Publication: Human-specific mutations and positively-selected sites in MARCO confer functional changes.

First author on the publication, PhD student Kyle Novakowski of Dr. Dawn Bowdish’s lab.
A common element that links ancient fish that dwell in the darkest depths of the oceans to land mammals, Neanderthals, and humans is the necessity to defend against pathogens. Hundreds of millions of years of evolution have shaped how our innate immune cells, such as macrophages, detect and destroy microorganisms.

In a new study led by Dr. Dawn Bowdish (in collaboration with Dr. Brian Golding) and her PhD student Kyle Novakowski, the team identified novel sites within a macrophage receptor, MARCO, that are under positive selection and are human-specific. The team demonstrated the importance of these sites by site-directed mutation and showed a reduction in cellular binding and uptake of pathogens. These findings demonstrate how small genetic changes in humans can influence how we defend ourselves against pathogens.

Read the full publication in Oxford University Press.

Human-specific mutations and positively-selected sites in MARCO confer functional changes. Novakowski KE, Yap NVL, Yin C, Sakamoto K, Heit B, Golding GB, Bowdish DME. Mol Biol Evol. 2017 Nov 20. doi: 10.1093/molbev/msx298.
PMID: 2916561

Bowdish lab joins the circus.

The lab that plays together stays (late nights scienc-ing) together, which is why the Bowdish lab had our annual retreat at Zacada circus school.  Here we got some very sore muscles and discussed our successes and challenges of the past year and what our goals and ambitious are for the following year. Go Team!

Our annual lab retreat for 2017 was at Zacada Circus school where we learned the trapeze, silks and ran up and down this ninja wall!
Top: Kyle, Dhanyi, Melodie, Joseph, Dessi, Grace, Pat, Mohammad
Bottom: Sara, Janine, Helen, Jessica, Dawn, Allison, Christian.

Alumnus update: Former Bowdish lab undergraduate Charles Yin wins prestigious Vanier scholarship for his MD/PhD work!

Charles Yin 2012smCongratulations to former Bowdish lab undergraduate student Charles Yin on his week of accomplishments – publishing his paper on one of his undergraduate projects and winning a prestigious CIHR Vanier Scholarship for his MD/PhD work at UWO.
Congrats Charles!

The Bowdish lab is the strongest lab at McMaster and we have the scholarship winners to prove it!

Who’s got the strongest lab at McMaster? I do! We’ve had a great run of success at the Bowdish lab with fully all of our students receiving prestigious scholarships! And that’s not to mention our other successes such as our summer scholarship winners (Jason Fan – IIDR), our students who got their degree and moved on to great things (Dr. Fan Fei – manager of Mass Spec facility, Dr. Mike Dorrington – PDF at the NIH), and our PDF, Dr. Chris Verschoor who got a faculty position!

Who's got the strongest lab at McMaster? I do! Bowdish lab scholarship winners 2015/2016: Netusha Thevaranjan (CIHR-PhD), Avee Naidoo (CIHR-PhD), Kyle Novakowski (NSERC-PhD), Pat Schenck (CIHR-PhD), Dessi Loukov (CIHR-PhD), Justin Boyle (NSERC-MSC).

Bowdish lab scholarship winners 2015/2016: Netusha Thevaranjan (CIHR-PhD), Avee Naidoo (CIHR-PhD), Kyle Novakowski (NSERC-PhD), Pat Schenck (CIHR-PhD), Dessi Loukov (CIHR-PhD), Justin Boyle (NSERC-MSC).

Publication: Tumor necrosis factor drives increased splenic monopoiesis in old mice

bowdish

PhD student Dessi Loukov in the lab of Dr. Dawn Bowdish, recently published a study showing that splenomegaly in old mice is a result of extramedullary hematopoiesis, and that this increased monopoiesis is driven by age-associated increase in TNF. The study compared changes in the microarchitecture and composition of the spleen in old and young mice and found that in old mice, there was an increase in the size and cellularity of the red pulp (the site of hematopoiesis of myeloid precursors). To study the role of TNF in the development of extramedullary hematopoiesis, they used TNF KO mice and found that these mice did not have increased extramedullary monopoiesis. Furthermore, they demonstrated that increased splenic myelopoiesis was a result of the aging microenvironment. This work suggests that strategies which aim to decrease the inflammatory microenvironment that comes with aging, would be effective in reducing inflammatory diseases propagated by cells of the myeloid lineage. Read More

 

Publication: A naturally occurring transcript variant of MARCO reveals the SRCR domain is critical for function

Macrophages play a critical role in innate immunity by detecting, engulfing and destroying pathogenic bacteria and alerting neighbouring immune cells to join the fight against infection. They have many different receptors on their cell surface that allow them to carry out these important processes. A particular group of receptors called Scavenger Receptors are vital to this response. A recent study published in Immunology and Cell Biology by PhD student Kyle Novakowski from the laboratory of Dr. Dawn Bowdish has uncovered a mechanism by which a specific scavenger receptor contributes to macrophage-specific antibacterial immunity.

Scavenger Receptors are evolutionarily ancient and have evolved to recognize a wide array of pathogens by detecting ligands that are common across many pathogenic organisms. A particularly important Scavenger Receptor is Macrophage Receptor with Collagenous Structure, or MARCO. MARCO has been shown to significantly contribute to the clearance of Streptococcus pneumoniae colonization of the nose and in models of pneumococcal pneumonia. The NSERC-funded study took a unique approach to functionally characterizing how MARCO contributes to innate immunity by studying a naturally-occurring variant of the receptor. The study highlighted the importance of a particular domain of the receptor that is required for macrophages to bind and internalize ligands. The study also showed that the domain is necessary to enhance the pro-inflammatory response to pathogenic Streptococcus pneumoniae and can enhance cellular adhesion; both vital to proper macrophage functions.

To read the article, please click here.