Characterising the cellular response of neurons and astroglia to infection by non-polio enteroviruses
Enterovirus infections cause half the clinical cases of aseptic meningitis. Enteroviruses, single-stranded positive-sense RNA viruses of the family Picornaviridae, are associated with illnesses including hand, foot and mouth disease, myocarditis, encephalitis and acute flaccid paralysis. Poliomyelitis is caused by three serotypes of enterovirus, but several non-polio enteroviruses also cause neurological disease. Outbreaks of Enterovirus D68 in 2014, 2016 and 2018 were associated with acute flaccid myelitis and these new strains are able to replicate in human neuroblastoma cell culture. Echovirus 6 has also shown increased neurovirulence since 2016. Due to a lack of understanding of enterovirus pathogenesis, there are currently no effective specific therapies for any non-polio enteroviruses. My research investigates the host cellular response to neurotropic enteroviruses to understand mechanisms of pathogenicity in the central nervous system, which may identify potential therapy targets. These studies expand our knowledge of which enteroviruses are able to infect and replicate in nervous system-derived cell lines and determine viral kinetics for several enteroviruses within those cell lines. By examining host cell responses to enterovirus infection, and confirming the significance of host proteins in knockdown cell lines, this work will elucidate mechanisms that modulate neurovirulence and identify potential targets for future therapeutic research.
Wastewater surveillance and public health (view the poster here)
Wastewater-based epidemiology has been a powerful tool for community-level surveillance of SARS-CoV-2 virus during the COVID-19 pandemic. Individual diagnostic testing is inherently biased due to assumptions of access and voluntary participation. While wastewater surveillance offers a different set of biases, it has revolutionary potential to guide effective resource allocation through low-resolution monitoring at unprecedented scale and low cost. As governments build capacity for these tools, conversations are needed about the many biomarkers of human health, behaviour and identity that can be detected through our sewage systems. While the potential for abuse of this information is low, wastewater epidemiology is inherently distasteful and invasive; it uses data collected from our most private moments to glean insights into other deeply personal information, like our health and consumption habits, and can be correlated with income and cultural identity. The potential exists for misuse of these data, particularly when combined with other personal information or in controlled settings like prisons. Researchers and institutions must be accountable not just for the data they produce, but also how those data are used by law enforcement, government and industry partners.
Re-envisioning informed consent for the genomic era (view the poster here)
Personalized medicine promises a patient’s unique genetic, biochemical, environmental and lifestyle factors can inform preventive rather than reactive care, improve efficacy and quality of life, minimize potential complications and reduce costs. It promises to disentangle the heterogeneity of disease etiology to help understand how a disease can manifest in strikingly different ways between patients. However, in exchange for potential benefits, participants can be asked to offer genetic information with very few commitments in return. In North America, biological materials are assessed under property law and therefore can only have a singular owner. Compared to traditional relationships between participants and researchers, direct-to-consumer genetic testing uses economic models, with clients rather than patients. There are also calls for bidirectional dialogue over samples in research contexts. Current models do not offer clarification on participant rights and, significantly, biological databanks suffer from biological monocultures and participant choice will not improve issues of biodiversity and broad representation. This lack of diversity must be addressed for biobanks to offer meaningful data. While research is inherently risky, those conducting research are often least at risk from data misuse. Benefit-sharing models and community-engaged research are broadly supported but rely on ongoing dialogue in good faith and often cannot be directly translated between different research programs and cultural contexts. The Government of Canada does not appear prepared to use legislative tools to specifically regulate the uses of biological materials. Researchers, academic journals and funding agencies are taking a more active role in encouraging ethical practice, but may be less effective at guiding corporate practices.
Governance of dual-use research in the life sciences
The term dual-use refers to research with legitimate scientific applications, such as the development of vaccines, but could also be used to harm people, the environment or society, such as a terrorist attack. While regulating the practice and distribution of dual-use research is appropriate, framing these policies as a matter of national security can also have a chilling effect on scientific progress, international collaborations and beneficial uses. A significant avenue for dual-use technology proliferation is through legitimate academic journals and conferences. In 2011, the Dutch government required a group of researchers studying avian influenza to receive an export permit to distribute their findings, which was the first instance of a government framing publication as exportation of controlled goods. Since 2016, Australia requires researchers to apply to the Department of Defence prior to sharing dual-use research with international collaborators or academic journals. Canada’s current strategy focuses on education and outreach to academic institutions to minimise dual-use risks throughout the research process, including eventual publication. However, the Canadian government’s legacy of muzzling scientists has led to some researchers being skeptical of policies that could be used to silence them for political reasons. In an era of unprecedented opportunity for global partnerships, securitization threatens to smother legitimate efforts to fight disease. The threat of bioterrorism based on proliferation of new dual-use technologies is negligible compared to the ongoing suffering and death caused by natural infectious diseases. Canada’s policies must not fixate on potential fears of tomorrow at the cost of saving lives today.
Enterovirus infections cause half the clinical cases of aseptic meningitis. Enteroviruses, single-stranded positive-sense RNA viruses of the family Picornaviridae, are associated with illnesses including hand, foot and mouth disease, myocarditis, encephalitis and acute flaccid paralysis. Poliomyelitis is caused by three serotypes of enterovirus, but several non-polio enteroviruses also cause neurological disease. Outbreaks of Enterovirus D68 in 2014, 2016 and 2018 were associated with acute flaccid myelitis and these new strains are able to replicate in human neuroblastoma cell culture. Echovirus 6 has also shown increased neurovirulence since 2016. Due to a lack of understanding of enterovirus pathogenesis, there are currently no effective specific therapies for any non-polio enteroviruses. My research investigates the host cellular response to neurotropic enteroviruses to understand mechanisms of pathogenicity in the central nervous system, which may identify potential therapy targets. These studies expand our knowledge of which enteroviruses are able to infect and replicate in nervous system-derived cell lines and determine viral kinetics for several enteroviruses within those cell lines. By examining host cell responses to enterovirus infection, and confirming the significance of host proteins in knockdown cell lines, this work will elucidate mechanisms that modulate neurovirulence and identify potential targets for future therapeutic research.
Wastewater surveillance and public health (view the poster here)
Wastewater-based epidemiology has been a powerful tool for community-level surveillance of SARS-CoV-2 virus during the COVID-19 pandemic. Individual diagnostic testing is inherently biased due to assumptions of access and voluntary participation. While wastewater surveillance offers a different set of biases, it has revolutionary potential to guide effective resource allocation through low-resolution monitoring at unprecedented scale and low cost. As governments build capacity for these tools, conversations are needed about the many biomarkers of human health, behaviour and identity that can be detected through our sewage systems. While the potential for abuse of this information is low, wastewater epidemiology is inherently distasteful and invasive; it uses data collected from our most private moments to glean insights into other deeply personal information, like our health and consumption habits, and can be correlated with income and cultural identity. The potential exists for misuse of these data, particularly when combined with other personal information or in controlled settings like prisons. Researchers and institutions must be accountable not just for the data they produce, but also how those data are used by law enforcement, government and industry partners.
Re-envisioning informed consent for the genomic era (view the poster here)
Personalized medicine promises a patient’s unique genetic, biochemical, environmental and lifestyle factors can inform preventive rather than reactive care, improve efficacy and quality of life, minimize potential complications and reduce costs. It promises to disentangle the heterogeneity of disease etiology to help understand how a disease can manifest in strikingly different ways between patients. However, in exchange for potential benefits, participants can be asked to offer genetic information with very few commitments in return. In North America, biological materials are assessed under property law and therefore can only have a singular owner. Compared to traditional relationships between participants and researchers, direct-to-consumer genetic testing uses economic models, with clients rather than patients. There are also calls for bidirectional dialogue over samples in research contexts. Current models do not offer clarification on participant rights and, significantly, biological databanks suffer from biological monocultures and participant choice will not improve issues of biodiversity and broad representation. This lack of diversity must be addressed for biobanks to offer meaningful data. While research is inherently risky, those conducting research are often least at risk from data misuse. Benefit-sharing models and community-engaged research are broadly supported but rely on ongoing dialogue in good faith and often cannot be directly translated between different research programs and cultural contexts. The Government of Canada does not appear prepared to use legislative tools to specifically regulate the uses of biological materials. Researchers, academic journals and funding agencies are taking a more active role in encouraging ethical practice, but may be less effective at guiding corporate practices.
Governance of dual-use research in the life sciences
The term dual-use refers to research with legitimate scientific applications, such as the development of vaccines, but could also be used to harm people, the environment or society, such as a terrorist attack. While regulating the practice and distribution of dual-use research is appropriate, framing these policies as a matter of national security can also have a chilling effect on scientific progress, international collaborations and beneficial uses. A significant avenue for dual-use technology proliferation is through legitimate academic journals and conferences. In 2011, the Dutch government required a group of researchers studying avian influenza to receive an export permit to distribute their findings, which was the first instance of a government framing publication as exportation of controlled goods. Since 2016, Australia requires researchers to apply to the Department of Defence prior to sharing dual-use research with international collaborators or academic journals. Canada’s current strategy focuses on education and outreach to academic institutions to minimise dual-use risks throughout the research process, including eventual publication. However, the Canadian government’s legacy of muzzling scientists has led to some researchers being skeptical of policies that could be used to silence them for political reasons. In an era of unprecedented opportunity for global partnerships, securitization threatens to smother legitimate efforts to fight disease. The threat of bioterrorism based on proliferation of new dual-use technologies is negligible compared to the ongoing suffering and death caused by natural infectious diseases. Canada’s policies must not fixate on potential fears of tomorrow at the cost of saving lives today.