Q&A with the 2017 Summer Studentship Award Recipients in the Burrows Laboratory

There is no denying the issue of antibiotic resistance, which has led to cases of multi-drug resistant bacteria that are increasingly hard to combat. One such bacterium is Pseudomonas aeruginosa, an opportunistic pathogen responsible for a large numbers of morbidity and mortality in immunosuppressed individuals, including those with Cystic Fibrosis (CF). In the Burrows laboratory here at McMaster University, research is focused on understanding how the bacteria sense and respond to antibiotics, with the ultimate goal of discovering novel antimicrobial compounds.

Two undergraduate students in the Burrows laboratory were recently awarded summer studentships to continue to pursue research in this field. Richard Nguyen a 4th year Biochemistry student was awarded his second consecutive Cystic Fibrosis Summer Studentship, while Sawyer Karabelas-Pittman a 4th year Biomedical Discovery and Commercialization student received a Glyconet Summer Studentship. We had a chance to sit down and chat with these Richard and Sawyer and ask about their research and what these awards mean to them.

Q: Can you give me a short summary about your research project?
A: P. aeruginosa is a serious pathogen in people with CF and is highly resistant to many antibiotics. In response to treatment with cell wall inhibiting antibiotics (called ?-lactams) it produces AmpC (a ?-lactamase) whose function is to destroy and inactivate the antibiotic. The mechanisms leading to AmpC expression in P. aeruginosa remain incompletely understood, but are intricately linked to cell wall metabolism, specifically the peptidoglycan (PG)-recycling pathway. The functions of the major proteins in the PG-recycling pathway have been well characterized, however the structure of these proteins and whether they interact in a multi-protein complex remains unclear. The goal of my research project is to investigate and determine the interaction interfaces between these proteins.

Q: What are the real world applications of your research?
A: The ultimate goal of my research is to figure out a way to inhibit ?-lactam resistance in P. aeruginosa by preventing AmpC expression in the first place. A comprehensive understanding of the interaction interfaces among the major proteins in the PG-recycling pathway is required in order to develop new therapies and treatments. PG-recycling proteins may have interfaces that can be exploited as a drug targets using small molecule inhibitors of protein-protein interaction interfaces, a method which has seen success in other bacterial systems.

Q: What do you hope to accomplish during this time, and how will this fellowship allow you to do this?
A: This summer, I was fortunate enough to receive the Cystic Fibrosis Summer Studentship award for my second year in a row. This award will allow me to follow-up on my findings from my senior thesis in the Burrows lab, and also to expand on the scope of my project. There is so much more to be discovered about the PG-recycling pathway, and my goal this summer is to uncover novel aspects of this pathway, specifically focusing on the structures and interaction interfaces of PG-recycling proteins.

Q: Can you give me a short summary about your research project?
A: I am currently studying biofilm formation in the Gram-negative opportunistic pathogen P. aeruginosa. Biofilms are dense communities of bacteria coated in a thick substance that allows the cells to easily communicate and share resources. These biofilms also protect the bacteria and increase resistance to antimicrobials, when compared to free-floating cells. Specifically, I study the ability of the bacteria to increase biofilm formation when it is exposed to sub-lethal concentrations of antibiotics, trying to understand the key genes involved in this putative response pathway. I am also conducting a high throughput screen of ~4000 bioactive compounds, testing for molecules able to inhibit biofilm formation.

Q: What are the real world applications of your research?
A: This year, the World Health Organization listed P. aeruginosa as a priority pathogen, highlighting the need for new antimicrobials against this bacterium. The high throughput biofilm assays that I am conducting, has the potential to uncover new antimicrobial compounds to be used against this bacteria. Additionally some compounds may be able to prevent biofilm formation, which in combination with existing antibiotic therapies could boost the efficacy of these drugs.

Q: What do you hope to accomplish during this time, and how will this fellowship allow you to do this?
A: The GlycoNet Summer Studentship has afforded me the opportunity to fully commit my summer to research, allowing me to advance my project further than would have otherwise been possible. It is my goal this summer to validate the preliminary results that I’ve gathered during my thesis, which entails both understanding the genes involved in the antibiotic-mediated biofilm stimulation response, as well as follow up assays on compounds identified by the high throughput bioactives screen.

Both Richard and Sawyer have finished up their undergraduate degrees at McMaster University, and will be moving on to tackle new challenges come September. Richard has been accepted to the University of Toronto Faculty of Dentistry, and hopes to become a dentist-scientist, putting his research skills to use in this field. Sawyer will be working towards his Masters degree in Biomedical Discovery and Commercialization here at McMaster University, and will make his passion for science into a career in the future.