Dr. Andrew Lang
Department of Biology
232 Elizabeth Ave.
St. John’s, NL A1B 3X9
709-864-8761 lab phone
Science Building SN3021 (office); SN3006 and SN3025 (labs)
Ph.D., Department of Microbiology and Immunology, University of British Columbia 2000
B.Sc. Honours, Biochemistry, Brock University 1994
I am happy to hear from prospective students that are interested in pursuing graduate studies related to the research projects described below.
Part 1. Virus-mediated gene transfer between bacteria.
Gene transfer between cells is one of the major contributors to bacterial evolution, and viruses are one of the important mediators of gene exchange between cells. The purple non-sulfur alphaproteobacterium Rhodobacter capsulatus produces a bacteriophage-like particle called a gene transfer agent (RcGTA). Each RcGTA particle contains approximately 4-kb of cellular DNA that can be transferred to other R. capsulatus cells. RcGTA is one of several phage-like dedicated gene transfer systems known from a diverse collection of prokaryotes. It provides an excellent model system to study virus-mediated gene transfer because genetic tools are readily available to work with RcGTA and R. capsulatus.
Some of our current research projects with RcGTA and R. capsulatus are:
1. Regulation of transcription of the RcGTA genes and production of RcGTA particles.
Elucidating the mechanisms by which RcGTA production is regulated is an important part of understanding this system. Several features of GTA regulation have been partially described, and it seems there is a complex regulatory network involved. Two genes, ctrA and cckA, that encode cellular phosphorelay signal transduction proteins are involved, and acyl-homoserine lactone quorum sensing also affects RcGTA production. Resolving how the various regulatory pieces come together to produce RcGTA at the appropriate time is important as we try to understand the role RcGTA plays in the natural environment.
The RcGTA gene cluster in the R. capsulatus genome.
We have designed Affymetrix gene expression microarrays based on the R. capsulatus genome sequence. These microarrays are being used to identify members of the ctrA, cckA and quorum sensing regulons, and to investigate the triggers for production of RcGTA. This work is also important for understanding the regulation of motility in R. capsulatus, because flagellar gene expression is also dependent on ctrA. This work is being done in collaboration with Dr. Tom Beatty in the Department of Microbiology and Immunology at UBC.
Studying the regulation of gne expression in R. capsulatus by microarrays is being been partnered with concurrent studies of the R. capsulatus proteome. This work is in collaboration with Drs. Stephen Callister and Aaron Wright in the Biological and Environmental Research program at Pacific Northwest National Laboratory (PNL), and is made possible with funding through the Environmental Molecular Sciences Laboratory at PNL and through the Leverage Program at the Research and Development Corporation.
The first of this work was published in 2010 in Journal of Bacteriology.
2. RcGTA evolution through comparative genomics.
How did RcGTA evolve to its current form in R. capsulatus? Do other species related to R. capsulatus make GTAs? Clusters of genes homologous to those that encode the RcGTA particle are present in many other species. In fact, most species of alphaproteobacteria for which a genome sequence has been determined have some or all RcGTA-like genes. In particular, it seems that complete GTA gene clusters are present in ~all genomes of bacteria within the order Rhodobacterales. This order includes the Roseobacter group that are an abundant and important group of bacteria in marine environments. Complete genome sequence information for bacteria in the Roseobacter group are available at the Roseobase website.
There have been several independent analyses of the GTA clusters found in alphaproteobacteria: in Trends in Microbiology by myself and Tom Beatty, Applied and Environmental Microbiology by Biers et al., and ISME Journal by John Paul.
The GTA genes are also an active part of the global phage gene pool as there is clear evidence that RcGTA-related genes are found in genuine phage genomes. A good example of this is phage RDJLphi1, infecting Roseobacter denitrificans. As more and more complete genome sequences become available, it is possible to more accurately address the question of the origin of RcGTA.
3. Prevalence and diversity of RcGTA-like gene transfer systems in natural environments.
There are large numbers of viral particles present in every environment that has been examined: as many as 100 million per milliliter in aquatic systems and 100 million per gram of soil in terrestrial systems. It is unknown how many of these virus particles might be actively involved in mediating genetic exchange. Alphaproteobacteria are numerous in many natural microbial communities, and given the high prevalence of RcGTA-like gene clusters in the sequenced representatives of this group, RcGTA-like entities could be abundant in natural environments. We are using culture-independent approaches to characterize the diversity of RcGTA-like genes in natural microbial communities. We are also isolating and characterizing potential GTA-producing strains. This currently involves work in Newfoundland waters such as Logy Bay, near St. John’s, and also several Arctic locations. This work is being done in collaboration with Dr. Richard Rivkin at the Ocean Sciences Centre, Dr. Feng Chen at the University of Maryland Center for Environmental Science and Dr. Alison Buchan at University of Tennessee.
Part 2. Avian influenza viruses in Atlantic Canada.
This project started in the fall of 2008, and is a collaboration with Dr. Hugh Whitney, Chief Veterinary Officer (Animal Health Division, NL Department of Natural Resources), Dr. Gregory Robertson of Environment Canada, and Dr. Davor Ojkic at the University of Guelph Animal Health Laboratory. We are characterizing the prevalence and diversity of avian influenza viruses (AIVs) that are present in the wild bird populations of Newfoundland and Labrador. We are also working to determine if there is a link between the particular virus strains (or subtypes) that we identify in the bird population and what viruses are present in environmental or abiotic reservoirs.
Atlantic Puffins at Gull Island, NL
Much of our work takes place on Gull Island, located in the Witless Bay Ecological Reserve. This island contains large numbers of breeding seabirds and gulls, and we are working with a number of these. We are also sampling other species at other locations around the province as possible.
Northern Gannets at Cape St. Mary's, NL
Catching ducks in St. John's, NL
We characterized the first complete genome sequence of an AIV isolated from a Thick-billed Murre, an abundant seabird in Newfoundland and Labrador. We also documented inter-continental reassortment in an AIV from a Great Black-backed Gull, a species that moves between Eastern Newfoundland and Europe.
Additionally, we have been collaborating with Dr. Jonathan Runstadler at the University of Alaska Fairbanks. The Runstadler lab hosted Michelle Wille for 3 months as part of a Michael Smith Foreign Study Supplement Award from NSERC. The results of that research were published in PLoS ONE. Dr. Runstadler has now moved to Massachusetts Intsitute of Technology.
This avian influenza work has been funded by the STAGE program at Environment Canada, the NL Agriculture and Agrifoods Research and Development Program.
Part 3. California Serogroup Viruses in Newfoundland.
This work is also done in collaboration with Dr. Hugh Whitney, along with Dr. Michael Drebot from the National Microbiology Lab in Winnipeg, Dr. Greg Goff from MUN's Grenfell Campus, and Dr. Tom Chapman in Biology at MUN. We are 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 occaisonally can be transmitted to humans via mosquitoes.
Most of the research in my lab is currently supported by a Discovery Grant from NSERC. My lab was established with the assistance of infrastructure support from the Leaders Opportunity Fund from the Canada Foundation for Innovation and the Industrial Research and Innovation Fund from the Government of Newfoundland and Labrador.
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