Macrophage scavenger receptors in host defence

Graduate students and post-doctoral fellows who are eligible for NSERC scholarships/fellowships or who have independent funding will be considered for this position. 

Project Description

The two major class A scavenger receptors are called SRA (scavenger receptor, class A) and MARCO (macrophage receptor with collagenous structure), which have high levels of homology but sharply opposing patterns of regulation. SRA is constitutively expressed on macrophages whereas MARCO expression is inducible and is upregulated in response to toll like receptor agonists. The primary role of SRA appears to be clearance of modified host proteins and lipids while MARCO is associated with the response to infectious disease; however,mice defective in expression of either MARCO or SRA are immunocompromised in multiple models of infection.These receptors are especially important in host defence towards the pulmonary pathogens Streptococcus pneumoniae and Mycobacterium tuberculosis.

We have a number of projects ongoing in the lab;

  1. Studying the evolution of this receptor family to understand the genesis of phagocytosis and the phagocytic receptors.
  2. Studying genetic variation within the class A scavenger receptors and how this alters their function and ultimately disease susceptibility.
  3. Uncovering novel signalling motifs that are required for phagocytosis, motility and pro-inflammatory signalling.
  4. Discovering how these receptors recognize resident pathogens in the upper respiratory tract such as S. pneumoniae and drive an inflammatory response.

Team Members:

Graduate students: Mike Dorrington (PhD candidate), Kyle Novakowski (PhD candidate), Nick Yap (co-supervised with Dr. Brian Golding).

Undergraduate students: Mohammad Malik

Collaborators:

  • Dr Brian Golding & Nick Yap (studies on evolution and genetic variation)
  • Dr. Andrew Wong and Annie Lee (prediction of novel signalling motifs)
  • Dr. Alba Guarne & Angela Huynh (structure/function of SRCR domain)
  • Drs. Kaori Sakamoto & Gary Coulsen (genetic variation and disease susceptibility)

Current Funding: NSERC, NIH, IIDR

Alumni: Fiona Whelan (MSc Sept 2010-2012), Zhongyuan Tu (MSc Sept 2010-2012), Undergraduates: Sarah Chauvin, Alex Jiang, Harikesh Wong, Prashant Bharadwa, James Han, Charles Yin, Nick Yap.

Publications (lab members marked in bold):

  1. Love RJ, Patenaude M, Dorrington M, Bowdish DM, Hoare T, Jones KS. An investigation of scavenger receptor A mediated leukocyte binding to polyanionic and uncharged polymer hydrogels.J  Biomed Mater Res A. 2015 May;103(5):1605-12. doi: 10.1002/jbm.a.35297.
  2. Nellimarla S, Baid K, Loo YM, Gale M Jr, Bowdish DM, Mossman KL. Class A Scavenger Receptor-Mediated Double-Stranded RNA Internalization Is Independent of Innate Antiviral Signaling and Does Not Require Phosphatidylinositol 3-Kinase Activity. J Immunol. 2015 Oct 15;195(8):3858-65. doi: 10.4049/jimmunol.1501028.
  3. Yap N, Whelan FJ, Bowdish DM and Golding B (2015). The Evolution of the Scavenger Receptor Cysteine-Rich Domain of the Class A Scavenger Receptors. Front. Immunol. 6:342. doi: 10.3389/fimmu.2015.00342
  4. Love RJ, Patenaude M, Dorrington M, Bowdish DM, Hoare T, Jones KS. An investigation of scavenger receptor A mediated leukocyte binding to polyanionic and uncharged polymer hydrogels. J Biomed Mater Res A. 2015 May;103(5):1605-12. doi: 10.1002/jbm.a.35297.
  5. PrabhuDas M, Bowdish D, Drickamer K, Febbraio M, Herz J, Kobzik L, Krieger M, Loike J, Means TK, Moestrup SK, Post S, Sawamura T, Silverstein S, Wang XY, El Khoury J. Standardizing scavenger receptor nomenclature. J Immunol. 2014 Mar 1;192(5):1997-2006. doi: 10.4049/jimmunol.1490003.
  6. Bowdish DME., Sakamoto, K., Lack, N.A., Sirugo, G., Newport, M., Gordon, S.,  Hill, AVS., Vannberg, FO., Genetic variants in MARCO are associated with susceptibility to tuberculosis.  BMC Med Genet. 2013 Apr 23;14:47. doi: 10.1186/1471-2350-14-47.
  7. Dorrington, MG., Roche, A., Chauvin, SE, Tu, Z, Weiser, JN, Bowdish, DME. MARCO is required for TLR2- and NOD2-mediated responses to Streptococcus pneumoniae and clearance of pneumococcal colonization in the murine nasopharynx. J Immunol. 2013 Jan 1;190(1):250Access the recommendation on F1000
  8. Whelan, FJ., Meehan, C., Golding, B., McConkey, B., Bowdish DME. The evolution of the class A scavenger receptors. BMC Evol Biol. 2012 Nov 27;12(1):227.
  9. DeWitte-Orr SJ, Collins SE, Bauer CM, Bowdish DM, Mossman KL. PLoS Pathog. An accessory to the ‘Trinity’: SR-As are essential pathogen sensors of extracellular dsRNA, mediating entry and leading to subsequent type I IFN responses. 2010 Mar 26; 6(3):e1000829.
  10. Bowdish D.M.E., Sakamoto K., Kim M,. Kroos M., Mukhopadhyay S., Leifer C.A., Gordon S., Russell D.G. Mycobacterial trehalose 6, 6’ dimycolate uses MARCO and TLR2 as co-receptors for macrophage activation. PLoS Pathogens. 2009 Jun;5(6):e1000474.
  11. Bowdish DM, Gordon S. Conserved domains of the class A scavenger receptors: evolution and function. (2009) Immunol Rev. Jan;227(1):19-31.