In this edition of Research Connections, find links to researchers in the news, updates on important deadlines, and more news for University of Rochester researchers.
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Some strains of Drosophila melanogaster can tolerate high levels of ethanol; others can't. Prof. James Fry has pinpointed a specific gene mutation that helps account for this, lending support to the theory that at least some genetic variation within a species is beneficial, and is maintained by balancing selection. (Photo by André Karwath. Made available under the Creative Commons Attribution-Share Alike 2.5 Generic license.)

Study supports 'balancing selection' as an explanation for genetic variation within a species

Why is it that we can find so many genetic variations within a single species?

One theory in this longstanding debate among evolutionary biologists is that most of this genetic variation is 'junk,' caused by mutations that are of no value or could actually harm a species, and tend to be eliminated over the long term because they make it less likely for individuals with those mutations to reproduce. Much of the variation we see, in other words, is simply the result of mutations occurring faster than they can be eliminated from a population.

Another theory is that at least some of this genetic variation is maintained because it is beneficial. For example, a novel trait resulting from a mutation may help one subset of a population survive better in one type of environment, while other members of the same species that lack the trait thrive better in other environments. This and other mechanisms that can maintain variation go under the general term of balancing selection.

A new study by James Fry, Associate Professor of Biology, and Mahul Chakraborty, now a postdoctoral fellow at the University of California at Irvine, offers strong support for the balancing selection theory by examining how different strains of Drosophila melanogaster handle alcohol. The study appeared in the Jan. 25 issue of Current Biology.

"This model fruit fly species, used widely in the study of genetics, also lives outside of the lab," Fry said. "If you go to the orchards around Rochester in late August or September when the fruit is on the ground, you can find clouds of them breeding."

Previous studies have shown that some strains of D. melanogaster in the wild can feed and reproduce on fruit with high levels of ethanol — as much as five or six percent — which would kill other strains.

Acting on an educated hunch, Fry and Chakraborty decided to examine to what extent this differing ability to tolerate alcohol involves aldehyde dehydrogenase, an enzyme known to help detoxify ethanol in both flies and humans by converting a toxic ethanol byproduct called acetaldehyde into acetate, which is less toxic.

Fry and Chakraborty used DNA sequencing on D. melanogaster strains from around the world and found that different strains have different forms of the enzyme. Moreover, for this study, they pinpointed how variation in a single amino acid — among the 500 or so amino acids that constitute the enzyme's protein chain — helps determine to what extent a strain of fruit flies can, or cannot, tolerate high levels of ethanol.

The mutation in this "alcohol tolerance" gene, Fry noted, has been around for "thousands of generations of fruit flies, perhaps for 10,000 or 20,000 generations. That would be incompatible with the idea that it is a recent mutation on its way to being eliminated."

The mutation clearly gives certain strains of fruit flies a competitive edge over other strains in environments with high levels of dietary alcohol. But it places those strains at a disadvantage in environments where alcohol levels are lower. Why? The mutation reduces the ability of aldehyde dehydrogenase to carry out its other important function, namely eliminating toxic byproducts of oxidative damage that are produced in the fly's own cells. In low alcohol environments, this gives other strains the edge.

"Basically what we found is a classic hypothesized tradeoff in fitness between environments, which is the central assumption for any theory for maintenance of genetic variation by environmental differences," Fry said. "It doesn't prove the difference is maintained by balancing selection, but everything points to that as the explanation for this variant being there."

The study's "elegant findings provide concrete, elusive evidence supporting a foundational and controversial theory about the maintenance of genetic variation," write Andrew D. Gloss and Noah K. Whiteman, evolutionary biologists at the University of Arizona, in their discussion of the paper.

While studies of entire genomes now suggest balancing selection might be widespread, they note, few studies have identified variations in specific genes to support the theory, as Fry and Chakraborty do in this study.

"Leveraging modern genetic tools, including insertion of alternative alleles of this enzyme into the genomes of isogenic flies, coupled with enzymology and laboratory fitness studies, their study sets a new bar in the field."

Balancing selection may be at work in human populations as well, Fry said.

For example, classic studies in the 1950s showed that the trait responsible for sickle cell anemia also confers partial resistance to a virulent form of malaria in Africa. As a result, carriers and actual victims of sickle cell anemia "are much more common than you would expect based on the mutation rate alone," Fry said.

"Maybe that's the tip of the iceberg; maybe there are quite a few human traits that are affected by genes that have variation maintained by balancing selection. Possibly some traits that seem bad actually are there because, at least in the past, they conferred some advantage under certain circumstances, as opposed to being deleterious mutations that haven't been eliminated yet."

Click here to read the study by Fry and Chakraborty, entitled "Evidence that Environmental Heterogeneity Maintains a Detoxifying Enzyme Polymorphism in Drosophila melanogaster."

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UR research in action: App helps Las Vegas health department monitor restaurants for foodborne illnesses

An app developed by University computer scientists is helping the Las Vegas health department improve the city's inspection protocols, Aaron Dubrow writes in a National Science Foundation press release.

The app, called nEmesis, uses natural language processing and artificial intelligence to identify food poisoning-related tweets, connects the tweets to restaurants using geotagging and identifies likely hot spots. It was developed by Henry Kautz, the Robin and Tim Wentworth Director of the Goergen Institute for Data Science and Professor of Computer Science, and Adam Sadilek, a former PhD student here now working at Google Research. Sean Brennan, a graduate student, and Vincent Silenzio, Associate Professor of Psychiatry, were also part of the team that worked on nEmesis.

During a recent collaboration with the Las Vegas health department, half of the city's restaurant inspections were performed using the traditional random approach and half were done using nEmesis, without the inspectors knowing that any change had occurred in the system.

Analyzing the results of the experiment, the researchers found the tweet-based system led to citations for health violations in 15 percent of inspections, compared to 9 percent using the random system. Some of the inspections led to warnings; others resulted in closures.

The researchers estimate that these improvements to the efficacy of the inspections led to 9,000 fewer food poisoning incidents and 557 fewer hospitalizations in Las Vegas during the course of the study.

"nEmesis has proved to be a useful tool for quickly and accurately identifying facilities in need of support, education, or regulation by the health department," says Lauren DiPrete, senior environmental health specialist for the Southern Nevada Health District. Read more . . .

Conference challenges scholarly distinctions between software, hardware

Harded 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.

The April 15-16 conference will include keynotes by digital humanities scholars Matthew Kirschenbaum and Kari Kraus; workshops on physical computing, electronic literature, and video game music; and panels featuring an international roster of humanities researchers.

All events are free to attend. Please register to secure your spot in a workshop and to stay in the loop. More info can be found on the conference site.

CEIS Technology Showcase to be held April 7

The Center for Emerging and Innovative Sciences (CEIS) is hosting its 16th annual University Technology Showcase from 1 to 5 p.m. Thursday, April 7, at the DoubleTree Hotel, 1111 Jefferson Road.

The showcase's poster session is an opportunity for university researchers to present their work to industry as well as other researchers and organizations that promote economic development. The objective is to stimulate discussions that may lead to industry-university collaboration.

For example, thanks to connections established at a previous CEIS showcase, at least one European digital laser cinema company has expressed interest in the work of John Marciante, Associate Professor of Optics, who is developing a resonant optical de-excitation process which, when used in conjunction with terbium-doped glass fibers, could greatly increase the power and efficiency of visible lasers. (Read more here.)

Registration for this event will close by March 29.

CFAR announces new funding opportunity

The Centers for AIDS Research (CFAR) has announced a new funding opportunity for early stage investigators and for established investigators in non-HIV fields who have never received an NIH research award for HIV/AIDS studies. Applications will be accepted in these areas:

1. Tracking HIV Transmission Phylodynamics: Leveraging Collaborations with Public Health Departments and Others to Research Methods to Analyze Phylogenetic Data in Close to Real-Time (up to $200,000 DC)
2. HIV and Host Factor Targets for Structural Research (up to $200,000 DC)
3. Advancing PrEP Delivery (up to $200,000 DC)
4. Rapid HIV Treatment Initiation: Implementation Models, Uptake, and HIV Care Continuum Outcomes (up to $100,000 DC)
5. Drug-Drug Interactions in the Context of Antiretroviral Treatment and HIV Co-Infections and Comorbidities (up to $100,000 DC)

See the full CFAR supplement announcement for more details.

Investigators interested in applying should select one of the five areas and submit the following to by April 5:

1 page Specific Aims (briefly describe how the aims link to the selected area)
1 page description of expected outcomes, followup plan and "value added"
NIH Bio for PI

Selected applicants will be notified no later than April 12.

CFAR offers grant review services for HIV/AIDS applications

To support and develop the next-generation of HIV/AIDS researchers at the University, the Center for AIDS Research has implemented not only pilot funding, but a mentoring/grant review service. This provides new, early stage or established investigators new to the field of HIV/AIDS with advice and comments on grant proposals, in a friendly, informal environment.

Investigators can use this service for:

1. Proposal shaping: Investigators orally present their draft specific aims in a "chalk talk" format (without slides) to a customized ad hoc review panel of faculty members chosen from the CFAR Mentor Pool. The panel will discuss the draft aims and overall approach of the proposal with the investigator in an oral review session. The panel will also assist the investigator in identifying potential collaborators, as needed.

2. Proposal refinement: At least one month prior to an NIH deadline, a full proposal draft will be circulated to the same review panel. The panel will then meet in person to review the proposal, and will provide a written "summary statement" to the investigator, as well as in-person feedback if desired, within 10 working days.

More information can be found here. To take advantage of this service contact

Registration now open for NIH regional grant seminars

The National Institutes of Health spring and fall 2016 regional seminars on program funding and grants administration will be held:

1. Wednesday to Friday, May 11-13, 2016 in Baltimore, MD
2. Wednesday to Friday, Oct. 26-28, 2016 in Chicago, IL

The seminars are a great opportunity for researchers and research administrators to connect with NIH and HHS staff individually through one on one meetings, and through presentations on topics ranging from peer review and grant writing, finding the right funding opportunity, animals and human subjects in research, pre- and post-award management, special programs, and more. Learn more here.

University researchers in the news

A new study in the journal Nature Communications shows that cells normally associated with protecting the brain from infection and injury also play an important role in rewiring the connections between nerve cells. The discovery sheds new light on the mechanics of neuroplasticity, and could also help explain diseases like autism spectrum disorders, schizophrenia, and dementia, which may arise when this process breaks down and connections between brain cells are not formed or removed correctly. "We have long considered the reorganization of the brain's network of connections as solely the domain of neurons," said Ania Majewska, an Associate Professor of Neuroscience and senior author of the study. "These findings show that a precisely choreographed interaction between multiple cells types is necessary to carry out the formation and destruction of connections that allow proper signaling in the brain." The study is another example of a dramatic shift in scientists' understanding of the role that the immune system, specifically cells called microglia, plays in maintaining brain function. Read more . . .

Cloud computing software has brought many changes to the business landscape, and the implementation of such a service is common. New research from the Simon Business School sheds light on the growing competition between two widely used software models, Software-as-a-Service (SaaS), and Modified off-the-Shelf (MOTS) software. "The key factor that drives competitive business strategies in this highly aggressive market is the provider's pricing scheme," says Abraham Seidmann, Xerox Professor of Computers and Information Systems and Operations Management. SaaS is available online on-demand, which allows businesses to increase production with fewer people. The typical in-house MOTS system provides some API's (application program interfaces) with access to the source code of the underlying software so it can be customized and better integrated to the business. Read more . . .

Congratulations to . . .

Charles Thornton, the Saunders Family Distinguished Professor in Neuromuscular Research and Professor of Neurology, who has received a Javits Neuroscience Investigator Award from the National Institutes of Health to further his research on muscular dystrophy. The unique award provides "exceptional" researchers with seven years of uninterrupted funding. In a study appearing in the journal Nature in 2012, Thornton and his Medical Center colleagues, partnering with researchers at Ionis Pharmaceuticals, showed that drug treatment can largely reverse the muscle problems in mice with myotonic dystrophy. This approach is now being tested in patients. The Javits Award will help the team refine the treatment and learn more about how to maximize its beneficial effects and minimize its risks. Read more . . .

David Cameron, a visiting scientist in Eric Mamajek's research group in the Department of Physics and Astronomy, who discovered a new short-period comet — named Comet P/2015 PD229 (ISON-Cameron) — last August while analyzing images taken in May 2015 by Mamajek at the Cerro Tololo Inter-American Observatory in Chile. It is believed to be the first comet to be discovered by an astronomer associated with the University of Rochester or the Rochester area in over a century. Read more . ..

PhD dissertation defense

Letitia Jones, Microbiology and Immunology, "Modeling HIV-Induced, Blood-Brain Barrier Dysfunction in Mice." 9:30 a.m., March 24, 2016, K207 (2-6408). Advisor: Sanjay Maggirwar.

Mark your calendar

March 15: Network Capacity, presented by Karl Kieburtz, Co-Director, Clinical and Translational Science Institute; Karen Rabinowitz, Center for Human Experimental Therapeutics; and Carrie Dykes, Research Engagement Specialist, Clinical and Translational Science Institute. Noon to 1 p.m., Helen Wood Hall Auditorium (1w-304). Part of CTSI Seminar Series.

March 18: Social Supports and Health, presented by Ann Marie White, Associate Professor of Psychiatry. Noon to 1 p.m., Helen Wood Hall Auditorium (1w-304). Public Health Grand Rounds.

March 22: Hub Research Capacity, presented by Nancy Bennett, Director, Center for Community Health; Steven Barnett, Director, National Center for Deaf Health Research; and Giovanni Schifitto, Professor of Neurology. Noon to 1 p.m., Helen Wood Hall Auditorium (1w-304). CTSI Seminar Series.

March 29: Network Science/Regulatory Science, presented by Martin Zand, Co-Director, Clinical and Translational Science Institute; 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 31: "Seeing Stars: How Astronomy has enabled New Visions of the Living Eye," presented by Jesse Schallek, Assistant Professor, Ophthalmology, Neurobiology and Anatomy, and the Center for Visual Science. Phelps Colloquium, 4-5:30 p.m., Meiliora 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 15-16: Harded 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.

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.

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