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Functional genomics lab to predict potential AIDS vaccines efficacy and find protection markers

Posted on July 11, 2013

A national resource for predicting the efficacy of potential AIDS vaccines is being established at the University of Washington. The new functional genomics laboratory aims to measure vaccine responses at a molecular level, and discover markers that may be prognostic in assessing if a vaccination will protect against HIV.

The National Institute of Allergy and Infectious Diseases of the National Institutes of Health has announced the award of a five-year, nearly $15 million contract, including the exercise of all options, to the UW for the Nonhuman Primate Core Functional Genomics Laboratory for AIDS Vaccine Research and Development.

Virus expert Dr. Michael Katze (lower panel ) stands in front of the liquid handling robot that will process an estimated 4,000 samples per year for analysis by the functional genomics core laboratory. Processed samples are used to generate the expression levels of more than 20,000 genes, visualized in an array (panel upper left). With such array measurements on many samples, the Core will apply advanced statistical and mathematical techniques to understand the changes that occur during the course of vaccination and infection (panels upper center and right). Image credit: Robert Palermo and Sean Proll

Virus expert Dr. Michael Katze (lower panel ) stands in front of the liquid handling robot that will process an estimated 4,000 samples per year for analysis by the functional genomics core laboratory. Processed samples are used to generate the expression levels of more than 20,000 genes, visualized in an array (panel upper left). With such array measurements on many samples, the Core will apply advanced statistical and mathematical techniques to understand the changes that occur during the course of vaccination and infection (panels upper center and right). Image credit: Robert Palermo and Sean Proll

The lab will apply leading-edge biotechnology, biocomputing tools and systems biology approaches to conduct this service. It is anticipated to make inventive improvements in vaccine services and assays.

The principal investigator is Dr. Michael Katze, a UW professor of microbiology who pioneered systems biology to understanding immune responses to infections. He and his colleagues examine the network of responses and interactions between pathogens and their hosts, as well as the factors that influence the dynamics of this struggle.

“The AIDS vaccine field is in need of new approaches. The methods we use allow us to understand the gene expression changes that correlate with vaccine efficacy and will help to design better vaccines,” Katze said.

Their laboratory will receive specimens obtained from ongoing and new high-priority preclinical non-human primate studies conducted in the National Institute of Allergy and Infectious Diseases Division of AIDS Simian Vaccine Evaluation Units and other Division of AIDS -supported preclinical non-human primate studies across the country.  It will become the fourth Simian Vaccine Evaluation Units Core Lab in this effort to end the AIDS epidemic. The existing Simian Vaccine Evaluation Units Core Labs, located at other institutions, cover other aspects of AIDS vaccine preclinical research in non-human primates:  the Humoral Immunology Core Lab, the Cellular Immunology Core Lab, and the Viral RNA Core Lab.

The new UW Non-Human Primate Core Functional Genomics Lab will test specimens to generate specific genomic expression profiles using approaches developed by UW microbiologist Dr. Robert Palermo and other UW research scientists. These profiles are a time-record of gene activity, and rapidly examine many genes at once. The profile reveals those segments of the organism’s genome that are being dynamically utilized. The transcription of information coded in the DNA is the first step in producing a protein to carry out a biological function.

After measuring how experimental conditions alter which genes are turned on or off, a systems-level view is derived. This analysis uses sophisticated mathematical techniques, interaction networks, and computer modeling.  In this approach, other types of data from the vaccine studies are integrated with the genomic expression profiles to find potential predictive signatures. The list of RNA molecules discovered during such characterizations offer clues to the events taking place inside and around living cells.

In evaluating potential AIDS vaccines, data analyzed in this way may point to gene signatures that suggest how much protection a vaccine is expected to provide against HIV. Checking for and measuring gene signatures after vaccination and virus exposure could in part explain a vaccine’s effectiveness in preventing or controlling an infection by illuminating the details of the immune mechanisms evoked by the vaccine.

Palermo commented:  “The vision of the Division of AIDS at the National Institute of Allergy and Infectious Diseases in establishing this Core is very exciting.  The work will inform not only the efforts of individual investigators, but will result in a compendium of such data across many studies and conditions. This will enable sophisticated computational approaches that are dependent on having very large amounts of data, and ideally will lead to insights not accessible with the results of a single study.”

The activities of the UW Non-human Primate Core Functional Genomics Lab will contribute to the many National Institute of Allergy and Infectious Diseases-funded efforts that target discovering effective preventive vaccines against AIDS.  National Institute of Allergy and Infectious Diseases supports testing a variety of candidate AIDS vaccines, and is exploring ways to optimize their ability to elicit immune responses that will prevent infection or control virus replication.

Source: University of Washington

   
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