Proteomic Mapping and Molecular Modelling of Avian H5N1 Influenza Antigen Epitopes Targeted by Human Antibodies

Summary

In studying Avian H5N1 Influenza specific Antibodies within Humans the aim is to clearly and definitively identify the respective viral proteins and epitopes targeted by neutralizing Antibodies through i) epitope mapping and ii) molecular modelling.

Supervisor(s)

Dr Garry Lynch

Research Location

Camperdown - Central Clinical School

Program Type

Masters/PHD

Synopsis

Background Topic:We have identified Human antibodies in the population that bind to Avian H5N1 Influenza proteins. Needed is unequivocal resolution of the avian H5N1 proteins targeted by cross-reactive Human anti-influenza Antibodies, and a definition of the respective linear and conformational epitopes involved. Using proteomic based procedures we aim to definitively identify and map the H5N1 protein epitopes targeted by neutralizing Human Anti-Influenza Antibodies by;

1. Epitope Mapping
   1. Using Proteomics map the H5N1 proteins targeted by Human antibodies (Ab)
   2. Ab binding to native viral proteins, synthesized peptides and recombinant proteins.
   3. A profiling the linear and conformational protein epitopes targeted by Human Abs.
2. Molecular Modelling
   1. Model and compare the protein structures of Human Influenzas with Avian H5N1 strains for: Their respective Haemagglutinin, Neuraminidase, NP, NS2, M1, M2 proteins
   2. Identify the HA & NA regions and structures conserved in Human & Avian Influenzas.
   3. Map the conserved protein surfaces and identify the functionally important protein regions to which Antibodies may target.
   4. Use the information gained to inter-phase with the direct experimental studies in topic 1 to identify and predict sites for Antibody therapy design.

This has considerable importance for understanding natural immunity for Avian H5N1 Influenza in the community and for identification of the molecular structures involved and their therapeutic potential as targets.Collaborations:This project will be co-supervised by Dr Brett Chuch and Associate Professor John Sullivan.

Additional Information

Techniques can involve:Molecular modelling, cell and protein fractionation, cell culture, electrophoresis, mass spectrometry, immonoblotting, immunoprecipitation, flow cytometry and multiplex-analyses; viral neutralization and cytokine binding assays.

Keywords

Viral Infection, Infectious Disease, Pandemic Disease, Pandemic, Avian Influenza, Hemagglutinin, Neuraminidase, H5N1, Proteomics, molecular modelling, Protein Structures, Infectious diseases, Infection & immunity

Opportunity ID

The opportunity ID for this research opportunity is: 229

Other opportunities with Dr Garry Lynch

• ASSESS THE GP GLYCOPROTEIN STRUCTURES OF EBOLA AND MARBURG VIRUS ENVELOPES, THEIR MUCIN-LIKE DOMAINS AND SITES FOR IMMUNE ATTACK
• STUDIES OF VARIABLE OR CONSERVED SURFACE PROTEIN SITES OF NEISSERIA MENINGITIDIS AS EPITOPES FOR STRAIN-SPECIFIC VACCINES OR BROAD-STRAIN (UNIVERSAL) VACCINES
• Display of Viral Surface Glycoprotein on Virus like particles (VPLS) for Structure and Immune Epitope Discovery