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Biomolecular Magnetic Resonance Facility
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Peptide dragging water molecules into a membrane bilayer & destabelizingWater conduit through Human heme oxygenasePulse program for simultaneous detection of all MQ coherencesDynamic ring opening mechanism of Jadomycin

Ray Syvitski, Ph.D. UBC

Bio-Macromolecular & Analytic Chemical NMR Researcher

Former Adjunct Chemistry Professor @ Dalhousie University
Former Adjunct Biochemistry Professor @ Dalhousie University
Executive Editor for Cell Biology Research & Therapy
Editor for Journal of Proteomics and Computational Biology
Editor for Journal of Analytical & Molecular Techniques

E-mail:
Phone:
Address:
Ray.Syvitski@dal.ca
(902) 850-2425
BioMolecular Consulting
21 Sandstone Drv.
Hatchet Lake, NS
Canada, B3T 1P7
 
The BMRF houses 700 & 500 MHz NMR Spectrometers with two cryoprobes 1.7 and 5 mm, and an HRMAS system.



After over 20 years of scientific research and being a university educator, I have taken the opportunity to start a new business venture to help promote and develop children's education. With my math, physics, chemistry and biochemistry background I am designing and manufacturing  fun-to-play-with children's educational wooden toys.  WoodChaCallIt helps parents, grandparents and caregivers nurture children's creativity, teach a scientific concept or spend quality time with the child through innovative educational wood toys and woodcrafts. All the hand-crafted toys are made in Canada and are durable and safe.

Research Projects:

By applying and developing magnetic resonance spectroscopy, molecular dynamics (MD) computer simulation, and other physical techniques (e.g. cryo-TEM), my research program is designed to investigate the relationship among structure, dynamics, electrostatic interactions and function of macromolecules and/or macromolecular assemblies. Macromolecules include proteins and peptides whereas macromolecular assemblies refer to liquid crystals including biological membranes.

My research program involves a number of projects:
  • MD simulations of liquid crystals and 

    Antimicrobial peptides (AMPs)

  • Structural characterization of bio-molecules

  • NMR methodology development

    • Quantitative NMR

    • HRMAS characterization of whole cell algae

    • Drug/protein binding pocket characterization

Sorry, I am not accepting students.

AMPs:
A wide variety of AMPs have been isolated from many plants and animals. AMPs in general are very effective at killing bacteria, enveloped viruses, parasites, and tumour cells. Furthermore, bacteria have difficulty developing resistance towards AMPs. Thus, AMPs are being considered as potential alternatives to current antibacterial agents particularly with the emerging problem of drug-resistant pathogenic bacteria. AMPs destabilize bacterial membranes. Slight amino acid mutations can cause significant alterations in activity, and general theories for AMP activity range from membrane carpeting to pore formation models that allow essential ions and metabolites to leak out.
AMP in DPC (A) and DPC/SDS (B) micelles. The AMP forms a regular helix only in DPC/SDS.
The AMP associates with DPC (A) and DPC/SDS (B) micelles. However, it only forms an alpha helix when associated with DPC/SDS micelles that are a mimic for bacterial membranes. [Biochemistry, (2005) 44, 7282-7293].
Activities of AMPs are roughly correlated with the amphipathic and cationic nature of the peptides. However, there is no clear connection between the structure and mechanism of AMP activity. We are determining the structure, dynamics and multimerization propensity of AMPs using MD simulations in the presence of the lipid-like environments, in order to understand their mode of action.

MD Computer Simulations:

Computer simulations are an excellent method for bridging the gaps between experiment and theory. We are conducting a comparative study to investigate peptide/membrane/water interactions of model membranes, and peptides that cause membrane destabilization, e.g. AMPs, and the active peptides of cell-to-cell FAST proteins. Although AMPs cause cell lysis, and fusion proteins cause membrane fusion, the initial stages of their mechanisms may be similar i.e. the proteins/peptides must initially destabilize the membrane which involves restructuring of the lipids and water molecules at the lipid surface. Regardless, the research will advance the knowledge and understanding of the mode of action of AMPs, fusion proteins and provide direction for future studies that will extend to antifreeze peptides, MA receptor proteins, antibiotics, and ion channel peptides.
AMPs can span a membrane bilayer. Their destabelization properties may be related to their abiltiy to bring water into the hydrophobic core of the membrane.
From MD simulations, AMPs can span a phospholipid membrane. The membrane phosphate head group is represented by spheres. Phosphate head groups from POPC that are in proximity to the peptide are shown in tan and phosphate head groups from then anionic POPG are  shown in orange. The AMP can destabilize biological membranes by sequestering waters and charged phosphate head groups into the hydrophobic core of the membrane.

Structure Characterization of Bio-Molecules::

Bio-molecules  can range from  proteins and peptides through to secondary metabolites and toxins. Our group has focused on structural and dynamic characterization of proteins and peptides. Current investigations involve characterization of a 15N and 15N/13C labelled toxic peptide from the Northern Short Tail Shrew that is 100 time more potent than scorpion venom.


Active peptide in scorpion venom
Peptide that composes scorpion venom

NMR Method Development:

Many of the projects are focused on NMR spectroscopic method development. This ranges from multiple quantum spectral acquisition and analysis of orientationally ordered molecules [J. Mag. Res. (2002) 155, 251-256, NMR of Ordered Liquids, Burnell, E.E and de Lange, C.A. editors. Kluwer Academic, Dordrecht, The Netherlands], DOSY analysis for molecular mass distribution of complex polysaccharides [Biomacromolecules (2006) 7, 2368-2376], quantitative analysis of complex biofluids, and metabolnomics.



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