marc.wilkins@unsw.edu.au

Projects Available for PhD, Honours and Practicum students:

Dynamics of the Interactome

We study the proteins inside the cell on a global scale, and how they interact. We have a particular interest in how protein-protein interactions change, particularly in association with human disease. It is already known that many cancers, such as prostate cancer, colon cancer and  familial melanoma are caused by the loss or gain of protein-protein interactions and it is likely that many other diseases stem from similar types of defects. This area of research may hold vital clues to how small molecules (drugs) can ultimately be used therapeutically to block or mimic disease-associated protein-protein interactions.

To study protein-protein interactions on a large scale, we use advanced protein separation and analysis methods as well as sophisticated bioinformatics. We are one of a few laboratories in Australia undertaking this type of investigation. Our laboratory is a multidisciplinary research environment, containing researchers with expertise in proteomics, bioinformatics and systems biology.

Project 1:  How can we detect changes in protein-protein interactions?

We know that most proteins inside the cell do not function by themselves; instead they function as part of protein complexes. However, we have a poor understanding of how complexes can change in their protein composition, and how individual proteins can change their interactions. We have recently developed new technology for the large-scale purification and analysis of protein complexes. This results in the separation of hundreds of complexes from eukaryotic cells. We can now combine this technology with differential display techniques. This will give us some of the first glimpses on the dynamics of  protein-protein interactions in the cell. This will first be trialled in S. cerevisiae, then applied to the study of diseased human cells and tissues.

There are different aspects of this project that are available for student projects.
a) Proteomics students - skills you will learn are state of the art techniques of: proteomics, protein complex purification, MALDI-TOF and ESI-MS mass spectrometry for protein identification and characterisation, cell culture and general bioinformatics.
b) Bioinformatics students – the project generates and analyses complex proteomic data that requires sophisticated bioinformatics. The visualisation of these protein complexes is of central importance to this work, and we have adapted the GEOMI visualisation software platform for our work. Bioinformatics projects for this area are also detailed under the Honours projects listings in Computer Science & Engineering.

Project 2:  What is the role of post-translational modifications in the protein-protein interaction network?

We have built global protein interaction networks using the GEOMI software. This has shown us that proteins participate in a stunning number and variety of interactions inside the cell. What is the role of post-translational modifications here? It is known that certain interactions can only occur when particular amino acids carry certain modifications. For example, a protein carrying an SH2 domain will only be able to interact with another protein that has a particular phosphorylated (but not unphosphorylated) tyrosine residue. However, the extent to which this molecular switch is used to control the assembly and disassembly of protein complexes - and thus control protein function, is not known. It is our hypothesis that modification-dependent interactions serve as a fundamental method for controlling protein complexes and protein function, but this needs to be proven. This project will do proteome-wide screeens for reversible post-translational modifications such as methylation and acetylation, and map these on to the protein interaction network. We will consider where the modified amino acids are found, and the domains present in any interaction partners. We may examine mutant strains or cell lines to better understand this.

There are different aspects of this project that are available for student projects.
a) Proteomics –  skills you will learn are state of the art techniques of: proteomics, post-translational modification analysis, MALDI-TOF and ESI-MS mass spectrometry for protein identification and characterisation, cell culture and general bioinformatics.
b) Bioinformatics – networks need to be constructed to consider all known post-translational modifications in the context of protein-protein interactions. Skills you will learn will include network construction, visualisation and domain analysis. The analysis of mass spectrometric data may also be required.   

Interested?

Please contact Marc if you are interested in these projects. References and reading are available on request, and theses from previous students can be browsed in the lab.