Biology-Based Field of Study Represents New Frontier for Infectious Diseases Discovery

Infectious diseases researchers Daniel Hoft, MD, PhD, and Mei Xia, PhD, review RNA quality results while Azra Blazevic, DVM, examines purified T cells on samples to be sent for transcriptomics research. Courtesy of Ellen Hutti/Saint Louis University

Saint Louis University’s Vaccine and Treatment Evaluation Unit has received a five-year, $5.8 million contract from the National Institutes of Health to support an “omics” research initiative to study the safety and effectiveness of vaccines and other ways to fight infectious diseases.

“We’re building off genomics as we enter the omics revolution in our search for new safe and effective vaccines. In particular, we’re looking at how a host of systems trigger our bodies’ immune response to protect us from infectious diseases,” says Daniel Hoft, MD, PhD, SLU VTEU principal investigator and director of the division of infectious diseases and immunology at Saint Louis University.

“Previously we could only measure a few endpoint responses, such as the presence of an antibody or T cell responses to a specific antigen. But through omics studies, we will be able to use sophisticated technologies to determine all responses in the body necessary to marshal the immune system to best recognize and defend against bacteria, viruses and other harmful substances. This biological systems approach represents a new frontier of infectious diseases research.”

Through technological advances in omics, such as deep sequencing techniques and mass spectrometry, SLU researchers will explore four different areas that provide important information about the body’s immune response:

• Transcriptomics: Hoft, who also is principal investigator of the omics program, will lead the initiative that studies how RNA molecules, which can react to external conditions and translate our DNA in the body’s defense. Transcriptomics can tell when and where on the winding DNA molecule genes are turned on and off in cells.

• Proteomics: Yie-Hwa Chang, PhD, associate professor in SLU’s department of biochemistry and molecular biology, and David Wood, Ph.D., assistant research professor in SLU’s department of biochemistry and molecular biology, will examine the structure and function of proteins, such as antibodies, that are part of the immune system. Proteomics, which is the step after genomics and transcriptomics to study biological systems, is complicated because cells can make different proteins under varying circumstances.

• Lipidomics: David Ford, PhD, professor of biochemistry and molecular biology at SLU, will study the networks and pathways of lipids, which is a subset of metabolites, that includes fats such as triglycerides; sterols such as cholesterol; and fat-soluble vitamins. These compounds perform an assortment of biological processes such as participating in cellular signaling, serving as part of the structure of cell membranes and storing energy.

• Metabolomics: James Edwards, PhD, assistant professor of chemistry at SLU, will study metabolites, which are small molecules produced during life-sustaining chemical processes such as digestion. Metabolomics is a highly complicated and dynamic field, in which the end chemical reaction of one molecule can influence the beginning chemical reaction of another molecule.

“We need to look at how everything fits together to better understand the big picture of what is happening, specifically in the immune system,” Hoft says. “We’re trying to translate information beyond the DNA to see what else is required to generate a specific response.”

SLU’s Vaccine and Treatment Evaluation Unit is one of two sites in the country, designated by the National Institute of Allergy and Infectious Diseases, to conduct omics assessments on multiple potential vaccines and other interventions to protect against infectious diseases.

SLU is eligible to conduct the research because it was selected by the NIH in 2013 as one of nine institutions in the country to study vaccines of the future that will protect people from infectious diseases and emerging threats.

Through the contract (HHSN272201300021I), SLU will present original ideas for omics study as well as conduct omics analysis for other centers tapped by the NIH to study vaccines and other ways to protect people from infectious diseases. SLU’s first omics study will be of an investigational vaccine for tularemia, a rare and potentially fatal infectious disease that is passed from infected wild rodents to humans via bug bites or direct contact with a sick animal.

Source: Saint Louis University Medical Center