In a laboratory in Chicago, a doctor called Hope is hunting the human immunodeficiency virus (HIV) that causes AIDS with a microscope so powerful that scientists call it the OMG microscope.
Thomas Hope is a professor of cell and molecular biology at the Hope HIV Laboratory at Northwestern University. He’s is among a group of researchers using advanced tools developed by GE Healthcare Life Sciences to study the disease, control the virus that causes it and push for the obvious next step – a cure.
Top image: “We’re really starting to identify which cells get infected first, and where they are located,” says Northwestern’s Tom Hope. Above: An HIV-infected T-cell. Image credit: NIAID
Dr. Hope is using a high-definition microscope from GE to learn how HIV infects a cell and then spreads to other cells. His goal is to prevent the initial infection. This microscope — GE Healthcare Deltavision OMX — uses advanced algorithms and high-definition cameras that allow researchers to observe living organisms and viruses in 3D even beyond Ernst Abbe’s diffraction barrier, once the final frontier for microscopic resolution. (The barrier prevented researchers from seeing two objects closer to each other than half the wavelength of light they used to image the sample.) As a result, scientists can use it to study objects as small as 120 nanometers, about 1,000th the width of a piece of human hair.)
Unlike a typical microscope, the machine does not have an ocular lens or a traditional stand. Instead, scientists place samples on a platform inside the machine and photograph them using high-definition cameras. Rather than shining light at the sample, they attach colored fluorescent molecules, called probes, to parts of viruses and cells. The light emitted by the probes then illuminates things that were previously obscured.
The technology allows Dr. Hope and his team to highlight different segments of the HIV virus and the cells it tries to infect. “We’re really starting to identify which cells get infected first, and where they are located,” Dr. Hope says. “That sets the stage for us to really begin to pick that apart. The Deltavision became … the instrument of choice for a whole lot of HIV work.”
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“We have nice evidence of disrupting envelope trafficking and stopping the spread of the virus,” says Emory’s Paul Spearman.
One of the pathways his team has been dissecting is that which places the HIV envelope protein (Env) onto developing particles. By manipulating cellular recycling pathways, Spearman and his team have been able to arrest Env trafficking in a discrete compartment called the endosomal recycling compartment. By trapping Env in this compartment, the viruses that assemble are rendered noninfectious. “We have nice evidence of disrupting envelope trafficking and stopping the spread of the virus,” Spearman says. “We have been using Deltavision for about seven years, and now we are learning new details of the assembly pathway using the OMX.”
He says once the Env trafficking pathway is fully understood, he can work on developing an inhibitor.
“We take blood cells from HIV-infected people, particularly those who are able to control their infections,” says Vanderbilt’s James Crowe . “There may be clues in their immune response as to how to resist HIV. We’re studying antibodies made by these individuals.”
The Deltavision system isn’t the only GE technology researchers are using to find a cure for HIV. Dr. James Crowe, director of the Vanderbilt Vaccine Center, uses GE Healthcare Life Sciences technology to isolate, purify and characterize batches of individual monoclonal antibodies in order to study people who are unusually resistant to HIV. He believes these patients — called “controllers” or “nonprogressors” — could hold the key to developing a vaccine.
Controllers live as long as 20 years before HIV becomes AIDS — Acquired Immune Deficiency Syndrome — twice as long as most patients. “We take blood cells from HIV-infected people, particularly those who are able to control their infections,” Crowe says. “There may be clues in their immune response as to how to resist HIV. We’re studying antibodies made by these individuals.”
He is getting closer to finding out what makes them special, and how to leverage their unique immune response to reach the holy grail of HIV research: a vaccine.
Working in a high-safety laboratory, he mixes the purified monoclonal antibodies with live HIV cells and incubates them. “Then we see if the virus can still replicate in cells, and if the antibodies inhibit the replication of the virus … a process called neutralization,” he says. “That’s the function we’re looking for. That’s the moment of truth: when we know if these antibodies are really potentially useful.”
Cindy Collins, general manager of in vitro diagnostics, research and applied markets at GE Healthcare Life Sciences, says, “A decade ago, it seemed unimaginable that we might one day see a cure for HIV. While much work remains to be done, the groundbreaking work of these researchers gives us hope that this may not be such a far-off reality. Our focus is to continue to develop the technology that will enable and advance their research.”
The GE Healthcare Deltavision OMX™ and AKTA™ Protein Purification Systems are for research use only. They are not for diagnostic or therapeutic purposes.