Infectious diseases as shown by the COVID-19 pandemic, remains a serious threat. Genomic sequencing has revolutionized the detection and characterization of pathogens for surveillance and outbreak investigation, creating the new field of genomic epidemiology. During this ongoing pandemic, we have witnessed several gaps in establishing effective global responses that require coordinated action such as our ability to quickly adapt analytical methods to new pathogens and the ability to integrate several data sources to generate knowledge for enabling evidence-informed decision making. In this proposed research, I aim to further this field of genomic epidemiology by developing advanced data analysis methods. Additionally, I aim to optimize these methods to be capable of adapting to datasets from various pathogens, saving time to develop again for every outbreak. Finally, I want to combine genomics and advanced data analysis (bioinformatics) to establish a method of integrating epidemiological, political, and other contextual information with genomic data to improve public health preventive measures. This project will develop a program to use intersectoral genomic epidemiology for countering infectious diseases.
Research Location: Simon Fraser University
Fine-scale mapping of high dimensional brain imaging genetics
Brain imaging genetics looks at how differences in genes (the part of our DNA that makes us who we are) affect our brains. The connections between different parts of the brain, and the way the brain develops are all influenced by genes. Usually, when scientists look for genetic effects in the brain, they look for really broad characteristics such as the the sizes, or thicknesses of the different parts of the brain. This is useful for giving us a big picture about what’s happening, but it hasn’t led to any deep understanding of genetic neurodegenerative diseases (instead, it provides more of a description rather than an understanding). The main tool for measuring the brain in humans is magnetic resonance imaging (MRI). The MRI produces a three dimensional picture of the brain. The “pixels” of the picture are known as voxels (as they are volumetric). There are many voxels in each MRI picture, and the complexity and size of the picture is the reason scientists have so far only looked at broad effects. By using modern machine learning and statistical techniques, the challenge of looking for genetic effects at the level of the voxel can be overcome.
Alternative approaches to the criminalization of drugs: A drug policy research program for BC
The criminalization of drugs contributes to a range of health and social harms for people who use drugs (PWUD) across BC and Canada. Criminalization is a barrier for PWUDs access to health and harm reduction services. It also increases overdose and infectious disease risk and contributes to the over-incarceration of PWUD in Canadian prisons. The harms from criminalization are increasingly recognized by policymakers, scholars, and advocates across Canada. In BC, alternative policy models are being considered, including depenalization, decriminalization, police diversion, and safer supply programs. There is a timely opportunity to investigate the decisions, policies, and interventions related to these alternative approaches that aim to promote health equity for PWUD. This community-engaged research program will engage, work closely with, and gather the views of policymakers, health and justice system actors, PWUD, and other communities impacted by illicit drugs, to ensure the relevance, usefulness, and applicability of findings. Knowledge gained from this research is vital to support and promote health equity for PWUD both in BC and beyond.
Mental health needs and technological interventions for social connectedness amongst older adults
Health Research BC is providing match funds for this research project, which is funded by a Social Sciences and Humanities Research Council (SSHRC) Connection Grant.
Older adults are one of the most at-risk groups in the COVID-19 pandemic, both to the negative effects of the virus and on their social connections. In order to stop the spread of COVID-19, social distancing and stay-at-home orders have been put in place. As a result of these steps, places that older adults go to socialize, for example seniors’ community centres, have been forced to close. The aim of this project is to work with a not-for-profit community centre, the West End Seniors Network (WESN), to disseminate the finding from a project where we examined the social connectedness of seniors during the COVID-19 pandemic. The mission of WESN is to enhance the quality of life of older adults by providing social, recreational, educational and supportive programs and services that foster connection and inclusion in the broader community. WESN is the second-largest independent seniors’ centre in Vancouver with over 900 active members; however, due to COVID-19 WESN was forced to close its doors. Through this project we will work with WESN staff and community members to disseminate ways that we can develop stronger social connections. Through interviews with staff, community members, and older adults, we identified what worked, and what did not work to better seniors COVID-19 experience. We will use this information to inform policy-makers, other community centres, and older adults of the ways that we can improve social connections during the pandemic. Through this project we can use the lessons learned and relationships built in this project in larger programs and with more partners.
Adapting breath/air communications to rural, remote and Indigenous ways of living
Health Research BC is providing match funds for this research project, which is funded by a Social Sciences and Humanities Research Council (SSHRC) Connection Grant.
Breathing is living. In recent years, policies that impact lung health and air quality have led people to change how they go about daily life. Traditionally, these policies are crafted by experts and specialists, with little input from the public. More effective policies could be developed by enhancing public participation and collaboration in the policy process. The overarching goal of our work is to improve the sharing and exchange of information about lung health policies with people living in rural, remote, and Indigenous communities.
This study uses design methods to adapt lung health policy communications for rural, remote, and Indigenous communities. The connections we create will be facilitated by two streams of outreach activities:
Stream 1 — AIRWISE-CONNECT — creates a community advisory group with Indigenous and non-Indigenous community members in northern British Columbia. This group will meet four times over a year to participate in a human-centred design process and interactive group meetings. During these meetings, we will adapt a previously developed website: www.airwisebc.ca.
Stream 2 — AIRWISE-VISION — develops a working relationship with the Witset First Nation Band Council and community members to better inform policies and practice. We will draw on the Design Justice method to create new breath/air policy communications that honour the traditional knowledge and practices in Witset.
The principal investigator, Sonya Cressman, a health economist at Simon Fraser University and the Centre for Clinical Epidemiology and Evaluation, will lead the study with co-Investigators: Brian Fisher and Dawn Hoogeveen at SFU and collaborators: Renelle Myers (BC Cancer), Anthony Noonan (Executive Director, Witset First Nation), Anne- Marie Nicol (SFU), and Chris Carlsten (Legacy for Airway Health).
General and inexpensive saliva-based viral RNA testing by direct imaging
This award is co-funded by Health Research BC, through CIHR’s Operating Grant: COVID-19 Rapid Research Funding Opportunity – Diagnostics.
In the absence of a vaccine and/or effective treatment, rapid and robust testing is vital not only to reduce the transmission and spread of SARS-CoV-2, but also for paving the way to safely reopen borders and reinstating the world economy. Most Covid-19 tests are performed using nasopharyngeal swabs that are sent to a hospital or public health laboratory to be processed for RT-PCR analysis using expensive equipment by technically trained staff. The specificity of such amplification-based tests makes them superior to many other detection tests. However, the occurrence of false-negative results due to the low levels of viral RNA found in such samples, as exemplified by recent problems with Spartan Cube1, suggests that avoiding nucleic acid amplification entirely and switching to the direct detection of viral RNA could be highly advantageous for SARS-CoV-2 detection.
Dr. Peter Unrau is leading a team of researchers to develop a new saliva-based viral testing strategy for use in the current Covid-19 pandemic. Dr. Unrau (professor in RNA biochemistry) and co-investigator Dr. Forde (professor in biological physics) will coordinate a research team at Simon Fraser University. They will work in collaboration with David Rueda, a professor in single-molecule imaging at Imperial College London.
This COVID-19 research will allow the development of a fast, inexpensive and sensitive viral RNA test that, in principle, could be used for point of care testing at home. The proposed SARS-CoV-2 RNA single-molecule imaging test will be highly specific, will rely on simple well-understood chemistry, and will include an inexpensive imaging device that connects to a cell phone. An additional benefit of this device is that test procedures can easily be adapted for the screening of other RNA pathogens in the future.
End of award update – January 2022
Most exciting outputs
We have developed a prototype device able to test for viral pathogens in spit. This device can report results easily over the internet and has many potential rapid testing applications.
Impact so far
Reliable and inexpensive point of care diagnostic technology is extremely important during a pandemic for both primary and community health care. As can be seen with the explosive spread of the Omicron coronavirus variant, RT-PCR test centers are overwhelmed and there is no coherent way to report point of care test results to centralized government agencies. We have developed an inexpensive (< $100 if mass produced) point of care instrument that via the internet can simply and reliably report test results to centralized data centers. This device accepts modular test cartridges, which could, with further development, offer a broad range of test services at low cost. Such a device has many uses, but could easily be imagined to play an important role in rural and remove health care locations in the future. While now only a proof of principle prototype, future investment should result in a device able to provide a health benefit to BC citizens.
Potential future influence
Inexpensive point of care tests are difficult to develop and implement. Our device offers a potential solution to this global problem.
We are seeking further investments by third parties to commercialize our prototype technology.
- Laboratory website: https://www.rnabiochemistry.com/
Automated body composition analysis for precision medicine applications
There is growing evidence showing that the amount of muscle and fat one has in the body influences various aspects of cancer such as carcinogenesis (formation of cancer), response to chemotherapy drugs (to decide on the optimal dosage to the patient to destroy cancer cells while avoiding damage in other organs), death resulting from complications due to surgery, and overall survival outcomes. Conversely, cancer also causes loss of muscle mass. Accurate and easily available tools are thus needed to measure muscle and fat in an individual in the context of cancer treatment decisions. CT images are almost universally acquired in cancer diagnosis and treatment planning, and these directly show muscle and fat in the body. But in order to extract measurements, manual intervention (which is tedious) or automated tools are needed. We are developing a fully automated 3D method to measure the amount of muscle and fat from 3D CT images available in the cancer clinic. The availability of these measurements will enable correct chemotherapy treatment dosage to be determined for each individual based precisely on their body composition, resulting in better health outcomes.
Multispectral RNA Mango: Synthesis of new multicolour fluorogens for incorporation into pathogen detection and identification kits
With the increasing prevalence of viral pathogens as exemplified by COVID-19, reliable and inexpensive detection is of increasing importance. Rapid testing allows appropriate and immediate treatment, which can have a profound effect on the treatment outcome. Early on-site detection is also greatly beneficial for hospitals and clinics since it would allow patients to be rapidly screened before entering the system.
Viruses and bacteria contain unique RNA fingerprints that can be used to identify their exact species. Recently, we have developed RNA Mango technology that can specifically and rapidly detect extremely low levels of RNA and that outcompetes the previous standard for RNA-based pathogen detection (RT-PCR) in terms of speed, while maintaining sensitivity. A limitation of our current technology is that it is not yet as reliable as it needs to be, since it is lacking controls for reaction failure — an important aspect for pathogenic detection and identification. In this application, we will further develop our RNA-detection technology into a rapid, multichannel, colour-based test that will allow us to quickly and reliably detect and identify multiple pathogens and expand its commercial in vivo applications.
Fucosylation inhibitors for convenient production of fucose-deficient antibodies
Therapeutic antibodies have revolutionized the treatment of cancers. The efficacy of many of these antibodies depends on their ability to recognize and bind to cancer cells. These antibodies then recruit immune cells to kill the cancer cells. Recent interest has focused on the different sugar molecules attached to the antibody and their role in helping or hindering the recruitment of immune cells. Specifically, eliminating one specialized sugar known as fucose from antibodies dramatically improves their ability to recruit immune cells and kill cancers. Industry is therefore interested in ways to prevent this sugar modification and to thereby produce improved anti-cancer antibodies.
We have developed a new family of chemical compounds that block the addition of fucose onto antibodies as they are being produced. We now aim to translate this work to drive the generation of improved therapeutic antibodies. Because the fucose-deficient antibodies are much more potent, it is expected that lower doses of these antibodies can be used leading to a lowered risk of side effects. Additionally, the increased potency should lead to improved efficacy of therapeutic antibodies and outcomes for cancer patients in British Columbia and elsewhere.
Design and evaluation of an evidence-based exercise program to enhance protective responses for avoiding fall-related traumatic brain injury in older adults
Falls cause up to 80% of traumatic brain injuries (TBI) in older adults. Any fall from standing may cause TBI if head impact occurs. Humans use movement strategies to avoid head impact during falls, such as 'arresting' the fall with the arms. Through video capture of real-life falls, we found that these strategies persist but become less effective for older adults in long-term care, with over 1/3 of falls resulting in head impact in this setting. This project continues our work with Debbie Cheong (Osteofit Provincial Coordinator at BC Women's Health Centre) to design and evaluate novel exercise programs for enhancing protective responses for avoiding head impact in falls. We will identify the strength and flexibility demands of common safe landing strategies observed in falls in older adults, and design and evaluate feasible approaches to enhance those capacities for older adults of varying physical and cognitive status.
This project will lead to new evidence on the strategies that older adults use to avoid head impact during falls, and the musculoskeletal demands of those strategies; new exercise-based approaches for targeting and enhancing the effectiveness of fall protective responses in older adults; and evidence of the feasibility and effectiveness of our exercise program for older adults.