The Hayhurst laboratory works on selected Tier 1 biothreat agents and develops novel antibody engineering approaches to find new routes to detect and inhibit pathogens. Using live agent selections, his team develops antibodies that can recognize native biothreat antigens in a highly specific and sensitive manner. These antibodies are rugged enough for transition to biosensors and field portable diagnostics to withstand very harsh conditions, (e.g. in resource-poor areas of the world with limited electricity and refrigeration).
His lab has developed llama single domain antibodies (sdAb) specific for Ebola virus and Marburg virus, two viruses that cause hemorrhagic fever and a very high mortality rate.
Dr. Hayhurst and his team also developed an assay to recognize all serotypes of the botulinum neurotoxin, one of the most poisonous substances currently known.
The redesign of the surfaces of microbes allows us to “educate” them to perform simple tasks of interest to therapeutic and nanotechnology communities and is a recent focus of the Hayhurst lab.
- Ebola virus
- Marburg virus
- Botulinum neurotoxins
- Novel cancer therapeutics
Dr. Hayhurst contributes more than 20 years of experience in microbiology and antibody engineering.
Pictured from left to right: Casey Sparks, visiting Graduate Student; Tamarand Darling, Ph.D. student; Dr. Andrew Hayhurst; Laura Sherwood, Senior Research Associate
In The Lab
Many biothreat agents lack high quality antibodies that are essential for the development of immunoassays and help to facilitate molecular studies. To circumvent this problem, we established an antibody pipeline to rapidly select and screen sdAb specific for BSL-4 agents. Our group was the first to apply single-pot selection to a live BSL-4 agent and we developed a highly sensitive assay for Marburg virus within only three weeks. Using our single-pot methodology, we also developed assays for five Ebola virus species and serendipitously revealed a common antigenic attractant within the nucleoprotein for all single domain antibodies (sdAb).
One focus has been on accelerating antibody screening within a viral sandwich assay to formulate stop-gap diagnostic assays. Our novel process rapidly identifies pairs of affinity reagents, including sdAb, without the need for protein purification. The approach relies upon the temporal occlusion of in-vivo biotin by neutravidin to enable “captors” and “tracers” to be sourced from the same extract. The ease, speed, and cost-effectiveness of the technology ensure that affinity reagent pairing is very straightforward, requires no sophisticated equipment, and accelerates the discovery of high performance antibodies.
Our research emphasis is moving on from reagent development and into more basic science as we study the molecular basis for recognition of the viral antigens by our sdAb using X-ray crystallography, in collaboration with Drs. Alex Taylor and John Hart at the UTHSCSA crystallography core laboratory. We are applying this information to guide antibody engineering to close the gap between immunoassay and nucleic acid based detection; our new strategies should be applicable to several RNA viruses to help safeguard human health.
Botulism, a muscle-paralyzing and potentially fatal disease, is caused by neurotoxins produced by the bacterium Clostridium botulinum. Using immune llama antibodies, our lab has been targeting the botulinum neurotoxins, estimated to be 100 billion times more toxic than cyanide. We have successfully engineered a heptaplex assay to recognize the seven known serotypes of the neurotoxin based upon sdAb, all of which have proved to be suitable for making multiplex biosensor platforms more rugged.
Our lab is also exploring the potential for reprogramming the surfaces of bacteria and viruses to enable them to more effectively target tumors. We are currently examining the limits of microbial cell surface display in terms of payload and degree of access to target antigens on mammalian target cells in contrast to typical solution phase antigens and substrates.
Main Technologies And Methods Used
- Recombinant antibody generation
- Phage display of peptides and proteins
- Rapid antibody pairing
- Protein engineering
- Directed evolution
- Protein production and purification
- Immunoassay development
- Novel therapeutic development