Current research projects in the lab include:


Gene transfer agents and genetic exchange in Bacteria

Avian influenza viruses in wild birds

Seabirds and movement of Lyme disease-causing Borrelia

Aleutian disease virus in wild and farmed animals

California serogroup viruses in Newfoundland

Gene transfer agents and genetic exchange in Bacteria


Gene transfer between cells is one of the major contributors to bacterial evolution, and viruses are one of the important mediators of such gene exchange (1). Gene transfer agents (GTAs) (2) are virus-like entities that package small pieces of a cell's genome and transfer this DNA to other cells. The purple non-sulfur alphaproteobacterium Rhodobacter capsulatus produces a GTA (3) called RcGTA, and each RcGTA particle packages approximately 4 kb of cellular DNA that can be transferred to other R. capsulatus cells. It provides an excellent model system to study virus-mediated gene transfer in Bacteria.


We are currently studying the regulation of RcGTA production, which is controlled through the actions of a number of different cellular regulatory systems. These include a histidyl-aspartyl phosphorelay network involving the CtrA, CckA and ChpT proteins (4, 5), quorum sensing involving the GtaI and GtaR proteins (6, 7), and a partner-switching system involving the RbaV and RbaW proteins (8).


There is a cluster of ~15 genes in the R. capsulatus genome that encodes the RcGTA particle structure. In addition to R. capsulatus, this gene cluster is found in many other bacterial genomes. Complete RcGTA-like gene clusters are present in most genomes from within the order Rhodobacterales, and many genome sequences from species of alphaproteobacteria have at least some of these RcGTA-like genes (2, 9, 10). Alphaproteobacteria, and Rhodobacterales in particular (11), are abundant in marine environments. Therefore, if these gene clusters are functional in some of these Bacteria, there could be GTA production and GTA-mediated gene exchange occurring in marine environments. It is well established that viruses are abundant in the sea (12), and it is possible that GTAs represent a fraction of these viral communities. We are using culture-independent approaches to characterize the diversity of RcGTA-like genes in natural microbial communities as well as isolating and characterizing potential GTA-producing strains (13, 14, 15).


Collaborators

Tom Beatty, Department of Microbiology and Immunology, University of British Columbia

Alison Buchan, Department of Microbiology, University of Tennessee

Stephen Callister and Aaron Wright, Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory

Feng Chen, University of Maryland Center for Environmental Science

Martin Mulligan, Department of Biochemistry, Memorial University

Lourdes Peña-Castillo, Departments of Biology and Computer Science, Memorial University

Richard Rivkin, Department of Ocean Sciences, Memorial University

Olga Zhaxybayeva, Department of Biological Sciences, Dartmouth College


References

1. Canchaya, C., G. Fournous, S. Chibani-Chennoufi, M.-L. Dillmann, and H. Brussow. 2003. Phage as agents of lateral gene transfer. Current Opinion in Microbiology 6: 417-424

2. Lang, A.S., O. Zhaxybayeva, and J.T. Beatty. 2012. Gene Transfer Agents: phage-like elements of genetic exchange. Nature Reviews Microbiology 10: 472-482

3. Marrs, B.L. 1974. Genetic recombination in Rhodopseudomonas capsulata. Proceedings of the National Academy of Sciences USA 71: 971-973

4. Lang, A.S., and J.T. Beatty. 2000. Genetic characterization of a novel bacterial genetic exchange element: the gene transfer agent (GTA) of Rhodobacter capsulatus. Proceedings of the National Academy of Sciences USA 97: 859-864

5. Mercer, R.G., M. Quinlan, A.R. Rose, S. Noll, J.T. Beatty, and A.S. Lang. 2012. Regulatory systems controlling motility and gene transfer agent production and release in Rhodobacter capsulatus. FEMS Microbiology Letters 331: 53-62

6. Schaefer, A.L., T.A. Taylor, J.T. Beatty, and E.P. Greenberg. 2002. Long-chain acyl-homoserine lactone quorum-sensing regulation of Rhodobacter capsulatus gene transfer agent production. Journal of Bacteriology 184: 6515-6521

7. Leung, M.M., C.A. Brimacombe, G.B. Spiegelman, and J.T. Beatty. 2012. The GtaR protein negatively regulates transcription of the gtaRI operon and modulates gene transfer agent (RcGTA) expression in Rhodobacter capsulatus. Molecular Microbiology 83: 759-774

8. Mercer, R.G., and A.S. Lang. 2014. Identification of a predicted partner-switching system that affects production of the gene transfer agent RcGTA and stationary phase viability in Rhodobacter capsulatus. BMC Microbiology 14: 71

9. Lang, A.S., and J.T. Beatty. 2007. Importance of widespread Gene Transfer Agent genes in alphaproteobacteria. Trends in Microbiology 15: 54-62

10. Biers, E.J., K. Wang, C. Pennington, R. Belas, F. Chen, and M.A. Moran. 2008. Occurrence and expression of gene transfer agent genes in marine bacterioplankton. Applied and Environmental Microbiology 74: 2933-2939

11. Buchan, A., J.M. Gonzalez, and M.A. Moran. 2005. Overview of the marine Roseobacter lineage. Applied and Environmental Microbiology 71: 5665-5677

12. Suttle, C.A. 2007. Marine viruses - major players in the global ecosystem. Nature Reviews Microbiology 5: 801-812

13. Zhao Y., K. Wang, C. Budinoff, A. Buchan, A. Lang, N. Jiao, and F. Chen. 2009. Gene transfer agent (GTA) genes reveal diverse and dynamic Roseobacter and Rhodobacter populations in the Chesapeake Bay. ISME Journal 3: 364-373

14. Fu, Y., D.M MacLeod, R.B. Rivkin, F. Chen, A. Buchan, and A.S. Lang. 2010. High diversity of Rhodobacterales in the subarctic North Atlantic Ocean and gene transfer agent protein expression in isolated strains. Aquatic Microbial Ecology 59: 283-293

15. Fu, Y., K.F. Keats, R.B. Rivkin, and A.S. Lang. 2013. Water mass and depth determine the distribution and diversity of Rhodobacterales in an Arctic marine system. FEMS Microbiology Ecology 84: 564-576


Current and previous funding

Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory

Gordon and Betty Moore Foundation

Research and Development Corporation, Leverage Program

NSERC

Research in the Lang lab

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Influenza A viruses in wild birds


Influenza A virus (IAV) is one of the most interesting and important viruses on our planet. IAVs have the ability to infect numerous species of birds and mammals and they have significant global impacts on human health and agriculture. The primary natural reservoir of IAV is wild birds and the evolutionary dynamics within these avian influenza A viruses (AIVs) play important roles in the emergence of new strains that have ramifications for multiple aspects of human society (1). Distinct biogeographic lineages of AIV genes exist in birds, generally divided as North American, South American, Eurasian, and possibly Antarctic (2, 3, 4). The Province of Newfoundland and Labrador is the most easterly region of North America and is also partially contained within the North Atlantic Ocean. This results in migratory bird connections with other portions of Atlantic North America, the Arctic, and across the Atlantic Ocean to Europe. These connections make Newfoundland and Labrador an interesting and important location to study the movements of AIVs in wild birds and this region represents a potential entry point for Eurasian influenza viruses, including the highly pathogenic H5N1 virus (5), into North America.


We are studying the prevalence and diversity of AIVs in wild bird populations of Newfoundland and Labrador. Much of our work takes place on Gull Island, located in the Witless Bay Ecological Reserve. This island is home to large breeding populations of seabirds, such as Common Murre and Atlantic Puffin, and Herring Gull. We are also studying AIV in waterfowl (6, 7), and this work is largely focused in the St. John's region where the dominant species is American Black Duck. This research has shown that species of birds that move between this province and Europe, or that share wintering ranges with birds from Europe, carry influenza viruses that contain mixtures of North American and European genes (8, 9). This has helped illuminate the potential role of these marine birds in the movement of IAVs around the globe. It is also important to keep track of the viruses present in wild birds for potential source tracking in the event of transmission to poultry. With our collection of viruses from different bird species we are now working to understand the properties that allow individual AIVs to infect and propagate in some species but not others.


Collaborators

Yohannes Berhanne, Canadian Food Inspection Agency

Davor Ojkic, Animal Health Laboratory, University of Guelph

Andy Ramey, United States Geological Survey, Alaska Science Center

Gregory Robertson, Wildlife Science Directorate, Environment Canada

Hugh Whitney, NL Department of Natural Resources (retired)


References

1. Salomon, R., and R.G. Webster. 2009. The influenza virus enigma. Cell 136: 402-410

2. Olsen, B., V.J. Munster, A. Wallensten, J. Waldenstrom, A.D.M.E. Osterhaus, R.A.M. Fouchier. 2006. Global patterns of influenza A virus in wild birds. Science 312: 384-388

3. Gonzalez-Reiche, A.S., and D.R. Perez. 2012. Where do avian influenza viruses meet in the Americas? Avian Diseases 56: 1025-1033

4. Hurt, A.C., D. Vijaykrishna, J. Butler, C. Baas, S. Maurer-Stroh, M.C. Silva-de-la-Fuente, G. Medina-Vogel, B. Olsen, A. Kelso, I.G. Barr, and D. González-Acuña. 2014. Detection of evolutionarily distinct avian influenza A viruses in Antarctica. mBio 5: e01098-14

5. Watanabe, Y., M.S. Ibrahim, Y. Suzuki, and K. Ikuta. 2012. The changing nature of avian influenza A virus (H5N1). Trends in Microbiology 20: 11-20

6. Huang Y., M. Wille, A. Dobbin, N. Walzthöni, G.J. Robertson, D. Ojkic, H. Whitney, A.S. Lang. 2014. Genetic structure of avian influenza viruses from ducks of the Atlantic flyway of North America. PLoS ONE 9: e86999

7. Huang, Y., M. Wille, A. Dobbin, G.J. Robertson, P. Ryan, D. Ojkic, H. Whitney, and A.S. Lang. 2013. A four-year study of avian influenza virus prevalence and subtype diversity in ducks of Newfoundland, Canada. Canadian Journal of Microbiology 59: 701-708

8. Wille, M., G.J. Robertson, H. Whitney, D. Ojkic, and A.S. Lang. 2011. Reassortment of American and Eurasian genes in an influenza A virus isolated from a Great Black-backed Gull (Larus marinus), a species demonstrated to move between these regions. Archives of Virology 156: 107-115

9. Huang, Y., G.J. Robertson, D. Ojkic, H. Whitney, and A.S. Lang. 2014. Diverse inter-continental and host lineage reassortant avian influenza A viruses in pelagic seabirds. Infection, Genetics and Evolution 22: 103-111


Current and previous funding

Canadian Food Inspection Agency

Environment Canada, Strategic Technology Applications of Genomics in the Environment program

Environment Canada, Wildlife and Landscape Science Directorate

NL Agriculture and Agrifoods Research and Development Program

NL Department of Natural Resources

NSERC


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Seabirds and movement of Lyme disease-causing Borrelia


On mainland North America, the causative agent of Lyme disease is the spirochaete Borrelia burgdorferi, which is transmitted to people from its animal reservoir via infected blacklegged ticks (Ixodes scapularis). In other locations there are different species of Borrelia that cause Lyme disease, and these are transmitted by different species of ticks (1, 2). One of these is B. garinii, which is found in the seabird tick, I. uriae (3). Although they are occasionally found here, there is currently no evidence of an established population of I. scapularis in the province of Newfoundland and Labrador. However, I. uriae are regularly found on seabirds here and some of these ticks have been found to carry B. garinii (4) and B. bavariensis (5).


We are studying the prevalence and genetic diversity of B. garinii in seabirds to understand its transmission and population structure in this province. We are also interested in the relationship between B. garinii diversity and the I. uriae population structure and the different host seabird species.


Collaborators

Robbin Lindsay, National Microbiology Lab, Public Health Agency of Canada

Nicholas Ogden, Zoonoses Division, Centre for Food-borne, Environmental & Zoonotic Infectious Diseases, Public Health Agency of Canada

Gregory Robertson, Wildlife Science Directorate, Environment Canada

Bruce Rodrigues, NL Wildlife Division

Hugh Whitney, NL Department of Natural Resources (retired)


References

1. Radolf, J.D., M.J. Caimano, B. Stevenson, and L.T. Hu. 2012. Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes. Nature Reviews Microbiology 10: 87-99

2. Mannelli, A., L. Bertolotti, L. Gern, and J. Gray. 2012. Ecology of Borrelia burgdorferi sensu lato in Europe: transmission dynamics in multi-host systems, influence of molecular processes and effects of climate change. FEMS Microbiology Reviews 36: 837-861

3. Olsen, B., T.G.T. Jaenson, L. Noppa, J. Bunikis, and S. Bergstrom. 1993. A Lyme borreliosis cycle in seabirds and Ixodes uriae ticks. Nature 362: 340-342

4. Smith, R.P., S.B. Muzaffar, J. Lavers, E.H. Lacombe, B.K. Cahill, C.B. Lubelczyk, A. Kinsler, A.J. Mathers, and P.W. Rand. 2006. Borrelia garinii in seabird ticks (Ixodes uriae), Atlantic Coast, North America. Emerging infectious diseases 12: 1909–1912

5. Munro, H.M., N.H. Ogden, L.R. Lindsay, G.J. Robertson, H. Whitney, and A.S. Lang. 2017. Evidence for Borrelia bavariensis infections of Ixodes uriae within seabird colonies of the North Atlantic Ocean. Applied and Environmental Microbiology (in press)


Current and previous funding

Public Health Agency of Canada, Zoonoses Division

NL Agriculture and Agrifoods Research and Development Program

NL Department of Natural Resources

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Aleutian disease virus and related parvoviruses in wild and farmed animals


Aleutian disease (AD) results from infection by amdoparvovirus, a member of the family Parvoviridae (1, 2). AD is an important disease in mink, related mustelids, and other fur-bearing mammals, and is a significant infectious disease in the commercial mink industry. We are studying the evolutionary relationships of amdoviruses present in wild and farmed animals (3). This will help to determine the source of viruses that currently exist on farms and allow us to look at movements within the wild animal population. We have also discovered a novel related amdovirus in skunks (4) and investigated parvovirus circulation in coyotes (5) and raccoons (6).


Collaborators

Viking Fur Inc.

NuMink Inc

Ann Britton, BC Animal Health Centre

Davor Ojkic, Animal Health Laboratory, University of Guelph

Grant Spearman, NS Department of Agriculture

Hugh Whitney, NL Department of Natural Resources (retired)


References

1. Porter, D.D. 1986. Aleutian disease: a persistent parvovirus infection of mink with a maximal but ineffective host humoral immune response. Progress in Medical Virology 33: 42-60

2. Cotmore, S.F., and P. Tattersall. 2014. Parvoviruses: Small does not mean simple. Annual Review of Virology 1: 517-537

3. Canuti, M., et al. 2016. Driving forces behind the evolution of the Aleutian mink disease parvovirus in the context of intensive farming. Virus Evolution 2: vew004

4. Canuti, M., H.E. Doyle, A. Britton, and A.S. Lang. 2017. Full genetic characterization and epidemiology of a novel amdoparvovirus in striped skunk (Mephitis mephitis). Emerging Microbes and Infections 6: e30

5. Canuti, M., B. Rodrigues, H.G. Whitney, and A.S. Lang. Introduction of canine parvovirus 2 into wildlife on the Island of Newfoundland, Canada. Infection, Genetics and Evolution 55: 205-208

6. Canuti, M., A.P. Britton, S.M. Graham, and A.S. Lang. Epidemiology and molecular characterization of protoparvoviruses infecting wild raccoons (Procyon lotor) in British Columbia, Canada. Virus Research (in press)


Current and previous funding

NL Agriculture and Agrifoods Research and Development Program

NL Department of Natural Resources

NSERC (Engage and CRD Programs)

Joint Mink Research Committee

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California serogroup viruses in Newfoundland


This project aims at investigating the prevalence and distribution patterns of Snowshoe Hare Virus (SSH) and Jamestown Canyon Virus (JCV), both of which are mosquito-transmitted and members of the California Serogroup Viruses in the family Bunyaviridae. These viruses occur in wild animals, but occasionally can be transmitted to humans via mosquitoes (1). We have documented the presence of SSH in mosquitos in Newfoundland and their circulation in wiuldlife (2).


Collaborators

Tom Chapman, Department of Biology

Michael Drebot, National Microbiology Lab, Public Health Agency of Canada

Joel Finnis, Department of Geography

Atanu Sarkar, Memorial University Faculty of Medicine

Hugh Whitney, NL Department of Natural Resources (retired)


References

1. Calisher, C.H. 1994. Medically important arboviruses of the United States and Canada. Clinical Microbiology Reviews 7: 89-116

2. Carson, P.K., K. Holloway, K. Dimitrova, L. Rogers, A.C. Chaulk, A.S. Lang, H.G. Whitney, M.A. Drebot, and T.W. Chapman. 2017. The seasonal timing of Snowshoe Hare Virus transmission on the Island of Newfoundland, Canada. Journal of Medical Entomology 54: 712-718


Funding

NL Department of Natural Resources

Public Health Agency of Canada