Trevor F. Moraes

Trevor F. Moraes

Associate Professor

BSc, Queen's University, 1993-1997
MSc, Queen's University, 1997-1999
PhD, University of Alberta, 1999-2004
Postdoc, University of British Columbia, 2004-2009

Address MaRS Center, West Tower
661 University Ave., Rm 1613
Toronto, ON M5G 1M1
Lab Moraes Lab
Office Phone 416-946-3048

Dr. Moraes completed his undergraduate training in the  Department of Biochemistry at Queen’s University in 1997 and an MSc there with Dr. William Plaxton in 1999. He obtained his PhD in 2004 at the University of Alberta, supervised by Drs. Michael Ellison and J.N.Mark Glover, followed by post-doctoral studies with Dr. Natalie Strynadka at the University of British Columbia.  Dr. Moraes was hired in 2009 as an Assistant Professor and was recently awarded a Tier II Canada Research Chair in the Structural Biology of Membrane Proteins (2012).  He has been an Associate Professor in the Department of Biochemistry since 2014.

In the News

Research Lab

Our lab focuses on the structural and functional characterization of protein and ion translocation machineries within the membranes of pathogenic bacteria. We use primarily X-ray crystallography in combination with other molecular approaches to gain a detailed understanding of how these membrane protein complexes function.

Learn more: Moraes Lab

Research Description

Membrane Protein Structural Biology

Proteins and small molecules are translocated across lipid bilayers by integral membrane proteins that span the bilayer and facilitate translocation. My lab centers around determining the atomic resolution structure of membrane proteins and complexes that function to transport materials across lipid bilayers. The primary focus of research in the lab is nutrient uptake mechanisms within Gram negative bacterial species. In addition to the structural and biochemical characterization of these ion transport system components, research in my lab also examines the membrane protein complexes that facilitate the proper insertion and assembly of these membrane protein transport components including surface anchored lipoproteins.

The Phospho-charbohydrate specific transporter AfuABC

Fig 1 structureDisease-causing bacteria depend on the acquisition of a diverse set of nutrients from their hosts to engage in successful pathogenesis. AfuABC binds and transports a particular set of phosphorylated carbohydrates (glucose-6-phosphate, fructose-6-phosphate and sedoheptulose-7-phosphate). AfuABC is conserved across bacteria, including a large number of Gram-negative pathogens such as Vibrio cholerae, Haemophilus influenzae and Citrobacter rodentium. AfuABC can mediate sugar-phosphate transport into bacteria and C. rodentium lacking AfuA are significantly impaired in competitive growth within the mammalian gut indicating that AfuABC based recognition and uptake of sugar-phosphates within the intestinal lumen plays a critical role during infection.

Slam-dependent surface lipoprotein translocation within Neisseria meningitidis

Slamfig_dept_website Lipoproteins decorate the surface of many obligate host restricted Gram-negative bacterial pathogens, playing essential roles in immune evasion and nutrient acquisition. In Neisseria spp., the causative agents of gonorrhea and meningococcal meningitis, surface lipoproteins (SLPs) such as factor H-binding protein (fHbp) and transferrin binding protein B (TbpB) are required for virulence and are primary targets for broad-spectrum vaccine development since they elicit bactericidal antibodies.  The surface lipoprotein assembly modulator (Slam) is required for the proper assembly of SLPs on the surface of Gram negative bacteria and is required for virulence. The mechanism of Slam and the translocation of SLPs is fundamental for the survival of these host restricted bacteria.

Iron acquisition through the bacterial transferrin receptor

In the vertebrate host, the level of free extracellular iron is well below that required to support the growth of bacterial pathogens, largely owing to the iron-sequestering effects of iron-binding glycoproteins transferrin and lactoferrin. Successful bacterial pathogens have developed high-affinity iron uptake systems capable of acquiring iron from transferrin and lactoferrin. Members of the Neisseriacea and Pasteurellaceae family including Neisseria meningitidis and Haemophilus influenza possess receptors consisting of the surface exposed lipoprotein TbpB and the integral outer membrane protein TbpA that bind transferrin and are involved in the retrieval and transport of iron across the outer membrane. Within the periplasm, the ferric binding protein, FbpA, binds iron and escorts it to the inner membrane ABC transporter where it is transported into the cytoplasm (Figure 1).

Phosphate specific transport and the Pho Regulon within Pseudomonas aeruginosa

Phosphate plays an essential role in nearly all metabolic, catabolic, and signaling events within virtually all living organisms. As such, the trafficking of phosphate anions is an immensely important function, yet the specific mechanism utilized to transport inorganic phosphate molecules across a lipid bilayer remains unclear. The Gram negative bacterial cell utilizes a double membrane system and employs a plethora of channels that can be constitutive or specifically expressed in its outer membrane (OM) in response to various environmental conditions. Most bacteria, including Pseudomonas react to environmental conditions of low phosphate by turning on a gene regulon leading to the expression of a number of phosphate trafficking proteins (Figure 2). This regulation is mediated by regulatory proteins anchored in the inner membrane (PhoR), that sense phosphate levels through an as yet uncharacterized interaction with the inner membrane transport complex.


View all publications on PubMed

Slam is an outer membrane protein that is required for the surface display of lipidated virulence factors in Neisseria
Y. Hooda, C.C. Lai, A. Judd, C. Buckwalter, H.E. Shin, S.D. Gray-Owen, and T.F. Moraes.
Nature Microbiology 1 (2016).  Read

A method for measuring binding constants using unpurified in vivo biotinylated ligands.
Anastassia K. Pogoutse, Christine C. Lai, Nick Ostan, Rong-hua Yu, Anthony B. Schryvers, Trevor F. Moraes.
Anal Biochem. 2016 Feb 17.  Read

The molecular mechanism of Zinc acquisition by the Neisserial outer-membrane receptor ZnuD.
Charles Calmettes, Christopher Ing, Carolyn M. Buckwalter, Majida El Bakkouri, Christine Chieh-Lin Lai, Pogoutse A, Scott D Gray-Owen, Régis Pomès and Trevor F. Moraes.
Nature Communications 2015 Aug 18;6:7996.  Read

Active Transport of Phosphorylated Carbohydrates Promotes Intestinal Colonization and Transmission of a Bacterial Pathogen.
Brandon Sit, Shauna M. Crowley, Kirandeep Bhullar, Christine Chieh-Lin Lai, Calvin Tang, Yogesh Hooda, Charles Calmettes, Husain Khambati, Caixia Ma, John H. Brumell, Anthony B. Schryvers, Bruce A. Vallance, and Trevor F. Moraes.
PLoS Pathog. 2015 Aug 21;11(8):e1005107. doi: 10.1371  Read

Nonbinding site-directed mutants of transferrin binding protein B enhances their immunogenicity and protective capabilities.
Frandoloso R, Martínez-Martínez S, Calmettes C, Fegan J, Costa E, Curran D, Yu R, Gutiérrez-Martín CB, Rodríguez Ferri EF, Moraes TF, Schryvers AB.
Infect Immun. 2014 Dec 29  Read

A substrate access tunnel in the cytosolic domain is not an essential feature of the solute carrier 4 (SLC4) family of bicarbonate transporters.
Shnitsar V, Li J, Li X, Calmettes C, Basu A, Casey JR, Moraes TF, Reithmeier RA.
J Biol Chem. 2013 Nov 22;288(47):33848-60  Read

The structural basis of transferrin sequestration by transferrin-binding protein B.
Calmettes C, Alcantara J., Yu RH, Schryvers AB, Moraes T.F.
Nat Struct Mol Biol. 2012 Feb 19;19(3):358-60.  Read

Bacterial receptors for host transferrin and lactoferrin: molecular mechanisms and role in host-microbe interactions.
Morgenthau A, Pogoutse A, Adamiak P, Moraes TF, Schryvers AB.
Future Microbiol. 2013 Dec;8(12):1575-85.  Read

Membrane transport metabolons.
Moraes TF, Reithmeier RA.
Biochim Biophys Acta. 2012 Nov;1818(11):2687-706.  Read

Structural variations within the transferrin binding site on transferrin-binding protein B, TbpB.
Calmettes C, Yu RH, Silva LP, Curran D, Schriemer DC, Schryvers AB, Moraes TF.
J Biol Chem. 2011 Apr 8;286(14):12683-92  Read

Insights into the bacterial transferrin receptor: the structure of transferrin-binding protein B from Actinobacillus pleuropneumoniae.
Moraes TF, Yu RH, Strynadka NC, Schryvers AB
Mol Cell. 2009 Aug 28;35(4):523-33.  Read

An arginine ladder in OprP mediates phosphate-specific transfer across the outer membrane.
Moraes TF, Bains M, Hancock RE, Strynadka NC.
Nat Struct Mol Biol. 2007 Jan;14(1):85-7.  Read