Josephine (Josie) Chandler


Josie Chandler
  • Associate Professor

Biography

The focus of my laboratory research is on bacterial social behaviors that have important contributions to communities found in infections, natural ecosystems and synthetic microbial communities. Throughout my career I have studied a range of bacterial social behaviors including cooperation, competition and communication. Research in this area consistently intersects biology and chemistry and leverages emerging tools in genetics and genomics and “reductionist” models of synthetic microbial communities to uncover new insights into bacterial social behavior.

I attended the University of Iowa for my undergraduate degree (2000). I earned my Ph.D. (2006) at the University of Minnesota under the mentorship of Dr. Gary Dunny. I then moved to the University of Washington to carry out my postdoctoral studies with Dr. E.P. Greenberg. In 2012, I transitioned to a Research Assistant Professor at the University of Washington and in 2013 I began my faculty position at KU.

I am currently an Associate Professor in Department of Molecular Biosciences at the University of Kansas. I am also an affiliate of the Department of Ecology and Evolutionary Biology. I am the co-PI of the KU Bridges to Baccalaureate Research Training Program and shared the student-nominated KU Honor for Outstanding Progressive Educator (HOPE) award in 2022 with Dr. Eileen Hotze (also a member of Molecular Biosciences).

Education

B.S. in Microbiology (minor in Sociology), University of Iowa, 2000
Ph.D. in Microbiology, Immunology and Cancer Biology, University of Minnesota, 2006
Postdoc (quorum sensing / Burkholderia thailandensis), University of Washington, 2012

Research

Research overview

Most bacteria are found in complex microbial communities, where social interactions between community members shape community function and composition. Bacterial interactions play a dramatic role in shaping the composition and function of natural microbial communities, for example those found in infections, soil and plant roots and synthetic systems used for fermentation and bioremediation. There has been great progress in understanding the molecular mechanisms of social behavior. Results of those studies have been useful to elucidate the molecular biology of quorum sensing but provide a limited understanding the role of these social interactions in more complex communities such as those from the environment and infections.

A combination of new technologies in genomics and genetics and the development of laboratory
models or ‘synthetic ecology’ approaches provide new opportunities to study bacterial interactions. The laboratory models offer a powerful but simplified approach to study reductinist multiple-strain and multiple-species communities in a controlled setting. These synthetic communities offer many advantages over direct studies of natural communities, which can present many challenges. We focus our studies on several species of Proteobacteria such as Burkholderia pseudomallei, the causative agent of melioidosis, the soil bacterium Chromobacterium subtsugae and Pseudomonas aeruginosa, an opportunistic pathogen and the most common cause of fatality in patients with the genetic disease cystic fibrosis.

Cell-cell communication

Many bacteria communicate using small chemical molecules or ‘signals’ that transmit messages between cells. One of the mechanisms by which bacteria communicate is quorum sensing. Quorum sensing is a type of cell-cell signaling that regulates behaviors in a population density-dependent manner. Quorum sensing contributes to pathogenesis of many plant and animal pathogens and for this reason has been the target of efforts to develop novel antivirulence therapeutics. My work is broadly focused on how quorum sensing systems benefit bacteria in multispecies communities. We have shown that quorum sensing coordinates the production of toxins, which can be important for interspecies competition. We have also shown that quorum sensing controls antibiotic resistance, which can defend against competitors during competition. We are leveraging our laboratory models to understand how quorum sensing control of toxins and toxin resistance impacts the dynamics of competition. We are also interested in understanding how antibiotics contribute to the evolution of quorum sensing.

Antibiotic discovery

Many bacterial toxins are quorum sensing-controlled, such as the antibiotic bactobolin produced by B. thailandensis and hydrogen cyanide produced by P. aeruginosa. We are interested in understanding how bacteria use quorum sensing to coordinate production of these toxins and to compete with other strains and species. We are also interested in the chemistry and biology of these molecules, which are an important yet understudied facet of survival and pathogenesis of many soil microbes. Our work on antibiotics began with bactobolin, a potent, broad-spectrum antibiotic produced by B. thailandensis. We have since focused on other antibiotics – specifically, malleilactone, and more recently 4-hydroxy-3-methyl-2-alkylquinoline antibiotics, produced by B. thailandensis. We are also carrying out studies of hydrogen cyanide produced by P. aeruginosa and C. subtsugae.

Cooperation

Quorum sensing commonly regulates cooperative behaviors. Cooperative behaviors involve public goods that can be shared by all of the members of a population, including those that do not produce it. Public goods are available to everyone (an excellent example of a public good is National Public Radio). Those individuals that pay for the public goods are called cooperators. Those that utilize the public goods without paying are called cheaters. In the case of NPR and other true public goods, a certain number of cooperators are required to maintain production of the public good - if there are too many cheaters, the system will fail. In bacteria, common examples of public goods include extracellular factors such as proteases or antibiotics, or extracellular matrix material that holds a biofilm together. In bacteria these public goods are commonly regulated by quorum-sensing systems. We have contributed to the emerging idea that quorum sensing can stabilize cooperation through mechanisms of cheater restraint. We are also studying how cooperators and cheaters are involved in an evolutionary arms race where they continually improve their ability to compete with one another. Studies of bacteria offer a window into understanding cooperation in a broader sense and also the opportunity to observe the evolution of sociality in real time.

Teaching

  • BIOL518 - Bacterial Genetics (undergraduate - Fall)
  • BIOL815 - Advanced Bacterial Genetics (graduate - Spring)
  • BIOL599 - Microbiology Senior Seminar (Spring/Fall)

My classroom teaching primarily includes teaching bacterial genetics (BIOL518 and BIOL815), as well as microbiology senior seminar (BIOL599). I also guest instruct in the Chemical Biology (BIOL860) and Responsible Conduct of Research (BIOL817) courses. In my teaching I use a combination of active learning, lecturing and project work and assessment tools that cater to a variety of learning styles.

Outside of the classroom, I mentor and train junior scientists to conduct research in my NIH-funded laboratory. I am lucky to have worked with many exceptionally talented undergraduate, graduate and postdoctoral trainees especially during a time when scientific training has taken on a new level of importance in our society. I am also involved in several efforts to make science and scientific training more inclusive. I am the co-PI on the NIH-funded Bridges to Baccalaureate program to help Native students bridge from Haskell University to KU in biomedical career tracks. I am also the chair of the Molecular Biosciences committee on diversity, equity, and inclusion and a member of the KU council on disabilities.

Selected Publications

  • Loo C, Koirala P, Smith NC, Oller A, Evans K, Benomar S, Parisi IR, Chandler JR. Cross-species activation of hydrogen cyanide production by a promiscuous quorum-sensing receptor promoters Chromobacterium subtsugae competition in a dual-species model. bioRxiv 2022.11.01.514797 (in revision at Microbiology)
  • Spencer P, Ye Q, Misra A, Chandler JR, Cobb CM and Tamerler C (2022) Engineering peptide-polymer hybrids for targeted repair and protection of cervical lesions. Front. Dent. Med 3:1007753. doi: 10.3389/fdmed.2022.1007753. Review.
  • Abisado RG, Kimbrough JH, McKee BM, Craddock VD, Smalley NE, Dandekar AA, Chandler JR. 2021. Tobramycin adaptation enhances policing of social cheaters in Pseudomonas aeruginosa. Appl Environ Microbiol AEM. 87(12):e0002921, doi: 10.1128/AEM.00029-21 [Selected for AEM Editor’s Pick]
  • Klaus JR*, Majerczyck C*, Moon S, Eppler MA, Smith S, Tuma E, Groleau MC, Asfahl KL, Smalley NE, Hayden HS, Piochon M, Ball P, Dandekar AA, Gauthier C, Dèziel E, Chandler JR. 2020. Burkholderia thailandensis methylated hydroxy-alkylquinolines: biosynthesis and antimicrobial activity in co-cultures. Appl Environ Microbiol 86(24):e01452-20. PMCID: PMC7688213, doi: 10.1128/AEM.01452-20.  *Shared first author. [Selected for AEM Editor’s Pick]
  • Benomar S, AM Bender, BR Peterson, JR Chandler*, BD Ackley*. 2020. The C. elegans CHP homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen. PLoS Pathogens. 6(1):e1008134. doi: 10.1371/journal.ppat.1008134. PMCID: PMC6952083. *Co-corresponding authors. [Featured in KU News]
  • Soldano A, Yao H, Chandler JR, Rivera M. 2020. Inhibiting iron mobilization from bacterioferritin in Pseudomonas aeruginosa impairs biofilm formation irrespective of environmental iron availability. ACS Infect Dis 6(3):447-458. doi: 10.1021/acsinfecdis.9b00398. PMCID: PMC7076691.
  • Slinger BL, JJ Deay, JR Chandler, HE Blackwell. 2019. Potent modulation of the CepR quorum sensing receptor in a Burkholderia cepacia complex member using non-native N-acyl homoserine lactones. Sci Rep. 9(1):13449. doi: 10.1038/s41598-019-49693-x. PMCID: PMC6748986.
  • Benomar S, KC Evans, R Unckless and JR Chandler. 2019. Efflux pumps in Chromobacterium species increase antibiotic resistance and promote survival in a co-culture competition model. Appl Environ Microbiol. PMID: 31324628. PMCID: PMC6752006.
  • Klaus JR, JJ Deay, B Neuenswander, W Hursh, Z Gao, T Bouddhara, T Williams, J Douglas, K Monize, P Martins, C Majerczyk, M Seyedsayamdost, B Peterson, M Rivera and JR Chandler (2018). Malleilactone is a Burkholderia pseudomallei virulence factor regulated by antibiotics and quorum sensing. Journal of Bacteriology 200:e00008-18. PMID: 29735757 PMCID: PMC6018353.
  • Evans KC, S Benomar, LA Camuy-Vélez, EB Nasseri, X Wang, B Neuenswander and JR Chandler.  2018. Quorum-sensing control of antibiotic resistance stabilizes cooperation in Chromobacterium violaceum. The ISME J 12:1263. PMID: 29374267. PMCID: PMC5932061.
  • Eshelman K, H Yao, AN Punchi Hewage, JJ Deay, JR Chandler and M Rivera. 2017. Inhibiting the BfrB:Bfd interaction in Pseudomonas aeruginosa causes irreversible iron accumulation in bacterioferritin and iron deficiency in the bacterial cytosol. Metallomics 9:646. PMID: 28318006. PMCID: PMC5494978.
  • Tseng BS, CD Majerczyk, D Passos da Silva, JRChandler, EP Greenberg EP and MR Parsek. 2016. Quorum sensing influences Burkholderia thailandensis biofilm development and matrix production. J Bacteriol JB.00047-16. PMID: 27068594. PMCID: PMC5019063.
  • Wang X, K Hinshaw, S Macdonald and JR Chandler. 2016. A draft genome sequence of Chromobacterium violaceum strain CV017. GenomeA e00080-16. PMID: 26941151. PMCID: PMC4777762.
  • Truong TT, M Seyedsayamdost, EP Greenberg and JR Chandler. 2015.A Burkholderia thailandensis acyl-homoserine lactone-independent LuxR homolog that activates production of the cytotoxin malleilactone. J Bacteriol 197:3456. PMID: 26941151. PMCID: PMC4777762. [F1000 Recommended]
  • Smalley NE, D An, M Parsek, JR Chandler* and A Dandekar*. 2015. Quorum sensing protects Pseudomonas aeruginosa against cheating by other species in a laboratory co-culture model. J Bacteriol 197:3154. PMID: 26195596. PMCID: PMC4560282.  *Co-corresponding authors
  • LaFayette S, D Houle, T Beaudoin, G Wojewodka, D Radzioch, L Hoffman, J Burns, A Dandekar, N Smalley, JR Chandler, J Zlosnik, D Speert, J Bernier, E Matouk, E Brochiero, S Rousseau and D Nguyen. 2015. Cystic fibrosis-adapted Pseudomonas aeruginosa quorum sensing lasR mutants cause hyper-inflammatory responses Science Adv 1: e1500199. PMID: 26457326. PMCID:  PMC4597794.