection is cleared, to prevent and limit future infections?

The multiphoton microscope housed in the Medical Center's Multiphoton Core Facility is helping Reilly and Technical Associate Kris Lambert pursue these questions. It allows them to capture 3D images of CD8+ T cells, literally as they move through the trachea of mice previously infected with influenza virus.

"One aspect of the project I'm interested in is not only understanding how the CD8+ cells move, but what is required for them to then stay in the tissue (after the infection), and where they need to go for that to happen," Reilly said. "If we could promote recruitment of these memory cells, that would be beneficial for longer lasting immunity."

Topham's lab has shown that "optimal CD8+ T cell mediated immunity" to more than one strain of flu virus (a.k.a. universal immunity) is provided when the T cells are retained in the lung tissue and airways, by interacting with collagen (the main structural protein of tissue) via the VLA-1 collagen receptor.

One hypothesis the lab is investigating is that extracellular matrix proteins found in the basement membrane of the respiratory epithelium are actively remodeled during and after an influenza virus infection, and that this regulates the migration of CD8+ T cells in the tissue and the formation of tissue memory. Live time-lapse imaging obtained from the Multiphoton Core as well as other imaging and molecular techniques will be used to further address these questions.

Training on microscope enables data collection throughout

Linda Callahan, Technical Director of the Multiphoton Core Facility, and her staff — Technical Associate Maria Jepson and Senior Technical Associate Paivi Jordan — provide training, starting with a review of each experiment's design to understand exactly what type of images are needed and the image analysis required to address the research question.

The MP core is also supported by Edward Brown, whose role as Scientific Director is to offer expertise in multiphoton microscopy for both experimental design and modifications to multiphoton experiments as they progress, and Seth Perry, who serves as a Multiphoton Advisor to researchers for multiphoton equipment customization, experimental design, and image analysis.

To maximize efficiency, Callahan and her staff "drive" the microscope at the start of the training process while trainees look on, then switch places later, so that data can be collected throughout the training.

"The learning program is geared to get people up to proficiency no matter how quickly they learn or what their previous experience in microscopy has been. The goal is for the investigator learning to use the microscope to learn at their own pace while still obtaining data for the PI's research program," Callahan added.

Files of images are stored on the protected University SMDNAS server. Researchers can then download the files to store in their own labs, as required by NIH. "Part of our education is to help investigators become aware of — and stay compliant with — what they need to do to meet NIH requirements," Callahan said.

Investigators use the multiphoton facility, on average, 30 hours a week — which by NIH standards is considered moderate usage of the instrument, says Callahan. "We work quite hard to make sure everyone gets on the microscope when they need to; we are operating under a directive to keep all investigators who need multiphoton research moving forward, and our training program enables users to proficiently use the microscope after hours," Callahan said.

A modest hourly fee is charged. Callahan is on call 24/7 for after hours users. To learn more, contact Callahan.

(The Multiphoton Research Core is one of six facilities that make up the Medical Center's Shared Resource Laboratories, and one of 22 of the Shared Resource or Cost Center facilities offered by the Medical Center.)

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

UR student curates largest North American festival devoted to Japanese film

At this year's Japan Cuts, the largest North American festival of new experimental, documentary and popular films from that country, a University of Rochester PhD student in Visual and Cultural Studies will introduce the films and moderate interviews with cinematic stars and filmmakers.

This is the second year that Joel Neville Anderson has served as curator of Japan Cuts, which runs through July 19 at Japan Society in Manhattan. This year's festival presents 28 feature films, dozens of experimental shorts, and appearances by 17 special guests — actors and filmmakers, for example — from Japan, the U.S., and Liberia.

For Anderson and his close collaborators at Japan Society, Japan Cuts is the culmination of a year-round, behind-the-scenes process of reviewing and choosing films, working with film distributors, and preparing background material. Anderson says this is an extension of the research he does here — and is an important step in shaping a career that he hopes will combine academic research and teaching with outreach to audiences outside academia.

Click here to learn more about Anderson and his involvement in Japan Cuts.

UR Ventures newsletter explores innovation and technology commercialization

UR Ventures Technology Review is the recently launched newsletter of the UR Ventures office that helps University researchers apply for patents and license their innovations. The first issue looks at:

1. Community Forensic Interventions, a Rochester start up formed by Steven Lamberti, Professor of Psychiatry, and Robert L. Weisman, Associate Professor of Psychiatry, to promote safe and effective community care for justice-involved adults with serious mental illness.

2. A promising technology develped by Minsoo Kim, Associate Professor of Microbiology and Immunology, that uses light to concentrate cancer-targeting T-cells at the site of a tumor while reducing undesirable side effects.

3. An overview of the University's commitment to Data Science.

You can read the newsletter and/or subscribe by clicking here.

Funding from Knights Templar supports study of Batten disease

Ruchira Singh, Assistant Professor of Ophthalmology and Biomedical Genetics, will use a grant from the Knights Templar Eye Foundation to create a human model of Batten disease (CNL3) using patient's own cells to investigate how this neurodegenative disease causes blindness.

The project may lead to not only a better understanding of the disease's mechanisms, but also aid in the development of drug therapies to preserve vision in affected patients.

Batten disease is a rare neurodegenerative syndrome that erupts with little warning. It first steals sight, then cripples cognitive and motor capacities, and while different variations of the disease bring different ages of onset and rates of progression, it is, ultimately, fatal. The most common form is juvenile Batten disease, with symptoms beginning between the ages of 5 and 8. Read more . . .

Grant will support education of post docs who are deaf or hard of hearing

A nearly $4 million grant to educate post-doctoral students who are deaf or hard-of-hearing expands an ongoing relationship between the University, Rochester Institute of Technology and RIT's National Technical Institute for the Deaf. Two years ago the local institutions partnered to build a similar program for graduate students, facilitating the transition from master's degree programs offered at RIT to Ph.D. programs at the University of Rochester. The latest grant allows the University and RIT/NTID to develop a three-year mentored, post-doctoral research experience.

The goal is to create a program that would serve as a national model to prepare deaf and hard-of-hearing scholars for careers in the biomedical and behavioral sciences.

"At the end of the program, the deaf and hard-of-hearing professionals who participate will be well-prepared to step into an academic career in the biomedical sciences," said Stephen Dewhurst, principal investigator and Vice Dean for Research at the School of Medicine and Dentistry. Read more . . .

Congratulations to . . .

Ronald M. Epstein, Professor of Family Medicine, whose 2002 article, "Defining and Assessing Professional Competence," is among the top-five most widely cited medical education articles in the last century. Three other manuscripts either authored or co-authored by Epstein are ranked in the top 50, according to The Association of American Medical Colleges and its journal, Academic Medicine. Epstein's most-cited review article expressed the need to revamp the definition of "professional competence" for physicians, by expanding it beyond core knowledge of medicine and basic skills to include reasoning, judgment, management of ambiguity, professionalism, time-management and communication skills, and teamwork, for example. Read more . . .

Robert Poreda, Professor of Earth and Environmental Sciences, who has been elected a Fellow of the Geological Society of America, and will be recognized with other newly elected fellows Nov. 1 at the GSA 2015 Annual Meeting Presidential Address & Awards Ceremony in Baltimore. Poreda was nominated as GSA Fellow for his research contributions on application of noble gases toward understanding the history of mantle dynamics, use of tritium-helium groundwater dating, 21Ne cosmogenic surface exposure age dating techniques, and environmental impacts of unconventional energy development on groundwater."

Jonathan W. Mink, the Frederick A. Horner, M.D. Endowed Professor in Pediatric Neurology and Chief of the Division of Child Neurology at Golisano Children's Hospital, who has received the first Dr. Oliver Sacks Award for Excellence in Tourette Syndrome. The award, presented by the Tourette Association of America, was announced at the First World Congress on Tourette Syndrome and Tic Disorders in London. Mink is a national leader in the field of pediatric movement disorders. He led the development of the first guidelines for use of Deep Brain Stimulation in treating adults with Tourette Syndrome that is resistant to other treatment, and developed a model for how brain circuits malfunction in patients with the disease. He has been involved with the Tourette Association of America since 1996, and has acted as a mentor to many young scientists and clinicians who have devoted their careers to Tourette Syndrome. In addition to Tourette Syndrome, Mink treats patients with dystonia, chorea, tics, myoclonus, parkinsonism, and other movement disorders. He also leads the Batten Disease Diagnostic and Clinical Research Center, the largest clinical research group for Batten Disease in the country.

University research in the news

"A raft of new discoveries on Smiths Island have helped archaeologists paint a clearer picture of what life was like for Bermuda's earliest settlers," the Royal Gazette of Bermuda reported recently in a story about Michael Jarvis, Associate Professor of History, and his team who continued their archaeological project on the island this summer with excavations at the Oven Site, Cave Site and Small Pox Bay. Click here for a Research Connections series on the project last fall.

The goal for many cancer patients is to reach the five-year, disease-free mark, but new research from the Wilmot Cancer Institute suggests that two years might be a more practical survival goal for people with follicular lymphoma. About 20 percent of follicular lymphoma patients consistently experience their disease coming back within two years of being treated with the latest therapies — despite the fact that most follicular lymphoma patients can expect to live 20 years. People who relapse early may have a disease with distinctly different biology, said Carla Casulo, a Wilmot oncologist and Assistant Professor of Medicine, who led the study. The findings are published online by the Journal of Clinical Oncology and will be accompanied by an editorial in JCO's print edition later this summer. Read more . . .

PhD dissertation defenses

Lingxiang Xiang, Computer Science, "Compiler Assisted Speculation for Multithreaded Systems." 2 p.m., July 6, 2015, CSB 703. Advisor: Michael Scott.

Jenna Frame, Pathology, "Emergence and Regulation of Hemogenic Endothelium in the Mammalian Yolk Sac. " 9 a.m., July 7, 2015, K-307 Auditorium. Advisor: James Palis.

Supriya Ravichandran, Biomedical Engineering, "Discovery and Characterization of Antibodies that Bind Nanoparticles." 10 a.m., July 14, 2015, K-307. Advisor: Lisa DeLouise.

Dhara Trivedi, Physics, "Dynamics of Photoexcited State of Semiconductor Quantum Dots." 1:30 p.m., July 17, 2015, Bausch and Lomb 372. Advisor: Oleg Prezhdo.

Nicole Paris, Genetics, "Role of Wilms Tumor 1 and β-Catenin in Embryonic Diaphragm Development." 9 a.m., July 17, 2015, Ryan Case Method Room (1-9576). Advisor: Kate Ackerman.

Lesley Chapman, Translational Biomedical Science, "MicroRNA-451 regulates T helper cell responses." 2 p.m., July 22, 2015, Helen Wood Hall Auditorium (1W-304). Advisor: Craig Morrell.

Adam Bosen, Biomedical Engineering, "Visual Capture and Recalibration of Auditory Spatial Perception." 9 a.m., July 27, 2015, Med Center K-307. Advisor: Gary Paige.

Steven Hunzicker, Electrical Engineering, "Quantitative Vascular Elastography: Stiffness and Stress Estimation for Identifying Rupture-Prone Plaques." 1 p.m., July 29, 2015, Computer Studies Building, Room 426. Advisor: Marvin Doyley.

Youssef Farhat, Biomedical Engineering, "Identification of PAI-1 as a Biological Target for the Promotion of Scarless Flexor Tendon Healing." 9 a.m., July 30, 2015, K-307 (Med 3-6408). Advisor: Hani Awad.

Mark your calendar

July 13: "How to write like a Biologist: using rhetorical genre analysis to help students understand disciplinary specialization and how it affects writing choices within the research article," Department of Biology Donut Talk by Katherine Schaefer, Lecturer and Specialist in Scientific and Technical Writing, College Writing Program. Noon to 1 p.m., Hutchison 473.

Aug. 3: Applications due for the Fulbright U.S. Scholar Program, which provides approximately 800 teaching and/or research grants to U.S. faculty and experienced professionals in a wide variety of academic and professional fields. Click here to view a University of Rochester workshop on the program. Questions? Contact Apply directly to the Fulbright program.

Aug. 3: Deadline for AS&E PumpPrimerII awards, which are designed to help innovative, high-risk projects develop proof of concept and/or pilot data in order to secure extramural funding. Arts and Sciences faculty can learn more from Debra Haring; Engineering faculty should contact Cynthia Gary.

Aug. 5: Free workshop on how to apply for Horizon 2020 research funding from the European Union. 8:30 a.m. to noon at the Washington Hilton Hotel, Washington D.C. Sponsored by BILAT USA 2.0. Registration is required 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.

Copyright 2013, All rights reserved.
Rochester Connections is a weekly e-newsletter for all faculty, scientists, post docs and graduate students engaged in research at the University of Rochester. You are receiving this e-newsletter because you are a member of the Rochester community with an interest in research topics.