Proteomic analysis of gingipain catalysed transpeptidation reactions and its relevance to autoimmunity

Research Opportunity
Honours
Number of Honour Places Available
1
Number of Master Places Available
1
Department
Melbourne Dental School
Location
Bio21 Molecular Science and Biotechnology Institute
Primary Supervisor Email Number Webpage
A/Prof Paul Veith pdv@unimelb.edu.au
Co-supervisor Email Number Webpage
Dr Lianyi Zhang

Summary This project will study in detail the degradation pathway of human haemoglobin to help predict the kinds of favoured transpeptidation reactions that may also occur in vivo.

Project Details

The gingipains are cell surface cysteine proteases and major virulence factors of Porphyromonas gingivalis, a keystone pathogen of human periodontitis (gum disease). We recently discovered that these proteases not only hydrolyse proteins but also cleave them via transpeptidation leading to rearranged peptide sequences. In vivo, this is expected to generate a staggering number of rearranged host protein sequences which may lead to autoimmune reactions. The aim of this project is to further characterise this transpeptidation activity. First, transpeptidation rates will be measured as a function of environmental variables such as pH and temperature as well as a function of the sequence and length of peptide acceptors. In addition, we have noted that gingipains degrade model substrates including human haemoglobin via both transpeptidation and hydrolysis reactions in vitro. This project will study in detail the degradation pathway of human haemoglobin to help predict the kinds of favoured transpeptidation reactions that may also occur in vivo. Finally, a proteomic study of sub-gingival plaque and surrounding protein fluid (gingival crevicular fluid) obtained from periodontitis patients will be conducted to identify in vivo targets of transpeptidation.




Research Opportunities

Honours
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Melbourne Dental School

Research Node

Bio21 Molecular Science and Biotechnology Institute

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