In a rapid process called yeast display, scientists screen a library of yeast cells to find candidates that specifically stick to particular antigens.Photo:
Zappys Technology Solutions.
Researchers and clinicians rely on proteins produced by animals’ immune systems, called antibodies, for applications ranging from cancer detection to diagnosing Clostridium difficile infections. But antibodies are expensive; generating a new one is a laborious, months-long endeavor, a delay that hinders the development of new diagnostic tests. Now, a new probe technology developed by researchers at the University of Washington and University of Queensland, Australia, which has been filed for patent, offers an alternative to antibodies that can be developed faster and at a fraction of the expense. The researchers have partnered with an Australian team to commercialize the innovation.
“For someone thinking broadly about new pathogens emerging in new places, you can’t get antibodies off the shelf rapidly enough,” said Professor Gerard Cangelosi, who is a professor in our department. He developed the new technology in collaboration with Matt Trau at the University of Queensland, Australia.
The properties that let researchers detect diseases in blood or stool samples using antibodies arise from their role as key components of the body’s natural defense mechanisms.
In the fight against infectious agents, the immune system deploys an arsenal of antibodies to act as specialized seek-and-destroy proteins. Antibodies circulate within the body and bind tightly to the surfaces of entities that don’t belong inside the host. Each antibody recognizes a specific structure, called an antigen, based on its three-dimensional properties; an antibody interlocks with its target antigen to identify and neutralize potential invaders.
The specificity of antibodies for their targets makes them useful tools in labs and clinics. To create antibodies, an isolated antigen is injected into an animal, such as a rabbit or a mouse. The injected animal’s immune system produces antibodies against that antigen, which researchers then must isolate.
The new probes improve upon antibodies because they can be inexpensively made in two to three weeks, without using animals. The production of the new probes is a rapid process based on a classic biological technique, called yeast display. In this approach, scientists screen a library of millions and millions of yeast cells, each genetically engineered to produce a unique antibody-like molecule, to find candidates that specifically stick to particular antigens. After identifying a promising probe, scientists generate large amounts of the isolated molecule for downstream applications.
Unfortunately, Cangelosi explains, when the probe is outside of the yeast cell, it never works. So, Cangelosi’s team kept the isolated probes attached to a portion of the yeast cell wall, maintaining the molecule in its optimal configuration for antigen binding.
The success of these detectors at pinpointing specific antigens was established in a publication in Biosensors and Bioelectronics, and a report in Analytical Chemistry, further demonstrated their versatility. The researchers have produced eight different probes able to distinguish antigens of the dysentery-causing amoeba, Enteromeba hemolytica.
Cangelosi hopes that the new probes will be used in molecular biology and diagnosis.
“Our vision,” he says, “is that anything you can do with an antibody you can do with these probes.”