George Chaconas obtained his Ph.D. at the University of Calgary in Alberta, Canada in 1978 and completed postdoctoral studies at Cold Spring Harbor Laboratory in New York. In 1981 he returned to Canada to take up a position as an Assistant Professor in the Department of Biochemistry and the Department of Microbiology & Immunology at the University of Western Ontario. His research focused on the mechanism of DNA transposition by the temperate bacteriophage Mu. In the 1999-2000 year Dr. Chaconas spent a sabbatical year at the National Institute of Allergy and Infectious Diseases Rocky Mountain Labs in Hamilton, Montana, USA. This sabbatical was the start of a new research interest on the Lyme disease spirochete. In 2002 he took a position in the Bacterial Pathogenesis Research Group (Department of Biochemistry & Molecular Biology and the Department of Microbiology & Infectious Diseases) at the University of Calgary. He currently holds the Tier 1 Canada Research Chair in the Molecular Biology of Lyme borreliosis and a Scientist Award from the Alberta Heritage Foundation for Medical Research.
“Functional studies of the Lyme disease
spirochete – from mice to molecules” George Chaconas, University
of Calgary
Lyme borreliosis, also
known as Lyme disease, is now the most
common vector transmitted disease in the
northern hemisphere. It is caused by the
spirochete Borrelia burgdorferi and related
species. In addition to their clinical
importance, these organisms are fascinating
to study because of the wide variety of
unusual features they possess. Ongoing work
in the lab in several areas will be
described:
The segmented genomes
contain up to two dozen genetic elements,
the majority of which are linear with
covalently closed hairpin ends. These linear
DNAs also display a very high degree of
ongoing genetic rearrangement. Mechanisms
for these processes will be described.
Persistent infection by Borrelia species
requires antigenic variation through a
complex DNA rearrangement process at the
vlsE locus on the linear plasmid lp28-1.
Novel features of a unique recombination
process will be presented.
Evidence
for a new global regulator of gene
transcription in the form of an RNA helicase
will be described.
The mechanism of
B. burgdorferi to effectively disseminate
throughout its host is being studied in real
time by high-resolution intravital imaging
in live mice. Recent work will be presented.
This lecture is made possible with the financial support of
Canadian Science Publishing. Their commitment and service to microbiological research and teaching in Canada is greatly appreciated.
2011 Cangene Gold Medal Award
Karlene Lynch
Karlene Lynch is a PhD candidate in the Department of Biological Sciences at the University of Alberta. She received a BSc Honours in Immunology and Infection from the U of A in 2006 and has been a member of the laboratory of Dr. Jonathan Dennis since 2004. Karlene’s research focuses on the genome sequences of Burkholderia cepacia complex bacteriophages and the manipulation of these viruses to make them better candidates for clinical use in cystic fibrosis patients. In addition to co-authoring manuscripts, conference presentations, book chapters, and a patent pending, she has received studentship funding from Alberta Innovates Health Solutions, Cystic Fibrosis Canada, the Natural Sciences and Engineering Research Council of Canada, and the Killam Trusts.
“Genomic analysis and modification of
Burkholderia cepacia complex bacteriophages” Karlene Lynch, University
of Alberta
The Burkholderia
cepacia complex (BCC) is a group of
seventeen Gram-negative environmental
species that cause potentially fatal
opportunistic infections in cystic fibrosis
(CF) patients. Although its prevalence in
these individuals is lower than that of
Pseudomonas aeruginosa, the BCC remains
a serious problem in the CF community
because of the pathogenicity,
transmissibility, and inherent antibiotic
resistance of these organisms. An
alternative treatment for BCC infections
that is currently being developed is
bacteriophage (or phage) therapy, the
clinical use of viruses that infect
bacteria. In order to assess the suitability
of individual phage isolates for therapeutic
use, we have determined and analyzed the
complete genome sequences of a panel of
eleven BCC-specific phages. These sequences
range from 32 to 62 kilobases in length and
encode a broad range of proteins with a
gradient of relatedness to other phage and
bacterial gene products. Respirable powders
of two of these phages have been developed
for aerosol administration and the phages
therein were determined to be both active
and stable. Although we established that
none of these eleven phages encode putative
virulence factors, their temperate nature
may be considered a drawback with respect to
their potential for use in a phage therapy
protocol. To circumvent this problem, we
engineered a lytic mutant of a
Burkholderia pyrrocinia prophage by
knocking out its putative repressor gene.
The resulting phage did not form stable
lysogens and was active against a CF
epidemic strain in an invertebrate infection
model, thus providing a proof-of-principle
that temperate phages can be engineered to
become lytic and that these constructs are
active in vivo. Both the genomic
characterization and subsequent engineering
and modification of BCC-specific phages are
fundamental to the development of an
effective phage therapy strategy for the
BCC.
This lecture is made possible with the financial support of Cangene. Their commitment and service to
microbiological research and teaching in Canada is greatly appreciated.
2011 Fisher Scientific Award
Mariela Segura
Mariela Segura, M.Sc., Ph.D., is
a Junior Scientist of the Swine Infectious Disease Research Centre,
and Assistant Professor at the University of Montreal in the
department of Pathology and Microbiology. She received her M.Sc. and
Ph.D. from the Faculty of Medicine of the University of Montreal,
where she studied the interactions of Streptococcus suis, an
important swine and human pathogen, with host cells and the molecular
basis of the inflammatory response induced by this microorganism. She
carried out a first Post-Doctoral training on signalling pathways
involved in phagocytosis resistance by encapsulated pathogens under
the supervision of Dr. Martin Olivier, at the Infectious Disease Unit,
Laval University, Quebec. Motivated by the field of infectious disease
immunology, Dr. Segura joined Dr. Mary Stevenson’s Laboratory at the
international renowned McGill Centre for the Study of Host Resistance
as a Post-Doctoral Fellow to work on an NIH-funded project to
investigate the effect of concurrent helminth infections, which
coexist in malaria-endemic areas, on the development of anti-malarial
immunity and malaria-induced immunopathology, contributing to the
establishment of a helminth and malaria co-infection model. Dr. Segura
was awarded with Post-doctoral Fellowships by both the Fonds de la
recherche en santé du Québec (FRSQ) and the Canadian Institutes of
Health Research (CIHR). During the last year of her post-doctoral
training, she received the UNESCO-L’Oréal Canada for Women in Science
Research Excellence Award. Dr. Segura started her independent research
career at the Faculty of Veterinary Medicine in 2007 after being
granted a FRSQ Carrier Award. For the current phase of her academic
career she combined her expertise on encapsulated Streptoccoccus
with her expertise on immunology to study the mechanisms
underlying the induction of innate and adaptive immunity to
encapsulated Streptococcus and the role of dendritic cells in
orchestrating these responses. Her research aims to dissect the
cellular and molecular basis of immunity to bacterial capsular
polysaccharides (CPS) and develop novel chemical designs to improve
anti-CPS conjugated vaccines.
“Comparative study of two encapsulated
streptococci: The capsular polysaccharide
differently modulates bacterial interactions
with dendritic cells”
Mariela Segura, University of
Montreal
Infections with
encapsulated bacteria cause serious clinical
problems. Besides being poorly immunogenic,
the bacterial capsular polysaccharide (CPS)
cloaks antigenic proteins allowing bacterial
evasion of the host immune system. Despite
the clinical significance of bacterial CPS
and its suggested role in the pathogenesis
of the infection, the mechanisms underlying
innate and, critically, adaptive immune
responses to encapsulated bacteria have not
been fully elucidated. As such, I became
interested in studying the CPS of two
similar, but unique, streptococcal species:
Group B Streptococcus (GBS) and
Streptococcus suis. Both streptococci
are well encapsulated, some capsular types
are more virulent than others, and they can
cause severe meningitis and septicemia. For
both pathogens, the CPS is considered the
major virulence factor. Finally, these two
streptococci are the sole
Gram-positive bacteria possessing
sialic acid in their
capsules. GBS type III is a leading cause of
neonatal invasive infections. S. suis
type 2 is an important swine and emerging
zoonotic pathogen in humans. We recently
characterized the S. suis type 2
CPS. It shares common structural elements
with GBS, but sialic acid is α2,6- rather
than α2,3-linked to Galactose. Differential
sialic acid expression by pathogens might
result in modulation of immune cell
activation. In fact, the composition and
structure of CPS might direct immune
responses more than previously thought and
differentially affects the immuno-pathogenesis
of these bacterial infections. To this aim,
we compared the interactions of these two
sialylated encapsulated bacteria with
dendritic cells (DCs), known as the most
potent antigen-presenting cells linking
innate and adaptive immunity. Using confocal
and electron microscopy combined with
phagocytosis assays, we showed that S. suis
CPS destabilizes lipid microdomains and
prevents LacCer accumulation at the
phagocytic cup during infection, allowing
bacterial evasion of phagocytosis.
Alternatively, GBS CPS selectively engages
lipid raft domains as a mechanism of entry
and intracellular survival. In fact, GBS
uses several endocytosis pathways, including
lipid-raft dependent but caveolin-independent
and clathrin-mediated endocytosis to
modulate its intracellular fitness. The
outcome of both interactions alters cytokine
production patterns differently, which might
affect DC capacity to activate T cells and
consequent orchestration of adaptive immune
responses. Data from these studies will give
new insights into the pathogenesis of
encapsulated bacteria-induced disease and
the role of sialylated CPS in the
interactions between bacteria and host
immune cells. Elucidation of the molecular
and cellular basis of the impact of CPS
composition on bacterial interactions with
immune cells is critical for mechanistic
understanding of anti-CPS responses.
Knowledge generated will help to advance the
development of novel, more effective
anti-CPS vaccines and improved
immunotherapies.
This lecture is made possible with the financial support of Fisher Scientific. Their commitment and service to microbiological research and teaching in Canada is greatly appreciated.
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