Year: 2020

Gastrointestinal (GI) infection caused by the bacterium Clostridioides difficile is a common complication of inflammatory bowel disease (IBD), a condition caused by an aberrant host immune response to the GI microbiota. C. difficile infection (CDI) typically occurs after disruption of the GI microbiota, making the immune response to microbiota during IBD a major risk factor. This is particularly important in pediatric populations where 47% may suffer from an IBD-CDI co-occurrence. Fecal microbiota transplant (FMT) is a successful experimental treatment for IBD and CDI. It is thought to work by restoring a healthy-functioning microbiome to the IBD-CDI patient, however the specific host and bacterial factors that define FMT’s success remains unknown. We will recruit pediatric IBD-CDI patients to define host immune responses to FMT treatment. Using a novel IBD-CDI mouse model, we will then attribute host responses to FMT therapy and microbiota composition. This translational research will advance our mechanistic knowledge of FMT efficacy and ultimately impact FMT safety and governance. We will present our findings at international conferences including Canadian Digestive Diseases Week and aim to publish them in high-impact journals.

Cystic fibrosis (CF) is a rare hereditary condition where patients experience frequent chest illnesses (exacerbations), resulting in a decline in lung health and premature death. Typically, exacerbation symptoms include an increase in cough and phlegm, with an accompanying decline in lung function. Up to half of all persons with CF (PWCF) require at least one course of intravenous antibiotics to manage their exacerbations each year, but at least 25% will not recover to their original lung function after treatment. While it is clear that not all chest illnesses in PWCF occur due to bacterial infections, we are unable to identify other causes when diagnosing a patient. Consequently, PWCF receive antibiotics in almost all instances of chest illness, even when bacteria may not be the cause, exposing these patients to unnecessary harm. This study will involve analysis of blood and phlegm samples from >100 PWCF to identify clinical and molecular markers that can indicate the cause of an exacerbation. Through the use of sophisticated statistical techniques, we will then develop a tool that can be used to predict exacerbation cause and allow physicians to select treatments that are more specific, appropriate and beneficial for patients.

In the modern pharmaceutical industrial, a large number of new drug candidates come from molecules isolated from microbes. These “natural products” include some of our most powerful antibiotics, chemotherapeutics, and other medicines. Unfortunately, investment into natural-product drug discovery has declined since the turn of the century, owing to the high chance of re-discovery of known molecules. However, advances in bioinformatics suggest that the number of potential new drugs available from microbes is enormous. To advance the field of natural product drug discovery and exploit these advances in bioinformatics, we are developing a creative method to discover natural products with specific chemical sub-structures, which have a high probability to become drug candidates. This method is a biosynthetically-inspired, genome-mining technique that employs 15N-NMR as a key technique. Our initial work has resulted in a structurally unprecedented molecule, together with a yet-unknown molecule with exceptional antibiotic activity against gram-negative pathogens. Here we propose to extend our approach for the targeted isolation of additional molecules, followed by assessment of their pharmaceutical properties for preclinical testing.

Mosquitoes are the world’s deadliest animals due to the pathogens they spread and are often highly invasive. Arboviruses (arthropod-borne viruses) are spread by arthropods such as mosquitoes, and frequently infect both human and animal hosts. Multiple mosquito-vectored arboviruses have spread to new regions recently, including West Nile virus and Zika virus. While the mode of introduction is often unknown, the movement of infected mosquitoes or infected animal hosts are believed to be two of the methods responsible.

East Asia is an area from which arboviruses and mosquito vectors are at increasing risk of introduction to BC. I will survey the distribution of mosquitoes that vector established arboviruses in BC, or that could serve as vectors for arboviruses at risk of emerging in BC, particularly in northern and rural regions. I will use machine learning to model the distribution of these species now and in future climate change. What makes a mosquito species likely to be invasive will be studied using genomics, ecology, and cutting-edge behavioural techniques. Once these traits are known, I will model potential habitat in BC of candidate species from east Asia that could  become invasive in BC.

Lungs are constantly exposed to environmental challenges, making them susceptible to infection and injury. For this reason, they are protected by specialized cells that can respond rapidly to danger signals. Amongst these cells are innate lymphoid cells (ILCs) that include three main subsets: group 1, group 2 and group 3 ILCs. To date, the majority of the studies have focused on ILC2s and their importance in allergy and tissue repair. However, it is now becoming evident that ILC3s play a key role in lung health. In fact, ILC3s have recently been shown to accumulate in the lung after Mycobacterium tuberculosis infection and in an obesity-induced asthma disease. Accordingly, preliminary results show that the accumulation of ILC3s in the lung is mediated by IL-1b, yet the mechanisms inducing ILC3s in the lung and their function remain unclear. This project will provide an extensive analysis of the origin and functions of ILC3s in naive and inflamed lungs, with an ultimate goal of translating our findings to a wide range of lung diseases, which are life-limiting and still a major cause of death in young, elderly, immune-compromised and cystic fibrosis patients.

There is evidence in North America that people who have a developmental disability (DD) are living longer due to improved health care for high risk babies and children and to increases in longevity in general.  However, in BC there is nothing known about the lifespan, health and health care usage of these individuals.  The health of people who have a DD as they transition from child health care services (often pediatricians) to adult health care services (often family physicians) may be of particular concern.  Pediatric services may offer more specialized knowledge and longer appointments which support the health of people with complex medical conditions.  This specialized support may no longer be available as people with a DD transition to adulthood.   

This study will use population- level administrative health data from Population Data BC to examine health care usage of people with a DD who are transitioning from child to adult health care services.  Information gained from this study will be used to increase understanding of current health care needs and planning for future health care for this vulnerable population.