Christopher Kearney, PI

Research Focus

We develop specialty peptides to selectively knock down pathogens and insect pests without affecting off targets. We are especially interested in large scale, low cost 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 field work funded by the B.F. Smith Foundation, we demonstrated that impatiens garden plants are highly attractive to mosquitoes and will outcompete standard garden plants in an outdoor setting for attracting mosquitoes. In work funded by the Bayer Corporation, are currently constructing our prototype transgenic impatiens plants. Future commercial production would not be an expensive, high-technology affair. Rather, impatiens are produced by cuttings, using  inexpensive, traditional plant nursery methods, suitable for adoption in Third World countries. In addition, these plants should do not harm to off target insects, unlike pesticide-based strategies.

2)  Selective knockdown of pathogenic bacteria

We have also developed peptides which specifically kill bacterial pathogens while not harming the rest of the native bacterial community. We use guide peptides that bind only to the pathogen and fuse these guides to antimicrobial peptides. We have published methods for producing these in high yield in E. coli and plants. Currently, we are working on a potential solution for dealing with the inevitable development of drug resistance by the bacteria. We have also developed a means for delivering these guided antimicrobial peptides to the gastrointestinal tract without being digested themselves by delivering the peptides via engineered probiotics. We are now able to control Helicobacter pylori infection in a mouse model using this technology. We are going further, seeking to demonstrate that any pathogen resistance developed against the guided antimicrobial peptide will result in the escape of binding by the peptide to the pathogen but also the escape of binding of the pathogen to the host cell, since the guide peptide is derived from a host receptor for H. pylori. This is the focus of our recent grant from the Cancer Prevention and Research Institute of Texas (CPRIT).  

3)  Biocomputing approaches to discover antimicrobial peptides and other modulatory peptides

My former graduate student, Mishu Islam, was  fortunate to have Erich Baker, Chair of Computer Science here at Baylor, to serve as his co-mentor, allowing him to develop 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. Mishu went further, developing a universal algorithm that 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.

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).

Patents:

“Targeted Mosquitocidal Toxins.”   U.S. Patent Application (Serial No. 15/944,285; Serial No. PCT/US2018/2590) April 3, 2018. C.M. Kearney, G.E. Pruett G.

“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.

Recent Publications:

1. *Pruett G., *Hawes J, Varnado W, Deerman H., Goddard J., Burkett-Cadena N., *Kearney C.M. 2020. The readily-transformable Impatiens walleriana efficiently attracts nectar feeding with Aedes and Culex mosquitoes in outdoor garden settings in Mississippi and Florida. Acta Tropica 210:105624. doi.org/10.1016/j.actatropica.2020.105624
2. *Choudhury, A., *Islam, S.M.A., *Ghidey, M.R., *Kearney, C.M. 2020. Repurposing a drug targeting peptide for targeting antimicrobial peptides against Staphylococcus. Biotechnology Letters, 42(2):287-294. doi.org/10.1007/s10529-019-02779-y
3. *Ghidey M., *Islam S.M.A., *Pruett, G., *Kearney C.M. 2020. Making plants into cost-effective bioreactors for highly active antimicrobial peptides. New Biotechnology 56:63-70. https://doi.org/10.1016/j.nbt.2019.12.001
4. *Zhou Y., *Ghidey M.R., *Pruett G., *Kearney C.M. 2020. The use of functionally deficient viral vectors as visualization tools to reveal complementation patterns between plant viruses and the silencing suppressor p19. Journal of Virological Methods, 286:113980. doi: 10.1016/j.jviromet.2020.113980.
5. *Islam, S.M.A., *Kearney, C.M., and Baker, E.J. 2018 Assigning biological function using hidden signatures in cystine-stabilized peptide sequences. Sci Rep 8(1):9049. doi: 10.1038/s41598-018-27177-8
6. *Islam, S.M.A., *Kearney, C.M., and Baker, E.J. 2018 Classes, databases and prediction methods of pharmaceutically and commercially important cystine-stabilized peptides. Toxins 10(6). pii: E251. doi: 10.3390/toxins10060251
7. *Islam, S.M.A., Heil, B.J., *Kearney, C.M., and Baker, E.J. 2018 Protein classification using modified n‑grams and skip-grams. Bioinformatics 34(9):1481-1487. doi: 10.1093/bioinformatics/btx82
8. *Zhou, Y.Y., and *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. http://dx.doi.org/10.1016/j.virol.2017.04.018
9. *Zhou, Y., *Cox, A.M., and *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 11:161-169. DOI 10.1007/s11816-017-0439-6
10. *Zhou, Y.Y, McCormick, A., and *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
11. *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. BMC Bioinformatics 16:210  doi:10.1186/s12859-015-0633-x Editor’s Pick
12. 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.   Acta Tropica 146 (2015) 81–88. http://dx.doi.org/10.1016/j.actatropica.2015.03.010