USU developing device to detect mad cow disease

Doan Nguyen

Utah State University bioengineers are proposing to develop a device that will be able to detect protein conformational diseases, such as mad cow disease, in beef.

The two-year project was granted $200,000 by the U.S. Department of Agriculture and will start this May. The University of Utah’s bioengineering department is collaborating with USU and will be subcontracted a part of the fund.

“We are trying to come up with a biosensor that can report the conformation, or shape, of a protein from a very simple approach,” bioengineering professor, David Britt said.

When proteins adopt an abnormal shape, such as in mad cow disease, the result is a pathogenic conformational disease.

The biosensors will recognize proteins based on shape and detect whether “dangerous conformations” are present. Britt said information from prior research on protein conformation supports the proposal.

The “dangerous conformations” also known as, “rogue conformations,” have a tendency to self-assemble to form plaques, which is the basis of prion diseases such as bovine spongiform encephalopathy (BSE), or mad cow.

The plaques lead to brain tissue degeneration and are thought to cause neurological disorders and symptoms in cattle. Similar diseases which affect other species are scrapie, in sheep, and chronic wasting disease, in elk. Creutzfeldt-Jakob and Alzheimer’s are diseases which occur in humans.

The biosensors will boost consumer security in beef products. The fundamental research may also open doors to produce a wide array of biosensors for other uses. Future sensors may be used by the military to detect biological warfare agents, while others may determine which allergens are floating in the air.

Bioengineers are in the early stages of developing the device and will not yet work with prion diseases.

“We first want to develop a proof of concept,” Britt said. Model proteins will be used instead of prion proteins. “We don’t want to work with anything hazardous at this stage.”

“I think in two years we will have a prototype that can be demonstrated for a nonpathogenic protein,” Britt said.

Britt said design of the sensor is based on the principle called “molecular imprinting.”

Molecular imprinting comes from the idea of the child’s game where block shapes are fit into complementary shaped cavities, he said.

On the molecular scale, researchers will create cavities (molecular imprints) complementary to a protein in terms of its size, shape and chemistry.

“The biosensor will only recognize a specific protein conformation,” Britt said. “For example, molecular imprints will be formed against the dangerous protein conformation in the laboratory, and then used to test for the presence of these proteins in cattle.”

“Molecular imprinting is like making a molecular mold that is specific to target molecules or proteins,”said Revathi Pepalla, a doctorate student studying biological and irrigation engineering.

Pepalla is working on the biosensors project as a part of her dissertation. Pepalla has had her research on molecular imprinting showcased at an Institute of Biological Engineering conference in Athens, GA.

“It is pretty exciting for me to work on this project,” Pepalla said, who works in Britt’s laboratory. “My experiments are going in the direction we envisioned. It just may be a matter of time.”

Britt’s researchers are hopeful that the molecular imprints may exhibit catalytic activity to help proteins return to normal shapes, he said.

“We’re trying to make molecular scale cavities that will detect the presence of pathogenic conformational proteins as well as allow them to go back into the correct conformation,” Britt said.

“I definitely believe that this research will be successful,” Pepalla said, “We started it with enough scientific backing.”

The project is in the process of bringing together an international team and will hire specialist, Nicholas Turner, from Cranfield University in the United Kingdom to work as a post doctoral associate.

“I am excited to have somebody who has extensive expertise in the molecular imprinting field to work on the project,” Britt said.

Clell Bagley, extension veterinarian and program leader of the agriculture and natural resources department, said he thinks testing cattle early on for prion disease would be the answer to consumer security in beef.

“The goal would be to develop a test that could detect the presence of prions earlier or in a live animal,” he said.

Bagley said today’s tests are conducted using brain tissue of cattle, where BSE most likely shows up, if in fact it is in the animal’s system. Cattle tested are those which show symptoms of “central nervous system disturbance” such as staggering.

Almost 200,000 cattle have been tested for BSE during the past 9 months, Bagley said. Several thousand were also tested each year prior to that for several years. All USDA tests have been negative. However, current procedures only test on slaughtered cattle.

“Brain tissue can only be collected after the animal is dead — it cannot be a biopsy while they are alive,” he said. “That is somewhat of a limitation, but the best available way so far.”

The results are statistical and don’t represent the entire population of live cattle lined up for consumption.

“There is no scientific justification for testing every animal,” Bagley said.

Pepalla said she thinks the technology could eventually evolve into real-time devices that recognize and separate target molecules of choice. Targets molecules such as ferritin, the protein Pepalla is currently working with, and prions.

-doantn@cc.usu.edu