Amy’s current research is to develop novel alternative approaches to study host-pathogen interactions using mouse embryonic stem cells (mESCs) and human induced pluripotent stem cells (hIPSCs). Specifically, she will be using mESCs or hIPSCs harbouring genetic mutations to study the functions of novel host genes during interactions with pathogens, including Salmonella and Chlamydia.
My current research involves using hIPSC to develop alternative in vitro models to study host-pathogen interactions. Specifically, I differentiate hIPSCs to macrophages to study its response to pathogens, including Salmonella and Chlamydia. To study the response of the macrophages, I use various techniques, including flow cytometry, cellular imagining (Cellomics, confocal microscopy), RNA sequencing, and proteomics. I am also using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) gene editing technology to generate genome-wide CRISPR-Cas9 knockout mutant libraries in hIPSC and immortalized cell lines to identify identify novel essential genes involved in macrophage differentiation and resistance to pathogens. Previously I optimized the method to differentiate genetically modified mESCs into functional macrophages to provide an attractive alternative resource to study host-pathogen interactions without the need for animal experimentation. I showed macrophages derived from mESCs responded to S. Typhimurium and various pathogen stimuli in a comparable manner to mouse bone marrow derived macrophages. Using a conditional homozygous mutant mouse ES cell line in the essential Traf2 gene, I showed the practically of using genetically modified ES cells to study the impact of essential genes on macrophage function.
Conditional-ready mouse embryonic stem cell derived macrophages enable the study of essential genes in macrophage function.
Scientific reports 2015;5;8908
Induced pluripotent stem cell derived macrophages as a cellular system to study salmonella and other pathogens.
PloS one 2015;10;5;e0124307
The sensor kinase CbrA is a global regulator that modulates metabolism, virulence, and antibiotic resistance in Pseudomonas aeruginosa.
Journal of bacteriology 2011;193;4;918-31
Antibiotic resistance in Pseudomonas aeruginosa biofilms: towards the development of novel anti-biofilm therapies.
Journal of biotechnology 2014;191;121-30
Mucin promotes rapid surface motility in Pseudomonas aeruginosa.
Multifunctional cationic host defence peptides and their clinical applications.
Cellular and molecular life sciences : CMLS 2011;68;13;2161-76
Therapeutic potential of host defense peptides in antibiotic-resistant infections.
Current pharmaceutical design 2012;18;6;807-19
Swarming of Pseudomonas aeruginosa is controlled by a broad spectrum of transcriptional regulators, including MetR.
Journal of bacteriology 2009;191;18;5592-602
Requirement of the Pseudomonas aeruginosa CbrA sensor kinase for full virulence in a murine acute lung infection model.
Infection and immunity 2014;82;3;1256-67