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fluidigm The Fluidigm C1 Single-Cell AutoPrep system, at left, will enable the Genomics Research Center to capture single cells in nanoliter volumes and prepare them for sequencing in the center's HiSeq2500 high throughput sequencing system (shown at right).

New system enhances GRC's single cell sequencing capabilities

The recent acquisition of a Fluidigm C1 Single-Cell AutoPrep system by the University's Genomics Research Center will greatly improve the center's single cell sequencing capabilities.

This enhanced capability will be of significant benefit for University researchers studying leukemia and other cancers, stem cells, or any human or mammalian biology involving responses in a small subset of cells, says John M. Ashton, PHD, the GRC's Associate Director. "We're hopeful that [this technology] will allow researchers the ability to ask questions they couldn't before."

The key advantage of the Fluidigm system is that it will enable the GRC to capture single cells and prepare them for sequencing in "very, very small volumes," Ashton explained. "It's been well documented that one of the more challenging hurdles of generating high quality data from single cells is the reaction volume. The reduced volume increases the chance of capturing the small amount of nucleic acid material by increasing the reagents' contact with nucleic acid. The Fluidigm platform allows us to perform the necessary chemical reactions in nanoliter volumes versus microliter volumes. The technology is evolving rapidly, where soon investigators will be able to use a new microfluidic chip that increases the number of cells that can be assayed at one time from 96 to approximately 820."

Combined with recent upgrades in the center's HiSeq2500 high-throughput sequencing system, the C1 will enhance the GRC's ability to "interrogate the transcriptome (genome) of complex cellular populations at single cell resolution," Ashton said.

Specifically, the new C1 platform will allow investigators to:

1. Determine gene expression profiles of phenotypically defined subpopulations of cells to give insight into heterogenetic responses.
2. Investigate clonality and clonal evolution of various cancer types.
3. Identify and monitor expression profiles unique to stem cells and their progeny.

"This is particularly important to leukemia research, which is thought to be stem cell driven," Ashton said. "We know, for example, that certain drugs kill the bulk tumor, but that's not getting at the root cause of the disease. We need to understand how those (stem) cells are alerted in response to a drug challenge, or whether a drug targets those populations or not. This system will help us begin to ask these critical questions."

The NIH Shared Instrumentation Grant that funded acquisition of the Fluidigm system resulted from collaboration between the GRC and several Medical Center investigators, Ashton said.

For the last five years, the center has generated custom workflows in single cell genomics that "worked to some extent," Ashton said. "One of the biggest flaws has always been lack of capability to perform high resolution capture of cells. That's what Fluidigm offers. We believe purchase of the Fluidigm C1 provides a significant strategic investment in single-cell genomics here at the University."

To learn more about the Genomic Research Center's services, contact Ashton.

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Does data entry interrupt communication in the exam room?

You walk into an exam room, nervous about your new diagnosis and eager to ask about the new medications you are about to start taking. Your clinician enters the room, exchanges greetings, then turns immediately to a computer to log into your electronic medical health record. Your caregiver next asks about recent symptoms, then again turns to the computer again to type in your responses. You have many questions but you wonder if your caregiver is actually listening, or is more worried about accurately documenting responses on the computer.

Josef Bartels, a medical and public health student at the School of Medicine and Dentistry, described this scenario at the University's recent Falling Walls competition. He wanted to illustrate that, despite all the advantages of electronic health records — accurate information at physicians' and patients' fingertips; quicker and more accurate prescribing; better management of increasingly complex patient information — there is a potential pitfall when it interrupts the communication that is essential to a good patient/physician relationship.

Bartels became interested in the topic when he examined periods of silence (>2 seconds) that occurred during conversations between 124 advanced cancer patients and their oncologists in and around Rochester, NY, and Sacramento, CA. By listening to audio recordings of the conversations, his team analyzed 1,211 such silences. Seeking to better understand the contexts and functions of silence in medical conversation, Bartels was surprised by the fact that fully 47 percent of the silences seemed to be associated with entering or accessing data on an exam room computer, where the clicking of a mouse or the clatter of a computer keyboard could be heard in the background.

"This doesn't mean data entry shouldn't be done or doesn't contribute to the care of patients," Bartels added, "but it does raise questions about what the physician's role is, and how to balance data management with relationship building and communication tasks central to patient-centered care."

Would it make more sense, for example, to have another person in the room to do the electronic data recording, so the physician could spend more time listening to and responding to the patient? Much as a pilot and co-pilot split up the duties of flying a plane and communicating with air traffic controllers?

Before suggesting solutions, Bartels emphasized the need to understand if these silences are a problem, if they create a disruption in conversation, and further, if those disruptions negatively impact communication. Often they didn't seem to; but occasionally they completely derailed the conversation.

Bartels noted what seemed to be a dose-response relationship. As the frequency and extent of computer associated silences increased, the frequency and extent of supportive conversation decreased. This will be explored further in future work to see if this trend is confirmed in a larger sample and more rigorous classification of computer-associated silences.

(Next: Some silences indicated a deep sense of connection between patient and physician.)

Introducing a new faculty member

Ellen Matson has joined the Department of Chemistry as an assistant professor. Research in the Matson group focuses on probing cooperative reactivity between non-traditional ligand platforms and first-row transition metals, specifically their ability to facilitate chemical transformations of industrial, environmental and biological significance. Matson comes to the University from the University of Illinois at Urbana-Champaign, where she did postdoctoral research in first-row transition metal complexes with Professor Alison R. Fout. She completed her Ph.D. at Purdue University (2013) with Professor Suzanne C. Bart as her adviser. Matson's thesis is entitled: "Synthesis of Low-Valent Uranium Alkyl Complexes: Exploring the Reactivity of the Uranium Carbon Bond for the Activation of Small Molecules."

Congratulations to . . .

Erika Snow and Leigh Sundem, who started July 1 as new trainees with the Clinical and Translational Science Institute (CTSI) Year Out Program for Medical Students. The program provides a year of mentored experience in clinical or translational research; trainees receive stipends and support to complete a Master's Degree program if desired. Snow is working with Scott McIntosh, Associate Professor of Public Health Sciences, on "The Role of E-cigarettes as a Barrier to Smoking Cessation." Sundem is working with John Elfar, Associate Professor of Orthopaedics, on "Erythropoietin for Compression Neuropathy: Preclinical Efficacy and Cellular Site of Action."

University research in the news

Efforts to improve health care for older adults in Rochester and the Finger Lakes region will be bolstered by a $2.5 million federal grant awarded to the Division of Geriatrics and Aging to establish an education center. "This is an unprecedented opportunity for our region to support the development of a health care workforce with the unique skills needed to care for an aging population," said Thomas Caprio, Associate Professor of Medicine and project director for the Geriatric Workforce Enhancement Program. The program supports the development of a health care workforce that integrates geriatrics with primary care, maximizes patient and family engagement, and transforms the healthcare system. Read more . . .

Researchers at the Wilmot Cancer Institute have developed what they believe is the first mouse model for investigating why a certain subset of acute myeloid leukemia (AML) patients responds particularly poorly to chemotherapy. Approximately 15 percent of AML patients harbor a mutation in the RUNX1 gene, and in these patients, standard treatment is unable to eradicate leukemic cells from their bone marrow, where the cancer is rooted. Scientists do not fully understand the underlying mechanisms protecting these residual AML cells. An article published recently in PLOS ONE by corresponding author Jason H. Mendler, Assistant Professor of Oncology, suggests that a genetically defined mouse model of RUNX1-mutated AML, developed at Wilmot, is the ideal platform to investigate the cellular mechanisms protecting residual AML cells in this molecular subtype of the disease. "Like all cancers, leukemia is not a one-size-fits-all, and therefore it's important to find better ways to study high-risk subtypes of the disease," said Mendler. "We believe our mouse model will allow us to quickly define new ways to target this challenging disease." Read more . . .

"Direct-to-consumer genetic testing, when paired with telemedicine, has the potential to involve more people in clinical research and accelerate the process of identifying the genetic causes and variations in chronic diseases such as Parkinson's," says Ray Dorsey, Professor of Neurology and lead author of a pilot study reported recently in Digital Health. Researchers at the University of Rochester and Johns Hopkins University partnered with 23andMe, a personal genomics and biotechnology company based in California, to determine if individuals with known genetic risk factors for Parkinson's disease could be diagnosed for the condition via telemedicine. The researchers also wanted to test the feasibility of conducting clinical research remotely. Working with 23andMe and the Michael J. Fox Foundation for Parkinson's Research, the researchers recruited 50 individuals in 23 states who agreed to undergo a remote assessment consisting of cognitive and motor tests via secure video conferencing. The participants also completed a survey. The study found that physicians at a single site were able to successfully and rapidly diagnose and categorize patients located across the country. Read more . . .

Phd dissertation defense

Katie Lannan, Microbiology & Immunology, "Discovery of New Molecules that Regulate Platelet Function." 1 p.m., July 28, 2015, K-307 (3-6408). Advisor: Richard Phipps.

Mark your calendar

July 31: NIF: An Unexpected Journey or Lessons Learned to Secure Projects of Scale (National Ignition Facility @ LLNL — A Case Study), by E. Michael Campbell, Senior Scientist at the Laboratory for Laser Energetics. 9:30-10:30 a.m., LLE Coliseum, 250 East River Road. RSVP by July 29 to Kelly Smith at or (585) 275-6049.

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.