About

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Current research interests:

Ducks are the primary host of influenza virus. They can be infected with all strains of influenza, and most cause them little harm. We are interested in both the host-pathogen interactions that permit re-infection, and understanding how the duck successfully clears the virus. Lessons from ducks may identify new strategies to prime our immune defenses against deadly influenza. 

Research in the lab explores fundamental questions in immunology and virology, genetics and evolution. We use a variety of techniques including molecular biology, cell culture, recombinant viruses, real-time PCR, large scale sequencing, florescent microscopy and protein interaction analysis. Our lab is BSL2 certified. We are members of the Li Ka Shing Institute of Virology with many resources for virology. We have access to microscopy facilities, flow cytometry, molecular biology sequencing service units, and other service units on campus. 

Students in the lab work independently on their projects in a collaborative teaching environment. Examples of projects recently completed and in progress are detailed below. Students with relevant background and interest in a project related to these areas of research are encouraged to apply.

Research

 Recent and on-going projects.

1. Avian RIG-I, the sensor for RNA viral infection. 

Ducks, but not chickens, have a functional influenza sensor RIG-I that contributes to the innate immune response to influenza. We showed by bioinformatics and Southern blotting that chickens do not have the RIG-I gene. We can reconstitute chicken cells using duck RIG-I, which is functional in chicken embryonic fibroblast DF-1 cells (a spontaneously immortalized chicken cell line) and confers detection of RIG-I ligand (Barber et al., 2010). This provides a simple explanation for why ducks are resistant to strains of flu that would kill chickens in a few days. Yanna Xiao (PhD) also examined regulation of the RIG-I gene (Xiao et al., 2019). One application of this knowledge is to potentially make cell lines and chickens expressing duck RIG-I for influenza resistance (Eric Friesen, MSc and Adam Moghrabi, MSc Candidate).

Our goal is to understand how RIG-I is regulated in an influenza infection in ducks. We examined RIG-I regulation by ubquitination, and showed that attached ubiquitin is not needed for activation of duck RIG-I (Domingo Miranzo Navarro, PDF PLOS One, 2014). We also showed, in collaboration with Sun Hur, that initiation of MAVS signaling involves oligomerization in a helical structure catalyzed by four RIG-I CARD domains (Wu et al., 2014 Molecular Cell). In this structure RIG-I and MAVS are stabilized by ubiquitin chains. We will follow this up to examine other E3-ubiquitin ligases in activation of RIG-I in ducks (Mirzabek Kazbekov, MSc Candidate)

2. Influenza host-pathogen interactions in ducks

We know influenza can interfere in the innate signaling pathway in many ways, but do not know whether the same is true in ducks, the reservoir host. 

Danyel Evseev, PhD recently examined host-pathogen interactions involving NS1 protein (Evseev et al., 2022 J. Virol.). NS1 impairs TRIM25 ubiquitination required for innate signaling in humans, but not ducks. We also examined the influenza protein PB1-F2 (Yanna Xiao PhD and Adam Moghrabi, MSc candidate) (Xiao et al. 2020 Viruses). PB1-F2 protein does impair innate immune signaling in ducks. Finally, we have also explored PB2 protein inhibition of MAVS signalling (David Tetrault, MSc).  The ways that flu shuts down the host response through these host-pathogen interactions continues to be an active area of study in my lab.

3. Identifying genes involved in antiviral defenses against highly pathogenic avian influenza. 

In collaboration with Robert Webster at St. Jude Children’s Hospital, I carried out experiments in BL3 and obtained tissues from ducks that successfully cleared highly pathogenic avian influenza viruses. Using differential subtractive screening we identified genes upregulated in antiviral responses, and characterized them by real-time PCR (Hillary Vanderven, MSc) (Vanderven et al., 2012 Mol Immunol)(Fleming-Canepa et al., 2018 Veterinary Immunol). Most recently, Lee Campbell, PhD Candidate undertook a full transcriptome sequencing project to identify global changes in gene expression following highly pathogenic and low pathogenic avian influenza infection (Campbell et al., 2021 Front. Immunol.). These studies highlight the importance of innate immune signaling in the response of ducks to influenza, and identify genes potentially involved in influenza defense. 

Candidate antiviral genes will be tested for function. We have focused on interesting gene families including TRIM genes (Alysson Blaine, MSc., Blaine et al., 2014 Mol. Immunol. and Lee Campbell, PhD candidate). Lee is analyzing the duck TRIM repertoire to identify TRIM genes with antiviral activity. Graham Blyth (MSc) also examined the genes encoding IFITM proteins, a small antiviral protein that prevents viral entry (Blyth et al., 2015 J. Virol). There are several other proteins of interest.

4. MHC class I gene organization and diversity in ducks

We showed that the organization of the MHC class I region in ducks has functional implications for severe limitation of the nature of the antigens that can be transported and presented in ducks. Only one MHC class I gene is highly expressed, while 4 others are not (Mesa et al., 2004; Moon et al., 2005). The gene promoters were very similar which was puzzling until Luke Chan (MSc) identified a key non-coding RNA that is involved in their regulation (Chan et al., J. Immunol 2016). We also examined the genetic diversity of MHC class I genes in wild mallards (Shawna Jensen MSc ) and Fleming-Canepa et al., J. Immunol 2016) and TAP transporter genes (Kristina Petkau, MSc). This project is continuing with Deb Moon and Adam Moghrabi recently collecting blood samples from wild ducks to examine more individuals. Some allelic variants of these genes may be better at defense against influenza.

5. Microbiome of Canadian ticks. 

Recent PhD graduate Janet Haley Sperling is using high throughput sequencing technology to survey microbes carried by Canadian ticks (Sperling et al., 2020 Trop. Med Infect. Dis.) (Sperling et al., 2017 Ticks Tick Borne Dis.). Through this work we hope to determine the incidence of bacterial and viral infections carried by ticks. 

IMIN 200 - Infection and Immunity

Introduces the principles and mechanisms of immunity in eukaryotes. Provides an overview of the major groups of infectious agents (virus, bacteria, parasites) and examines selected microorganisms within the context of the host response to pathogens and pathogen evasion strategies. Pre- or corequisites: BIOCH 200 and MICRB 265. May not be taken for credit if credit already obtained in BIOCH 450. (Offered jointly by the Departments of Biological Sciences and Medical Microbiology and Immunology). [Biological Sciences].

IMIN 372 - Research Techniques in Immunology

A lecture and laboratory course covering theory and practice behind selected immunological techniques. Techniques covered may include: lymphocyte isolation, flow cytometry, mixed lymphocyte reactions, immunocytochemistry, immunoprecipitation, ELISA, western blotting, expression cloning and monoclonal antibody technology. Labs will sometimes require students to return the next day to check on plates or cultures. Prerequisite: IMIN 371. May not be taken for credit if credit already obtained in INT D 372. (Offered jointly by the Departments of Biological Sciences and Medical Microbiology and Immunology). [Biological Sciences]

IMIN 401 - Comparative Immunology

The phylogeny and evolution of immune systems. Examines the various strategies for disease resistance used by all organisms from plants to humans. The use and evolution of specific components of innate and adaptive immunity will be considered within the context of the biology of the organisms. This course involves both lectures and graded discussions. Prerequisites: IMIN 371. Credit cannot be obtained for both IMIN 401 and IMIN 501. (Offered jointly by the Departments of Biological Sciences and Medical Microbiology and Immunology). [Biological Sciences].

IMIN 501 - Advanced Comparative Immunology

The phylogeny and evolution of immune systems. Examines the various strategies for disease resistance used by all organisms from plants to humans. The use and evolution of specific components of innate and adaptive immunity will be considered within the context of the biology of the organisms. Lectures and graded discussions are the same as for IMIN 401, but with additional assignments and evaluation appropriate to graduate studies. Prerequisite: Consent of instructor. Credit cannot be obtained for both IMIN 401 and IMIN 501. (Offered jointly by the Departments of Biological Sciences and Medical Microbiology and Immunology). [Biological Sciences].

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