Strategically Manipulating Bacteria for the Greater good

Lourdes Peña-Castillo is looking to understand bacteria to find ways to strategically manipulate them.

“Bacteria or, more generally, microbes are everywhere,” says Peña-Castillo, who is jointly appointed as a professor in the departments of computer science and biology at Memorial University. “They are in the house, they are in the soil, they are in the environment and they interact with everything. We know that some bacteria cause diseases, but they are a minority. All other bacteria are beneficial for plants, animals and for us.”

Given that, Peña-Castillo’s research, which she describes as being computational microbiology, applies machine learning to understand patterns in the genome of bacteria that signal to them how to “turn on” or express their genes.

“Right now, if we want to treat a disease, we basically take antibiotics and kill every single bacterium, the good ones along with the ones causing the disease,” says Peña-Castillo, who did her PhD in Computer Science in Germany and her postdoctoral work at the University of Toronto. “With my research, we are understanding in more detail every single bacterium, and then potentially we could actually either modify the gene expression of that bacterium or create treatments specifically designed for that bacterium. Instead of killing everything, let’s try to just control a specific part of a bacterium.”

She refers to this work as a foundational endeavour in “smart biotechnology,” noting that in industrial processes, for example, they sometimes want bacteria to help to create more of a certain substance.

Peña-Castillo says she couldn’t do her job without ACENET.

“In my lab, we work with collections of sequencing data,” she says. “Each raw uncompressed sequencing file can be tens of gigabytes (GBs). As each dataset can have several of these files, it can quickly add up to hundreds of GBs in disk space. Add to that the fact that the software used to process these data can easily require tens of GBs of random access memory (RAM), often at least 50, and most laptops only have 8 to 16 GBs of RAM, and you can see that ACENET is not only necessary but indispensable.”

She says her team could run a single experiment in a high-end computer, but in many cases, it runs dozens of experiments to optimize its models. 

“Using supercomputers allows us to run these experiments in parallel,” she says, adding that in one recent project her team combined more than 20 different datasets in an effort to train its models.

“ACENET enables us to do all the computational analysis that we do,” she says. “Most of my students run their calculations on ACENET, so it basically allows us to run all the experiments and analysis in an efficient way. Without ACENET, I would have to buy a lot of very expensive computers to do my job.”

Outsmarting Superbugs

The evolution of antibiotic-resistant superbugs is one of the biggest threats facing medicine today. Modern antibiotics – long the key to fighting deadly infections – have little effect on the new resistant strains of bacteria that commonly infect hospital patients who are in a weakened state. Now a Cape Breton University scientist is working with a Halifax-based drug company to develop one possible solution to this looming problem. Matthias Bierenstiel is an associate professor of inorganic chemistry and chair of the chemistry department at Cape Breton University. Much of his research involves studying and synthesizing new transition metal complexes – complex molecules that contain two metal centres. Some of the complexes he studies have been found to possess antimicrobial properties that are capable of switching off a bacterium’s resistance to antibiotics. Bierenstiel is helping to develop a way of synthesizing polymer molecules that can be used to fight drug resistant bacteria. “My area of expertise is in the binding of the iron to the polymer,” he says. There are two fundamental questions he’s trying to answer. The first is how these polymers can be manufactured to use as pharmaceuticals. The other is how exactly does the process work. “One of the questions we’re trying to answer is how the polymer wraps around iron molecules. The ACENET network gives us the computer power to model it to examine ways that it binds together. We can also use ACENET to make the next generation of compounds better.” Bierenstiel is working with Chelation Partners, a Halifax-based development stage company. that is using his research in the quest to develop a new platform of chemically synthesized chelating compounds that withhold iron from pathogens. “ACENET allows us to model the reactions without the need to go into the lab. Some runs take several weeks. Even with a supercomputer it takes a considerable amount of time.” Bierenstiel first used the ACENET system six years ago. He turned to it again last year when he began working with Chelation Partners. “My interest is in making a compound and putting it in someone else’s hands to develop and distribute,” says Bierenstiel. Bierenstiel’s research has attracted more than $2 million in equipment and operating funds over the past six years, including from the Canada Foundation for Innovation (CFI), Natural Sciences & Engineering Research Council of Canada (NSERC), Springboard Atlantic, Mitacs, Innovacorp and the National Research Council Canada (NRC).