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.”

Deciphering the Role of the Invisible Marine Life

In terms of impact and sheer numbers, microbes dominate our planet. The tiny single-celled organisms invisible to the naked eye live everywhere on Earth – in the atmosphere, the earth’s crust and in our own bodies. The world’s oceans are also teeming with microbes – accounting for more than 90% of the ocean biomass. For Julie LaRoche, microbes represent an important indicator of the effects of climate change on ocean life. LaRoche is a biology professor and ocean scientist at Dalhousie University and the Canada Research Chair in Marine Microbial Genomics and Biogeochemistry. “We study how phytoplankton and marine bacteria are affected by increases in temperature and decreases in pH, changes that are both linked to the increase of carbon dioxide in the atmosphere. Marine microbes are key players in marine biogeochemical cycles or, simply put, they are key players in the recycling of nutrients and other elements in the ocean. Changes in the balance of the recycling will affect the productivity of the ocean, including the higher trophic life – fish and other sea creatures.” Instead of microscopes, LaRoche uses genomics and next generation sequencing techniques to study the diversity and function of ocean microbes. She says the technology has represented a huge leap forward for the science of microbiology. It has led to many discoveries of new taxonomic groups and biochemical pathways in marine microbes since its development a decade ago. LaRoche and her team have obtained the genomic sequences of microbes they have collected on ocean expeditions around the world and close to home in places such as the Bedford Basin and the Scotian Shelf. The sequences are entered into a huge database where they are analysed in the context of other oceanographic observations. As the observations accumulate over several years, the initial sequence information will serve as reference in the study the long term effects of climate change on life on Earth. “While we are discovering the roles of the microbes that live in the North West Atlantic waters, we are also establishing a baseline for comparing with the observations obtained in future studies, and assess what changes have taken place in the microbial population as a result of climate change.” Studying microbes means dealing with huge numbers. First, there are approximately 5 x 1030 microbial cells on earth representing an estimated 100 million species. The database that LaRoche and her team are working with is also huge; some 20 million sequences to date with four to five million pieces in each data set. “These are big files that take up a lot of memory. We can’t do it on a normal computer so we have to use ACENET.” LaRoche and her team have already compiled and analysed three and a half years of data using the ACENET system. The work is enabling scientists to understand the ways the world’s oceans – and life on Earth – are changing. “As the oceans continue to warm and to become more acidic, the microbial life within it may migrate closer to the poles in response,” she says. “This may affect the entire biome of the sea and that is why we need to study it.”