Associate Professor of Biology
Ph.D. Plant Pathology, Cornell University
M.S. Biological Sciences, Cal Poly Pomona
B.S. Biological Sciences, University of California, Irvine
Research Focus: Modulatory peptide discovery and biotechnology
We discover and develop novel peptides for low-cost, large-scale applications. We are especially interested in peptides and delivery systems that can solve Third-World problems.
1) Mosquitocidal nectar plants
Male mosquitoes feed exclusively on nectar while female mosquitoes need nectar to fuel their blood quest flights. Leveraging this biology, the Kearney Lab is developing a system to deliver mosquito-specific peptide toxins produced in nectar for imbibition by mosquitoes. In this way, the mosquitoes travel to the nectar to receive a dose of toxin that kills only mosquitoes. In contrast, pesticides kill a wide array of insects and must be sprayed in sufficient volume to reach all mosquitoes, since pesticides kill by direct contact. We have identified Impatiens walleriana as a plant which is highly attractive to mosquitoes and is easily transformed genetically (Chen and Kearney, 2015). Impatiens are the top selling flowering shade plant world-wide. We are developing this plant as a model system to study the delivery of anti-mosquito proteins through nectar to the mosquito. We have developed a mosquito-specific peptide and have an efficient impatiens transformation system in operation.
2) Biocomputing approaches to discover antimicrobial peptides and other modulatory peptides
Antimicrobial peptides are small proteins that protect against bacterial pathogens in humans, plants, insects and fungi. Antibiotics are chemicals that serve the same function, but pathogens resistant to antibiotics are developing at an alarming rate, portending a potential “post-antibiotic era.” In the Kearney Lab, we have developed computer algorithms that allow us to scan through genomic sequence data to pull out the antimicrobial genes from the thousands of other genes present. Thus, all the genomes across all of Life can be searched to find antimicrobial peptides that might be used as therapeutics (e.g., linoclotride), as food additives (e.g., nisin) or as transgenes that would protect crop plants or farm animals. In collaboration with Erich Baker (Baylor Computer Sciences), we have developed and patented a SVM-derived algorithm to discover sequential tri- disulfide bonded peptides (“STPs”) using only genomic sequence (Islam et al., 2015). STPs are highly useful due to their unusual stability. Going further, we have developed a universal algorithm using natural language processing. This algorithm guides the development of derivative algorithms that can be used to rapidly discover a wide variety of peptides. Now, we are able to find antimicrobial and other modulatory peptides by their function, such as identifying all of the sodium or calcium channel blocker peptides in genomic sequence. In this example, a survey of such peptides could lead to the discovery of new insecticides that can be included into the plant genome rather than sprayed, and would have no residual effect on the environment.
3) Production of targeted antimicrobial peptides in E. coli and plant expression systems
A problem with antimicrobial peptides is their broad range of action, which results in the destruction of the entire microbiome of the target organ (e.g., the gut) rather than the selective elimination of the single pathogenic bacterial species. By adding targeting domains onto antimicrobial peptides, we have created fusion peptides which specifically kill the target pathogen, leaving the commensal bacteria, essential for human health, unharmed. We are able to produce these peptides in E. coli and achieve toxicity levels against the target as high as unmodified peptides. In addition, our fusion peptides are toxic without the need to eliminate the fusion partner, reducing costs for purification and allowing the use of stable and targeted antimicrobial peptides as transgenes. We have also achieved expression of antimicrobial peptides in plants, a rarely reported achievement, and at levels much higher than the relatively few examples found in the literature. Using a bioinformatics and laboratory hybrid approach, we have determined that net charge is critical to plant expression and demonstrated commercial-level production of highly toxic antimicrobial peptides of the appropriate net charge.
4) Plant produced nanoparticle vaccines.
For Third World applications, a vaccine must be inexpensive to produce, preferably produced in Biosafety Level 1 (BSL1) conditions to further reduce costs, and stable even without cold storage. In collaboration with Alison McCormick of Touro University, California, we have produced 300 nm nanoparticle vaccines in plants in BSL1 conditions in a project funded by the Gates Foundation. These nanoparticles comprise an inner RNA core, which can replicate in human or plant cells, and a highly protective outer protein coat. They are avidly taken up by dendritic cells, the main antigen presenting cell of the human immune system. The RNA used is modified from Flock House virus, an insect virus, and the coat consists of Tobacco mosaic virus coat protein. The genes encoding these are delivered by agroinoculation to the chromosomes of intact plants, and the leaves are then harvested for nanoparticle purification a week later (Zhou et al., 2015). We have improved the nanoparticle yield by redirecting a portion of the nanoparticle assembly to the endoplasmic reticulum as well as the mitochondria (Zhou and Kearney, 2017).
Courses Currently Taught
Molecular Genetics (BIO 4306)
Biocomputing (BIO 5350)
Advanced Biocomputing (BIO 5351)
Graduate Program Director, Biomedical Studies
Chair, University Institutional Biosafety Committee
“System and Method for Identifying Peptide Sequences.” U.S. Patent Application (Serial No. 15/473,004). March 29, 2017. E. J. Baker, C.M. Kearney, S.M.A. Ashiqul Islam, and T. Sajed, Baylor University.
“Highly efficient suppressor-dependent protein expression in plants with a viral vector.” Patent number US 8,344,208. Jan. 1, 2013. C. Kearney and Z. Liu, Baylor University.
- *Ghidey M., *Islam S.M.A., *Kearney C.M. Expression of antimicrobial peptides in plants shows dependency on AMP peptide net charge. In preparation.
- *Islam S.M.A., *Kearney C.M, Baker E.J. Functional classification of cystine stabilized peptide toxins using m-NGSG model. Submitted to Nucleic Acids Research.
- *Islam S.M.A., *Kearney C.M, Heil B., Baker E.J. Protein classification using modified n-gram and skip-gram models. Submitted to Bioinformatics.
- *Zhou Y.Y,*Kearney, C.M. 2017. Chimeric Flock House virus protein A with endoplasmic reticulum-targeting domain enhances viral replication and virus-like particle trans-encapsidation in plants. Virology 507:151-160. doi: 10.1016/j.virol.2017.04.018.
- *Zhou Y.Y, McCormick, A., *Kearney, C.M. 2017. Plant Expression of Trans-Encapsidated Viral Nanoparticle Vaccines with Animal RNA Replicons. Methods in molecular biology 1499:77-86. doi: 10.1007/978-1-4939-6481-9_4
- *Zhou Y.Y., *CoxA.M., *Kearney C.M. 2017. Pathogenesis-related proteins induced by agroinoculation-associated cell wall weakening can be obviated by spray-on inoculation or mannitol ex vivo culture. Plant Biotechnology Reports (2017) 11:161–169. doi: 10.1007/s11816-017-0439-6.
- *Islam S.M.A., Sajed T., *Kearney C.M., Baker E.J. 2015.PredSTP: a highly accurate SVM based model to predict sequential cystine stabilized peptides. 2015. BMC Bioinformatics 16:210doi:10.1186/s12859-015-0633-x Editor's Pick
- *Chen Z.Y.and *Kearney C.M. 2015.Nectar protein content and attractiveness to Aedes aegypti and Culex pipiens in plants with nectar/insect associations. 2015.Acta Tropica 146:81–88.http://dx.doi.org/10.1016/j.actatropica.2015.03.010
- *Zhou Y.Y., Maharaj P.D., Mallajosyula J.K., McCormick A.A., *Kearney C.M.2015. In planta Production of Flock House virus transencapsidated RNA and its potential use as a vaccine.Molecular Biotechnology 57:325-336. DOI: 10.1007/s12033-014-9826-1
- Maharaj P.D., Mallajosyula J.K., Lee G., Thi P., *Zhou Y., *Kearney C.M., McCormick A.A. 2014.Nanoparticle encapsidation of Flock house virus by auto assembly of Tobacco mosaic virus coat protein.International Journal of Molecular Sciences 15(10):18540-56. DOI: 10.3390/ijms151018540.
*Kearney Lab members