From Vanderbilt: “Unraveling genetic mystery next step in Zika and dengue fight”

Vanderbilt U Bloc

Vanderbilt University

Apr. 23, 2018
Heidi Hall
(615) 322-NEWS
heidi.hall@vanderbilt.edu

A Vanderbilt team took the next leap forward in using a little-known bacteria to stop the spread of deadly mosquito-borne viruses such as Zika and dengue.

Wolbachia are bacteria that occur widely in insects and, once they do, inhibit certain pathogenic viruses the insects carry. The problem with using Wolbachia broadly to protect humans is that the bacteria do not normally occur in mosquitoes that transmit Zika and dengue. So success in modifying mosquitoes relies on the bacteria’s cunning ability to spread like wildfire into mosquito populations.

Wolbachia do so by hijacking the insect reproductive system in a process called cytoplasmic incompatibility, or CI. This makes the sperm of infected fathers lethal to eggs of uninfected mothers. However, if infected fathers mate with infected mothers, the eggs live, and the infected mothers carrying Wolbachia will also infect all her offspring with it. Then those offspring pass on Wolbachia to the next generation, and so on, until they eventually replace all of the resident mosquitoes. As Wolbachia spreads in the population, the risk of dengue and Zika virus transmission drops.

How that sperm and egg hijacking worked in infected fathers and mothers remained a mystery for decades, until Associate Professor of Biological Sciences Seth Bordenstein and his team helped solve it. They set out to dissect the number and types of genes that Wolbachia use to spread with the long-term goal of harnessing that genetic ability for protecting humans against diseases transmission.

“In this new study, we’ve dissected a simple set of Wolbachia genes that replicate how Wolbachia change sperm and egg” Bordenstein said. “There are two genes that cause the incompatibility, and one of those same genes rescues the incompatibility. Engineering mosquitoes or Wolbachia for expression of these two genes could enhance or cause the spread of Wolbachia through target mosquito populations.”

Their achievement is based on inserting genes into the genome of fruit flies. It is described in a paper appearing today in the Proceedings of the National Academy of Sciences.

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Wolbachia spreads itself by hijacking the insect reproductive system in a process called cytoplasmic incompatibility, or CI. (J. Dylan Shropshire/Vanderbilt University)

In a previous study last year Nature, the team identified the two genes in Wolbachia — named cytoplasmic incompatibility factors cifA and cifB — and learned that they modify the sperm to kill eggs. Now they solved the other half of the genetic mystery: cifA single-handedly can protect embryos from death.

“It’s a microbial encryption and de-encryptyion system that ensures Wolbachia spread through insect populations so they can adequately block the transmission of viruses and ultimately save lives” Bordenstein said.

Coauthors of the paper include Ph.D. student and National Science Foundation Graduate Research Fellow J. Dylan Shropshire and Vanderbilt undergraduates Emily Layton and Helen Zhou.

Vanderbilt University has filed patent applications on this new finding and seeks industry partners for further development through its Center for Technology Transfer and Commercialization.

This work was supported by National Institutes of Health (NIH) awards R01 AI132581 and R21 HD086833, National Science Foundation award IOS 1456778, a National Science Foundation Graduate Research Fellowship, and Vanderbilt University Medical Center Cell Imaging Shared Resources (supported by NIH grants CA68485, DK20593, DK58404, DK59637 and EY08126).

See the full article here .

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Commodore Cornelius Vanderbilt was in his 79th year when he decided to make the gift that founded Vanderbilt University in the spring of 1873.

The $1 million that he gave to endow and build the university was the commodore’s only major philanthropy. Methodist Bishop Holland N. McTyeire of Nashville, husband of Amelia Townsend who was a cousin of the commodore’s young second wife Frank Crawford, went to New York for medical treatment early in 1873 and spent time recovering in the Vanderbilt mansion. He won the commodore’s admiration and support for the project of building a university in the South that would “contribute to strengthening the ties which should exist between all sections of our common country.”

McTyeire chose the site for the campus, supervised the construction of buildings and personally planted many of the trees that today make Vanderbilt a national arboretum. At the outset, the university consisted of one Main Building (now Kirkland Hall), an astronomical observatory and houses for professors. Landon C. Garland was Vanderbilt’s first chancellor, serving from 1875 to 1893. He advised McTyeire in selecting the faculty, arranged the curriculum and set the policies of the university.

For the first 40 years of its existence, Vanderbilt was under the auspices of the Methodist Episcopal Church, South. The Vanderbilt Board of Trust severed its ties with the church in June 1914 as a result of a dispute with the bishops over who would appoint university trustees.

kirkland hallFrom the outset, Vanderbilt met two definitions of a university: It offered work in the liberal arts and sciences beyond the baccalaureate degree and it embraced several professional schools in addition to its college. James H. Kirkland, the longest serving chancellor in university history (1893-1937), followed Chancellor Garland. He guided Vanderbilt to rebuild after a fire in 1905 that consumed the main building, which was renamed in Kirkland’s honor, and all its contents. He also navigated the university through the separation from the Methodist Church. Notable advances in graduate studies were made under the third chancellor, Oliver Cromwell Carmichael (1937-46). He also created the Joint University Library, brought about by a coalition of Vanderbilt, Peabody College and Scarritt College.

Remarkable continuity has characterized the government of Vanderbilt. The original charter, issued in 1872, was amended in 1873 to make the legal name of the corporation “The Vanderbilt University.” The charter has not been altered since.

The university is self-governing under a Board of Trust that, since the beginning, has elected its own members and officers. The university’s general government is vested in the Board of Trust. The immediate government of the university is committed to the chancellor, who is elected by the Board of Trust.

The original Vanderbilt campus consisted of 75 acres. By 1960, the campus had spread to about 260 acres of land. When George Peabody College for Teachers merged with Vanderbilt in 1979, about 53 acres were added.

wyatt centerVanderbilt’s student enrollment tended to double itself each 25 years during the first century of the university’s history: 307 in the fall of 1875; 754 in 1900; 1,377 in 1925; 3,529 in 1950; 7,034 in 1975. In the fall of 1999 the enrollment was 10,127.

In the planning of Vanderbilt, the assumption seemed to be that it would be an all-male institution. Yet the board never enacted rules prohibiting women. At least one woman attended Vanderbilt classes every year from 1875 on. Most came to classes by courtesy of professors or as special or irregular (non-degree) students. From 1892 to 1901 women at Vanderbilt gained full legal equality except in one respect — access to dorms. In 1894 the faculty and board allowed women to compete for academic prizes. By 1897, four or five women entered with each freshman class. By 1913 the student body contained 78 women, or just more than 20 percent of the academic enrollment.

National recognition of the university’s status came in 1949 with election of Vanderbilt to membership in the select Association of American Universities. In the 1950s Vanderbilt began to outgrow its provincial roots and to measure its achievements by national standards under the leadership of Chancellor Harvie Branscomb. By its 90th anniversary in 1963, Vanderbilt for the first time ranked in the top 20 private universities in the United States.

Vanderbilt continued to excel in research, and the number of university buildings more than doubled under the leadership of Chancellors Alexander Heard (1963-1982) and Joe B. Wyatt (1982-2000), only the fifth and sixth chancellors in Vanderbilt’s long and distinguished history. Heard added three schools (Blair, the Owen Graduate School of Management and Peabody College) to the seven already existing and constructed three dozen buildings. During Wyatt’s tenure, Vanderbilt acquired or built one-third of the campus buildings and made great strides in diversity, volunteerism and technology.

The university grew and changed significantly under its seventh chancellor, Gordon Gee, who served from 2000 to 2007. Vanderbilt led the country in the rate of growth for academic research funding, which increased to more than $450 million and became one of the most selective undergraduate institutions in the country.

On March 1, 2008, Nicholas S. Zeppos was named Vanderbilt’s eighth chancellor after serving as interim chancellor beginning Aug. 1, 2007. Prior to that, he spent 2002-2008 as Vanderbilt’s provost, overseeing undergraduate, graduate and professional education programs as well as development, alumni relations and research efforts in liberal arts and sciences, engineering, music, education, business, law and divinity. He first came to Vanderbilt in 1987 as an assistant professor in the law school. In his first five years, Zeppos led the university through the most challenging economic times since the Great Depression, while continuing to attract the best students and faculty from across the country and around the world. Vanderbilt got through the economic crisis notably less scathed than many of its peers and began and remained committed to its much-praised enhanced financial aid policy for all undergraduates during the same timespan. The Martha Rivers Ingram Commons for first-year students opened in 2008 and College Halls, the next phase in the residential education system at Vanderbilt, is on track to open in the fall of 2014. During Zeppos’ first five years, Vanderbilt has drawn robust support from federal funding agencies, and the Medical Center entered into agreements with regional hospitals and health care systems in middle and east Tennessee that will bring Vanderbilt care to patients across the state.

studentsToday, Vanderbilt University is a private research university of about 6,500 undergraduates and 5,300 graduate and professional students. The university comprises 10 schools, a public policy center and The Freedom Forum First Amendment Center. Vanderbilt offers undergraduate programs in the liberal arts and sciences, engineering, music, education and human development as well as a full range of graduate and professional degrees. The university is consistently ranked as one of the nation’s top 20 universities by publications such as U.S. News & World Report, with several programs and disciplines ranking in the top 10.

Cutting-edge research and liberal arts, combined with strong ties to a distinguished medical center, creates an invigorating atmosphere where students tailor their education to meet their goals and researchers collaborate to solve complex questions affecting our health, culture and society.

Vanderbilt, an independent, privately supported university, and the separate, non-profit Vanderbilt University Medical Center share a respected name and enjoy close collaboration through education and research. Together, the number of people employed by these two organizations exceeds that of the largest private employer in the Middle Tennessee region.
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