Our researchers also seek to establish the cellular and systemic mechanisms by which animal and human hosts respond immunologically to pathogens and to vaccines.
The researchers’ goal is to combine these efforts in several different methods of vaccine delivery to develop heterologous prime boost vaccines to enhance productivity of agriculturally important farm animals and to improve human health throughout the world. The center is involved in two major lines of research: vaccine development to prevent a range of human and animal diseases, and biofuel development using photosynthetic bacteria to provide a renewable and carbon neutral source of energy. Both lines of research use our extensive expertise in genetic design and modification of bacteria to solve global problems facing humanity. Focal areas include:
Our overall research goal is to improve the quality of life for rural poor in Africa by increasing returns from family chicken flocks. Poultry production is an integral part of village life in Africa. Households rely on backyard flocks for food and income. Usually, indigenous chickens in family flocks perform poorly.
Our aim is to substantially increase backyard poultry production by introducing a high-performing, vaccinated hybrid chicken called Kuroiler. This is a low-maintenance, highly productive scavenger chicken that thrives in village environments. It’s estimated that each family with Kuroiler chickens will produce twice the amount of meat and four times the number of eggs compared to local indigenous chickens, thus generating over three times the income typical from indigenous flocks.
The principal beneficiary would be impoverished families, particularly women, in Ugandan villages. Participating families will see a rapid and remarkable increase in the availability of eggs and meat. Additional family income will be generated from the sale of surplus poultry products.
Improved family nutrition should reduce the negative impact of malnutrition on child development, enhance immune competence, and reduce the incidence of infectious and non-infectious diseases. Because the proposed work will establish a financially self-sustaining chicken distribution system, the villagers will benefit from new entrepreneurial opportunities for poultry extension workers, dealers, mother unit owners and vendors.
Nerve toxin antidotes
A class of compounds known as organophosphates (OPs) are among the deadliest nerve agents in existence. They take effect by disabling the nervous system’s ability to clear away neurotransmitters, causing continuous nerve activation, prolonged muscle contractions, cardiovascular and respiratory collapse. Organophosphates are prevalent in many pesticides and are a leading cause of accidental poisoning worldwide. More frighteningly, organophosphate toxins have been developed into weaponized nerve agents that can be used against human populations, with catastrophic consequences.
At the Biodesign Institute, researchers are taking bold steps to combat the growing threat of accidental or deliberate organophosphate poisoning from pesticides or lethal nerve agents like sarin and VX. In the laboratory of Dr. Tsafrir Mor, this work involves the innovative use of plants as living factories to produce potent nerve agent antidotes.
Normally, human proteins like acetylcholinesterase (AChE) act as bioscavengers, patrolling the body and cleaning up toxic organophosphates before they can cause harm. OP nerve agents however, can act to disarm these bioscavengers, leaving the victim without defense as unregulated neurotransmitter molecules accumulate in the victim’s synapses. The result, known as a “cholinergic crisis” leads to prolonged muscle contractions and fatal paralysis of respiratory organs. Such deadly organophosphate weapons have been used during Iraq’s war with Iran and more recently, in terrorist attacks in the Tokyo subway in the mid-1990s.
The project team is attempting to use plants to synthesize bioscavenging proteins in sufficient quantity that they may be used to prevent or more effectively treat OP poisoning. To date, the most successful bioscavengers under study are human cholinesterases (ChEs), which mop up excess particles of the neurotransmitter acytylcholine, preventing it from building up in the synaptic spaces between nerves. Once synthesized in plants, these bioscavengers may be introduced into the human body where they not only bind with and neutralize nerve agents but actually break down and destroy the organophosphate poison.
West Nile Therapeutics
ASU has assembled some of world’s greatest research expertise in plant-based vaccines and therapeutics, and now we want to apply that knowledge to address the leading mosquito-borne health threat in the U.S.,” said Qiang “Shawn” Chen. Chen is a researcher at Arizona State University’s Biodesign Institute and a professor in the Polytechnic Campus’ College of Technology and Innovation. He is the first to demonstrate a plant-derived treatment to successfully combat West Nile virus after exposure and infection.
West Nile virus has made alarming inroads in North America, causing disease outbreaks throughout the U.S., as well as in areas of Canada, Mexico, the Caribbean and South America. Elderly individuals and those with depressed immunity are particularly vulnerable to West Nile, a mosquito-borne illness which can cause a potentially lethal inflammation of the brain. “We have made a new therapeutic made from tobacco plants has been shown to arrest West Nile virus infection,” said Chen. “First, we wanted to show proof-of-concept, demonstrating that plant-made antibodies can work as effective post-exposure therapeutics. Secondly, we’ve sought to develop a therapeutic which can be made inexpensively so that the health care systems in developing countries can afford it.”
While the group’s focus has been on West Nile Virus, Chen believes the plant-based antibody approach could provide highly effective, cost efficient therapeutics for other diseases, including related flavivirus infections such as dengue fever and Japanese encephalitis, if the successes in mice can be replicated in humans. Chen is now working on bifunctional antibodies, capable of binding with virus particles as well as attaching to receptors in the brain, allowing the antibody to migrate past the blood brain threshold. If successful, the technique may allow treatment of other, currently intractable infectious and neurological diseases.
Tuberculosis—one of the most harmful human infectious diseases—kills two million people worldwide every year. According to the World Health Organization, one third of the world’s population is infected with Mycobacterium tuberculosis, causative agent of the illness, with 8 million cases diagnosed annually. New infections are occurring at a rate of about one per second, with a growing percentage of recent cases showing multi-drug resistance.
We are working on several active fronts to combat tuberculosis, a scourge that has persisted throughout recorded history. While the challenges are daunting, significant progress is being made. Understanding the subtle mechanisms by which M. tuberculosis bacteria causes TB is one of the central goals of the Institute’s Center for Infectious Diseases and Vaccinology.
M. tuberculosis is highly contagious, but to contract the disease, two stages are required: first, an individual must be infected with the bacterium; second, the infection must progress to the disease stage. Transmission occurs through the dispersal of nasal droplets from an infected carrier. The ingestion of a single M. tuberculosis bacterium is enough to cause infection, though only about one in ten latent infections will develop into active tuberculosis. About half of these patients will die if the infection is left untreated.
While the body’s natural defenses can usually stave off the activation of tuberculosis, the bacteria, once ingested, can remain viable, persisting in a dormant state. Should the body’s immune system weaken for any reason, the mycobacteria can spread and then attack. Those most vulnerable to tuberculosis include people under immunosuppressant therapy and anyone suffering from immune diseases, particularly HIV. For individuals co-infected with TB and HIV, tuberculosis is now the leading cause of death, and is responsible for 13 percent of all AIDS fatalities worldwide.
Research has focused on understanding the specific genes that permit tuberculosis bacteria to survive and grow within human macrophages—specialized cells whose role it is to seek out and destroy infectious bacterial invaders.
Tuberculosis is notoriously difficult to treat, requiring a lengthy regimen of drugs, often unavailable in areas where they are most needed—tubercular hot spots throughout the developing world. One of the most exciting branches of research at Biodesign is aimed at the development of a safe, low cost vaccine. A novel strategy under development at Biodesign involves the use of an attenuated Salmonella vaccine carrier, capable of generating a powerful, sustained immune response to infectious bacilli.