- Postdoctoral Fellow, Tufts University, 2011-2015
- Ph.D., University of Pennsylvania, 2011
Assistant Professor, Biology
Assistant Professor, Biology
Jordan Hall 455
Microbes can rapidly adapt and evolve in the face of clinical interventions and environmental insults. One mechanism that promotes this evolution is horizontal gene transfer (HGT) through natural competence and transformation. During this process, microorganisms take up DNA from the extracellular environment and integrate it into their genome by homologous recombination. Natural transformation is a property of diverse microbial species and is often tightly regulated. In our lab, we study the mechanisms and regulation underlying this conserved evolutionary process.
One model organism we employ to study natural transformation is Vibrio cholerae - the causative agent of the diarrheal disease cholera. This pathogen naturally resides in the aquatic environment and causes disease when ingested in contaminated food or drinking water. In the environment, V. cholerae forms biofilms on the chitinous exoskeletons of crustacean zooplankton, which is critical for both the survival and waterborne transmission of this pathogen. Chitin also induces natural competence in this organism. In our lab, we are studying the mechanisms and regulation of Vibrio-chitin interactions to gain insight into how V. cholerae evolves in the aquatic environment and transitions from this site to infect its human host. It was recently found that clinical isolates of V. cholerae are poorly transformed by this mechanism of HGT. So, we are also studying natural transformation in clinical isolates of V. cholerae to determine the mechanisms and role of HGT in strains from the ongoing 7th pandemic of cholera.
In addition to studying mechanisms of HGT, we have also exploited this process to develop a novel method for multiplexed genome editing by natural transformation (MuGENT). This method allows for "accelerated evolution" of microbes through the integration of multiple unlinked fragments of DNA into the bacterial genome in a single step. This increases the pace of genetic studies, but also allows us to probe biological questions that were previously genetically intractable. We are currently employing this method to dissect the biology of bacterial pathogens, including V. cholerae. MuGENT also allows for rapid metabolic and phenotypic engineering of microbes, which we will employ to develop non-pathogenic naturally competent species for novel biotechnology applications.
We use genome-wide approaches (Tn-seq, RNA-seq, ChIP-seq, etc.), comparative genomics, genetics, molecular biology, microscopy, flow activated cell sorting (FACS), and biochemistry to achieve these goals.
Dalia TN, Yoon SH, Galli E, Barre FX, Waters CM, Dalia AB*. Enhancing multiplex genome editing by natural transformation (MuGENT) via inactivation of ssDNA exonucleases. Nucleic Acids Res. 2017 May 31. doi: 10.1093/nar/gkx496.
Klancher CA, Hayes CA, Dalia AB*. The nucleoid occlusion protein SlmA is a direct transcriptional activator of chitobiose utilization in Vibrio cholerae. PLoS Genet. 2017 Jul 6;13(7):e1006877.
Dalia AB*. RpoS is required for natural transformation of Vibrio cholerae through regulation of chitinases. Environ Microbiol. 2016 Nov;18(11):3758-3767.
Dalia TN, Hayes CA, Stolyar S, Marx CJ, McKinlay JB, Dalia AB*. Multiplex Genome Editing by Natural Transformation (MuGENT) for Synthetic Biology in Vibrio natriegens. ACS Synth Biol. 2017 Jun 6. doi: 10.1021/acssynbio.7b00116.
Hayes CA, Dalia TN, Dalia AB*. Systematic genetic dissection of chitin degradation and uptake in Vibrio cholerae. Environ Microbiol. 2017 Jul 28. doi: 10.1111/1462-2920.13866.
Hayes CA, Dalia TN, Dalia AB*. Systematic genetic dissection of PTS in Vibrio cholerae uncovers a novel glucose transporter and a limited role for PTS during infection of a mammalian host. Mol Microbiol. 2017 May;104(4):568-579.
Dalia AB, Seed KD, Calderwood SB, Camilli A. A globally distributed mobile genetic element inhibits natural transformation of Vibrio cholerae. PNAS. 2015 Aug 18;112(33):10485-90.
Dalia AB, McDonough E, Camilli A. Multiplex genome editing by natural transformation. PNAS. 2014 Jun 17;111(24):8937-42.