Category Archives: News

Dr. Dawn Bowdish receives a research award from the Ontario Lung Association and Pfizer Canada (and gets to attend a swanky event to receive it!)

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Dawn was thrilled to attend the annual Breathe! gala event hosted as a fundraising event for the Ontario Lung Association to receive an award donated by Pfizer Canada and administered by the Ontario Lung association. Not only did it give her a chance to dress up and go out (a rare event!) for an evening of good food and drink but she was inspired to meet some of the spokespeople of the event, including Helene Campbell, who spent her time waiting for a double lung transplant starting an immensely successful social media campaign to increase organ donation, Ann Marie Cerato, a lung cancer survivor and Kayla Baker, a young sarcoidosis patient on a waiting list for a lung transplant. Not only was it inspiring to meet these brave, bold heroes but it was humbling to be in a room full of people whose lives were all touched by the research funded by the Ontario Lung Association.

Dawn standing beside the real heros of the event, Helene Campbell, double lung transplant recipient and idiopathic fibrosis patient, Ann Marie Cerato, lung cancer survivor and Kayla Baker sarcoidosis patient waiting for a lung transplant.

So what did Dawn win her award for? You can take a look at the YouTube video here or read on…

President of Pfizer Canada, John Helou (L) and Dr. John Granton, chair elect of the Ontario Lung Association (R) present Dr. Dawn Bowdish with the OLA-Pfizer Research Award.

Description of research funded by the Ontario Lung Association-Pfizer Ca award

neumonia is the sixth most common cause of death in Canada.  The incidence of pneumonia rises steeply in individuals over the age of 65 years and approximately 90% of deaths due to pneumonia occur in the elderly (>65 yrs).  Current prevention strategies are inadequate as the vaccination does not prevent pneumonia in most elderly individuals. Recent research from the Bowdish lab demonstrates that one of the reasons the elderly are so susceptible to pneumonia is that their immune systems cannot control the bacteria that normally live in our sinuses. The immune systems of healthy adults can keep the bacteria (Streptococcus pneumoniae) in the sinuses (“pneumococcal carriage”) and eventually clear them, but for reasons we don’t understand, the immune systems of the elderly cannot and as a result the bacteria break through the immune barriers of the sinuses and spread to the lungs, which results in pneumonia.

Although most people think that the elderly get sick because their immune systems “just don’t work”, in fact our data demonstrate that they recruit more white blood cells to the sinuses when they encounter the bacteria that cause pneumonia than healthy adults. Even though they have more white blood cells in the sinuses they don’t seem to be as good at recognizing and killing bacteria. Our goal is to figure out why they have overactive recruitment of white blood cells and why they aren’t as good at killing bacteria as white blood cells from healthy adults.

We have developed what we believe to be the world’s only Aged mouse model of colonization by pneumonia causing bacteria. This allows us to study how the immune system responds to the presence of bacteria in the sinuses in real-time. In addition we have a bank of white blood cells from adults and elderly patients that allow us to confirm the importance of our mouse studies in people.

Hospitalizations and deaths due to pneumonia are unacceptably high in the elderly. This is likely because vaccination of the elderly only does not protect against pneumonia. New methods for preventing infection are urgently required. Our recent data demonstrates that containment and clearance of pneumococcal carriage is impaired in age and results in increased susceptibility to pneumonia; however the mechanisms by which immune control of the sinuses fails remain to be discovered. Prevention of colonization of the sinuses will therefore be essential for control of pneumonia in this population. In order to develop novel therapeutic interventions for the elderly it will be necessary to discover the mechanisms by which bacterial recognition, killing are impaired in the sinuses.

Helene Campbell, conceivably, the most charming woman alive and the recipient of a double lung transplant, leads a dance with the Hon Deborah Mathews (MPP). The music failed so I held my iPod up to the Mike and we played Metric's "Sympathy".

The Bowdish lab is now accepting applications for undergraduate summer/thesis students.

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It may seem early, but the Bowdish lab is now looking for undergraduate students for summer 2013 and the 2013/2014 school year. Generally the model in our lab is to have a student apply for a summer studentship and work full time then continue on as a thesis student. See the FAQ page for requirments http://www.bowdish.ca/lab/faq/.

Previously we have had students in any of the Health Sciences, Biochemistry or Biology thesis programs and are open to accepting students from other programs. We will likely be taking 2, possibly 3 students. The project will be determined based on the successful student’s interests and aptitudes but Dr. Bowdish is especially interested in meeting with students with interest or experience in;

  • Statistics, Biostatistics, Bioinformatics or Computer Science, especially large data set analysis
  • Molecular & Cellular Biology, especially cloning and protein expression
  • Biochemistry, such as protein-protein interactions
  • Chemistry, specifically metabalomics and mass spec
  • Membrane Physics

and of course,

  • Immunology, especially animal models of infection.

Students will be expected to apply for external summer funding (e.g. NSERC-USRA, departmental summer studentships and other). For all other questions on qualifications see the FAQ page http://www.bowdish.ca/lab/faq.

Interested candidates should read the FAQ page and provide Dr. Bowdish with a c.v. and brief reason for why you would like to be part of the Bowdish lab.

 

Mike Dorrington (PhD candidate) discovers that MARCO is required for recognition and removal of S. pneumoniae in the sinuses.

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Despite having multiple vaccines against Streptococcus pneumoniae available today, over a million people die each year due to pneumococcal infections. Mike Dorrington, a Ph.D. candidate in the Bowdish lab, is attempting to understand how to produce better vaccines by gaining a better grasp on how the immune system fights these bacteria. Mike has recently published a manuscript entitled “MARCO is required for TLR2- and NOD2-mediated responses to Streptococcus pneumoniae and clearance of pneumococcal colonization in the murine nasopharynx” in the Journal of Immunology. Mike’s work focuses on the importance of macrophage scavenger receptors in immune protection against S. pneumoniae, the most common cause of bacterial pneumonia. This manuscript provides us with evidence that Macrophage Receptor with Collagenous structure (MARCO), a class A scavenger receptor, plays an integral role in establishing and maintaining the appropriate innate immune response to the bacteria in its preferred niche, the nasal passage.

At the celebration of Mike’s first first author publication. Although Dawn is mostly happy for Mike, she is also slightly nervous that she might be about to lose an eye when the champagne is opened.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

     S. pneumoniae is a very common pathogen that causes fatal disease in children under the age of 5 (where it often causes meningitis) and adults over the age of 65 (where it most often presents in pneumonia). Before infectious disease occurs, bacteria colonize the nasal passages of individuals where they replicate. If the bacteria are able to persist for long enough, they will then move to the lungs, blood, or meninges and cause potentially life-threatening disease. It has previously been shown that the clearance of the bacteria from the nasal passages was dependent on an influx of macrophages to the site. These cells are able to internalize and kill the bacteria efficiently. MARCO is expressed by these active macrophages and has been shown to play a role in the recognition of the bacteria.

Mike’s work shows that mice who lack MARCO expression are unable to clear bacterial colonization in a timely fashion. This is due to a decrease in a number of innate immune functions. First, MARCO-deficient mice have significantly less recruitment of innate immune cells such as neutrophils and macrophages to the site of colonization. Without these cells, the bacteria are free to thrive and replicate in the nasal passage, increasing the chance that they will travel to further tissues and cause disease. MARCO-deficient mice also present with less inflammation than they’re wild-type counterparts, as seen by a paucity of pro-inflammatory cytokines and chemokines including, surprisingly, type I interferons (cytokines associated with antiviral immunity). These data are supported by experiments performed in vitro using macrophage populations from MARCO-deficient and wild-type mice. When these cells are stimulated with S. pneumoniae, the MARCO-deficient macrophages produce less cytokines and chemokines. These cells are also less able to internalize the bacteria, a key step in the destruction of the pathogens.

A potentially ground-breaking finding that comes from Mike’s work is that MARCO is able to modulate the activity of other important innate immune receptors. Mike has shown that NF-kB activation in S. pneumoniae-stimulated cells expressing MARCO along with TLR2 and its co-receptor CD14 is much higher than cells not expressing MARCO. This is also true of cells expressing MARCO as well as NOD2 when compared to those expressing just NOD2. As NF-kB is a central regulator of immune function, this represents a very important step in our understanding of antibacterial innate immune responses in the nose.

Mike’s work on MARCO will continue as he attempts to uncover the mechanism by which MARCO increases NF-kB activation by these other receptors. It is his hope to be able to apply these advances in the basic science to vaccine development in order to generate an effective strain-independent vaccine against S. pneumoniae infection.

Extra, Extra, Read all about it! The Bowdish lab elucidates the evolution of the class A scavenger receptors.

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Congratulations to Fiona Whelan (MSc) for publishing her first manuscript “The Evolution of the class A scavenger receptors” in BMC Evolutionary Biology. The scavenger receptors are an evolutionarily ancient family of proteins required for host defence and homeostasis but teasing apart their function and even their structure has been challenging. The goal of this manuscript was to use evolution as a guide to discover how the class A scavenger receptor family was formed and to identify regions of conservation and hence probable functional importance for future study. Phagocytic receptors such as the class A scavenger receptors are integral members of the innate immune response, which is conserved in all classes of life and after reproduction and nutrient acquisition is probably the major most fundamental requirement for survival.

There are essentially only four basic mechanisms of the innate immune system – agglutination (e.g. lectins), lysis/neutralization (e.g complement, antimicrobial peptides), phagocytosis (e.g. scavenger receptors), and pro-inflammatory signalling (e.g. the toll like receptors). The fact that these processes are ancient and have been so strongly preserved is a testament to their importance. Of these, phagocytosis is likely the most ancient process and was probably adapted from its original purpose of nutrient ingestion . One might hypothesize that phagocytosis was truly the genesis of the immune system since our single celled ancestors had to distinguish  between “self” and “non-self” in order to distinguish between food and their own daughter cells.  From there phagocytosis became essential to fundamental processes such as embryonic development, pathogen recognition, and homeostatic clearance of senescent cells. Without phagocytosis, the transition to more complicated life forms could not have occurred.

Although there have been excellent evolutionary analyses of the lectins, toll like receptors and complement pathways, very little is known about the evolution of the phagocytic receptors. The class A scavenger receptors are an excellent example of these multifunctional receptors as they are involved in both host defence and homestasis. Since the phagocytic receptors in general and the scavenger receptors in particular are a diverse group of proteins,it has been challenging to understand how members within a group are related. Indeed, the first goal of this manuscript was to definitively demonstrate that the members of the class A scavenger receptors, which had been grouped together based on a ragtag combination of ligand binding and some degree of amino acid similarity, were actually a family at all.  Since we were able to trace a probable path of gene duplication and consequent functionalization, we are confident that the 5 members (SRAI/II, MARCO, SCARA3/4/5) are actually related.  Interestingly the class A scavenger receptors may have acquired their long stalk like form with a single scavenger receptor cysteine rich domain (SRCR) around the time of the evolution of fish since, although SRCR domain can be found in invertebrates and single celled organisms, we could not find anything that resembled a modern class A scavenger receptor in any genomes of evolutionarily more ancient organisms such as jellyfish, lampreys and insects.

Because elucidating the function of the specific domains of the scavenger receptors has been so challenging (even the function of the SRCR domain is unclear), ultimately we want to use evolution as a guide to which domains are functionally important (i.e. conserved). In this regard we found that there is a common conserved region in the collagenous domain, which in the type member SRAI, is believed to be the ligand binding domain. In addition conserved domains were identified in the cytoplasmic tail and the coiled-coiled domain. Future experiments will be performed to determine if these domains are necessary for structure, expression, cellular localization or phagocytic function.

The best part of our paper is that it is Open Access so you can enjoy reading it in provisional form today at http://www.biomedcentral.com/1471-2148/12/227/abstract. If you have questions, comments or thoughts, please feel free to contact Dr. Dawn Bowdish at bowdish@mcmaster.ca or on her Google+ account. Dr. Bowdish is always interested in talking with undergraduate or graduate students interested in pursuing studies that use bioinformatics to answer questions about the scavenger receptors, phagocytosis, and structure/function relationships.

A summary of the common motifs in the class A scavenger receptor protein sequences. Conserved motifs present in the protein sequences of these receptors are indicated with coloured boxes at their approximate position within the protein with shout out boxes used to show the level of conservation across the aligned Homo sapiens sequences. From Whelan et al. BMC Evol Biol. BMC Evolutionary Biology 2012, 12:227

Bowdish lab cleans up at the IIDR trainee Day!

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Congratulations to Keith Lee for winning the IIDR Award of Excellence for best undergraduate poster and Julie Kaiser for winning the best graduate poster. Alicja Puchta gave an excellent talk and Mike Dorrington, Preethi Jayanth, Kyle Novakowski, Charles Yin, and the BASEF/IIDR summer internship award winner, Jason Fan all presented excellent posters. Way to go team!

Keith Lee, a 4th year BHSc student, wins the IIDR Award for Excellence for "Best Undergraduate Poster".

 

A blurry Julie Kaiser, presents her work on elucidating host-pathogen interactions of the SMG family.

Jason Fan, a grade 11/12 high school student, and BASEF/IIDR summer internship winner presents an excellent poster on isolating pneumococcal cell wall components.

 

Alicja Puchta makes Dr. Brian Coombes repeat the question after her (very professional, very well received) talk.

 

Dr. Preethi Jayanth presents her work on understanding why the elderly are susceptible to post-influenza pneumonia.

Photo credits to Chantall VanRaay.

Dawn speaks on “Undergraduate Research Opportunities” for the McMaster Undergraduate Research S

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Dawn was delighted to be invited to speak at an information night organized by the McMaster Undergraduate Research in Science Association (MURSA). She presented her perspectives on what she might be looking for in an undergraduate student, why PIs/Professors take on undergraduates and once an undergraduate gets a position, what they need to do to be successful. For her presentation, click here. To learn more about the MURSA see their webpage or Facebook page

Dawn presents her perspectives on why a PI might take an undergraduate researcher and what an undergraduate might do to obtain a research position and be successful in research.

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Congratulations to Zhongyuan Tu on successfully defending his MSc thesis!

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Zhongyuan Tu successfully defended his MSc thesis entitled “Characterization of MARCO mediated endocytosis”, making him the Bowdish lab’s second graduate student to graduate. Longtime followers of bowdish.ca will know that Zhongyuan was the very first student to join the Bowdish lab as an undergraduate thesis and then MSc student. Zhongyuan’s thesis involved tackling how the phagocytic receptor MARCO sends signals through the cell.  Zhongyuan will work until January in the Bowdish lab to finish up important parts of his project and he is currently looking at labs in the U.K. or possibly Canada to do a PhD. Congratulations and good luck Zhongyuan!