Alex Wong, Department of Biology

By Ariel Root
Bacteria were among the first life forms to appear on Earth, and can be found in virtually every corner across the planet. Some bacteria perform important roles in the environmental ecosystem, whereas others help us digest food or absorb nutrients. Still other bacteria can cause life-threatening diseases. “They’re really cool. They do different things, and do lots of things that we don’t even think or know about. It’s fascinating how they can generate so much diversity,” says ĐÓ°ÉÔ­´´ University’s Alex Wong. And then there’s the interesting issue of antibiotic resistance. A growing challenge has emerged as more bacteria are becoming resistant…a challenge that is well-worth investigating.

Alex Wong is an Assistant Professor of Biology at ĐÓ°ÉÔ­´´ University, focusing on the genetic causes and consequences of biological adaptation. He is interested both in characterizing the direct genetic targets of natural selection, and in studying the indirect effects of selection throughout the genome. “I am particularly interested in investigating the consequences of genetic interactions (epistasis) for rates and patterns of molecular evolution, and in understanding the potentially non-adaptive consequences of natural selection.” So basically, how do some bacteria become resistant to antibiotics, and what could this all mean for health and illness.

Wong’s academic career started as a mix of the hard and social sciences. Following his BA in philosophy and biology, Wong pursued a Masters of Philosophy at ĐÓ°ÉÔ­´´, establishing his ability to synthesize information, think critically, and write cohesively. Wong then studied the rapidly evolving reproductive proteins in fruit flies during his doctoral work at Cornell University, questioning the specific genetic changes that lead to character trait changes in an organism. His introduction to Psuedomonas wasn’t until postdoctoral work at the University of Ottawa, where he developed a keen interest in evolutionary observations in the lab.

While choosing a bacteria to study can be difficult, Wong describes one of his main research projects is an experimental evolutionary study of antibiotic resistance in Pseudomonas aeruginosa – a pathogen associated with inflammation and sepsis, and colonizes in organs such as the urinary tract, kidneys, or lungs. “Pseudomonas aeruginosa is a bacterium found in wet environments such as soils, bathtubs, a kitchen sink… and it’s mostly harmless.” However, the bacteria can be especially of concern for immunocompromised individuals—most notably, those with cystic fibrosis. “Because these individuals’ lungs are full of fluid, it provides the ideal breeding ground for the bacteria, … and some cells can persist despite antibiotics.” Introduction to P. aeruginosa as a teenager can result in cells that remain into adulthood, when the uniquely nutritional environment in the lungs of these individuals enables the bacteria to create colonies that can flourish. Unforeseen diminishing lung strength in these individuals is beginning to be associated with a long-ago introduction to P. aeruginosa.

Wong has explored some of the evolutionary resistance in bacterium using a variety of tools, such as the computational analysis of population genetics and comparative genomic data, experimental evolution, and molecular genetics. It’s all about “new ways to find vulnerabilities that are unique to bacteria… [some] are resistant to one or more antibiotics, while others are not vulnerable at all.”

Using the theories and practices of evolutionary biology in an applied setting related to individual care basis, or policy is what keeps Wong excited. However, in order to tackle antibiotic resistance, he acknowledges that health needs be thought of in the broader framework that considers social sciences, policy, and hard sciences. “Policy on how we use [antibiotics], to public education on antibiotics in agriculture, down to the genetics of antibiotics… the goals of the [CHAIM] Centre fit exactly with how we need to think about resistance – multi-dimensionally.”

The challenge in these investigations, Wong says, is that “things rarely work out the way we think they’re going to. It’s part of the fun, and part of the frustration,” he laughs. When thinking about resistance, Wong reiterates how important external partnerships have been with the Canadian Food Inspection Agency, University of Ottawa, and internationally.

Some of Wong’s challenges have also become his strengths. He describes times that his “favourite hypothesis is also the false hypothesis. But then,” he says, “it’s fun to figure out what is actually going on.” In fact, working with students in the lab has been particularly rewarding for Wong. Getting students into the lab, analyzing data, and fostering interest and inspiration, Wong and his students continue the journey to finding new ways to identify the unique vulnerabilities to some of the antibacterial resistances.

For Dr. Wong’s contact information, go here.

, from the Dept. of Biology, was the recipient of a CIHR New Investigators Salary Award to support his research on antibiotic resistance and bacterial adaptation. While antibiotics have been used for decades to fight bacterial infection, the evolution of antibiotic resistance has emerged as a critical public health threat. In this research, Wong will study the evolution and genetics of antibiotic resistance, and of pathogen adaptation more generally. He will use laboratory and clinical populations of infectious bacteria, including E. coli and bovine tuberculosis, to identify mutations that confer resistance or that contribute to increased fitness during infection. In addition, he has developed an innovative genetic screen that will enable him to identify novel therapeutics targeted towards antibiotic resistant pathogens.

, from the Dept.  of Neuroscience, received funding to better understand the hormonal mechanisms by which stress responses alter behavioral and metabolic processes associated with obesity. Obesity is related to a variety of pathologic conditions that include cancer, heart disease, diabetes, and renal insufficiency, all of which can lead to an early death and poor quality of life. While it is clear that there are genetic factors that are closely associated with obesity, environmental factors also play an important role. Stress, for example has been associated with a number of metabolic changes that ultimately can lead to obesity, insulin resistance, and cardiovascular disease. Interestingly, a number of symptoms that are seen following exposure to different types of stressors are also seen in animals exposed to chronically elevated levels of the hormone ghrelin. Ghrelin, a stomach derived hormone, is commonly associated with the stimulation of appetite and food intake (particularly the intake of high calorie foods), as well as the accumulation of body fat. Ghrelin appears to be released following exposure to stressors, and thus it is possible that the behavioral and metabolic alterations that are seen following chronic stress paradigms are mediated in part by ghrelin. This research seeks to provide evidence that this is the case, and to determine the parts of the brain directly affected by ghrelin to mediate these effects.

Shawn Hayley, from the Dept. of Neuroscience, was successful in acquiring funding to support his research assessing the mechanisms underlying Parkinson’s Disease. The vast majority of cases of Parkinson’s disease (PD) are of unknown origin, and environmental influences have been repeatedly implicated. That said, certain genetic changes, such as those involving a gene that appears to influence the inflammatory immune system (called LRRK2), might engender a vulnerability to the impact of environmental toxicants. In this research, it is suggested that activation of LRRK2, along with immune system messenger proteins, called cytokines, together give rise to PD. We will test this hypothesis using genetically modified mice (that either lack LRRK2 or express abnormal levels of this gene) and administering certain cytokines, immune agents (e.g. compounds that mimic viral and bacterial infections) and environmental toxicants (e.g. pesticides linked to PD).

, from the Dept. of Health Sciences, together with his research collaborator, Dr. Warren Foster of the Department of Obstetrics & Gynecology at McMaster University were awarded an operating grant to study a novel clinical marker of endometriosis. Endometriosis is an estrogen dependent disease of unknown etiology that affects between 10-15% of reproductive age women which can result in significant pain and interference with everyday activities including work and social interactions. Clinically useful markers of endometriosis are lacking and many women are symptomatic for 8-12 years before achieving a definitive diagnosis. Hence, novel clinical markers of endometriosis are urgently needed. The proposed study will investigate whether brain derived neurotrophic factor (BDNF) is a clinically useful marker of endometriosis that has the potential to offer women with pelvic pain more appropriate, effective, and less costly medical therapies compared to surgery.

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