Hospital to Lead National Research Team; Gains Powerful Device

The past few months have been notable ones for St. Jude Children's Research Hospital.

First it was announced in September that the hospital had acquired the first Ascend 1.1 GHz Nuclear Magnetic Resonance Spectrometer (NMR). It is the largest and most powerful device of its kind, according to hospital officials.

Then in late October it was learned that St. Jude will participate in a partnership to create more effective flu vaccines. The effort was brought by the approximately $51 million in total first-year funding by the National Institute of Allergy and Infectious Diseases (NIAID).

NIAD is part of the National Institutes of Health which initiated the Collaborative Influenza Vaccine Innovation Centers (CIVICs) program, a new network of research centers that will work together in a coordinated, multidisciplinary effort.

According to St. Jude, influenza vaccines remain the best way to protect against flu infections and serious, even deadly complications. But there is room to improve. In a good year, flu shots prevent infections in 70 to 90 percent of healthy children and adults under age 65.

The vaccine is less effective for those at greatest risk. These include children with cancer, people over 65, and those who are pregnant or obese. Also, at risk are those who have chronic illnesses, including diabetes and asthma. Scientists at St. Jude and the University of Georgia have been selected to help change that.

Goal: Improve Vaccines

"The goal is to develop vaccines that are more broadly protective against multiple flu strains. Our priority is vaccines to safeguard populations we know will develop more severe disease if infected," said Stacey Schultz-Cherry, PhD, of the St. Jude Department of Infectious Diseases. She also co-directs the Center of Excellence for Influenza Research and Surveillance at St. Jude.

Schultz-Cherry and Ted Ross, PhD, of the University of Georgia, will lead the new Center for Influenza Vaccine Research for High Risk Populations. A seven-year NIAD contract of up to $130 million will fund the work. The project will encompass 14 universities and research institutes.

In discussing the effort, NIAID Director Anthony S. Fauci, MD, said, "To more effectively fight influenza on a global scale, we need better influenza vaccines that are more broadly protective. With the CIVICs program we hope to encourage an exchange of ideas, technology and scientific results across multiple institutions to facilitate a more efficient and coordinated approach to novel influenza vaccine development."

The CIVICs centers will conduct multidisciplinary research that supports the development of vaccine candidates through testing in preclinical studies, clinical trials and human challenge studies. The CIVICs network also will explore approaches to improve seasonal influenza vaccines, such as by testing alternative vaccine platforms or incorporating new adjuvants (substances added to vaccines to boost immunity). These advances could substantially reduce influenza hospitalizations and deaths in the future.

The CIVICs program will include three Vaccine Centers, one Vaccine Manufacturing and Toxicology Core, two Clinical Cores, and one Statistical, Data Management, and Coordination Center (SDMCC).

Magnet Will Aid Research

St. Jude's acquisition of the first Ascend 1.1 GHz Nuclear Magnetic Resonance Spectrometer will allow its researchers to study proteins, DNA, RNA and other biomolecules to improve their understanding of the development of catastrophic diseases.

The device was made by Bruker Corporation, an American manufacturer of scientific instruments for molecular and materials research, as well as for industrial and applied analysis. It is headquartered in Billerica, Massachusetts.

The NMR will be used extensively by St. Jude's Structural Biology Department using the most advanced technologies to tackle important biological systems with the goal to understand health and disease at the molecular and atomic level. It is the centerpiece of the department's expansion, which is being led by Charalampos "Babis" Kalodimos, PhD, the department chair.

"This 1.1 GHz system provides unprecedented capabilities and opportunities for us to answer challenging biological questions," Kalodimos said. "It will be our most important tool to perform research in the area of dynamic molecular machines that are otherwise not amenable to other technologies."

With NMR technology, biological samples are placed inside the device's magnet, where they are bombarded with radio waves. This results in the emission of signals that are read by the spectrometer and translated into images, which provide a visual of how protein structures change and interact with other cellular molecules. Cells release signaling molecules that bind to receptors inside other cells that create changes. Abnormal messages can result in the creation of abnormal proteins that don't respond to normal cell signals and can grow unchecked. That growth is what causes cancer.

In addition to the NMR, Kalodimos has overseen other technological upgrades and enhancements to the department, which utilizes four frontline techniques to examine biomolecular structures: cryogenic electron microscopy and tomography, NMR spectroscopy, X-ray crystallography and single molecule imaging. Structural biologists combine the results from the use of each technique to understand the structures of complex biomolecular systems.

James R. Downing, MD, St. Jude president and CEO, said the addition of the NMR will significantly increase the technological infrastructure within the Structural Biology Department.

"With the expansion of the Structural Biology Department, we are creating the world's most comprehensive research center for defining the structure of the molecular machines that carry out basic functions within cells," Dr. Downing said. "This information will enhance our ability to understand what drives pediatric cancer and other catastrophic diseases of childhood, and, ultimately, advance cures for these diseases."