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Professor

Trevor Moraes

Membrane proteins, Neisseria spp., X-ray crystallography

PhD

Location
MaRS Discovery Centre - West Tower Floor 15/16
Address
661 University Ave., Rm. 1613, Toronto, Ontario Canada M5G 1M1
Research Areas
Computational Biology, Membranes and Transport Mechanisms, Microbiology, Molecular Medicine and Drug Discovery, Protein Structure and Dynamics
Role
Faculty
Accepting
Graduate Student Rotations - Current Term - Please Enquire, Undergraduate Research - Summer - Please Enquire, Undergraduate Research - Fall and Winter - Please Enquire

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 has had an active research lab in the Department of Biochemistry since 2009. 

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. 

Slam-dependent surface lipoprotein translocation  

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. 

Nutrient transport across the Gram-negative cell Envelope 

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. 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. 

 

Appointments, Cross Affiliations, Memberships 

Graduate Coordinator, Department of Biochemistry 

Courses Taught 

BCH 2101H Scientific Skills for Biochemists 
BCH374Y1 Research Project in Biochemistry 
JBB2025H Protein Crystallography 
BCH473Y Advanced Research Project in Biochemistry 
BCH478H Advanced Biochemistry Lab 
BCH2022Y Doctoral Seminar Course in Biochemistry 
BCH2020Y Master's Seminar Course in Biochemistry 

Awards and Distinctions 

2012-2022 — CRC tier II Canada Research Chair in Membrane Protein Structural Biology 
2014-2018 — Early Researcher Award