Our laboratory studies protein-protein interactions and the networks that these interactions function within. Protein-protein interactions are often altered in disease through mutation, disrupting the underlying networks. Our interest is to understand how mutations in cancer disrupt protein interaction networks. We study the networks of interacting proteins that carry out fundamental cellular processes such as signal transduction. We are interested in ‘mapping’ these interactions in cancer cells, to understand how cancer subverts normal cellular functions. A particular interest is the Wnt signaling pathway, an important signal transduction pathway during animal development and in cancer.
We use large-scale proteomics and transcriptomics techniques to identify and quantify thousands of proteins or RNAs once, so that we gain a comprehensive view of how gene and protein expression is regulated. Affinity-purification mass-spectrometry (AP-MS) is a key technique that allows us to identify the interacting partners of a protein of interest. This technique first isolates a target protein using an antibody and then uses mass-spectrometry to identify the proteins that are associated with the target protein. By studying these interacting partners, we can gain insight into what the function of the protein is. By studying the interacting partners of a mutant protein we can understand what happens in the cell when proteins are mutated. We use these techniques in cancer cells to understand which mutations drive cancer.
Computational / Bioinformatics Approaches
Computational (bioinformatics) techniques are an essential tool when dealing with the large-scale data tha result from omics experiments. Programming languages such as Python, Perl and R are powerful tools that can be used to process, analyze, integrate and visualize molecular data. We are also interested in applying techniques of Big Data analysis in molecular biology. This video was made by undergraduate students working with us.
What will I gain from working in this lab?
You will gain experience in cutting-edge research as well as becoming familiar with molecular biological, proteomic and computational approaches.
Reading lists for our laboratory are here
See papers and reviews in:
- β-catenin mutant signaling network. β-catenin is an important oncoprotein in many different cancers, and is also a critical component of the Wnt signaling pathway. Our focus is on understanding how mutations that activate β-catenin alter protein interactions in the cell, and how these alteration lead to the fomation of tumours. We are using proteomic techniques to identify new partners of β-catenin in cancer cells.
- Novel oncoproteins and their interaction networks. In contrast to β-catenin, there are many candidate oncoproteins about which we know very little. We are targeting these proteins in our proteomics experiments to understand their protein-protein interactions and function in cancer cells
- Computational approaches to understanding protein-protein interaction networks. Integration and analysis of protein-protein interactions and other types of data such as gene-expression can reveal modules of proteins imporant in cancer. This project will develop and apply new bioinformatic approaches to protein-protein interaction networks.
Some example project titles from previous years
- An Investigation into the Interplay Between Wnt Signalling, DNA Methylation, and Cell-Cell Adhesion
- The investigation into the inhibitory nature of Canonical and Non-canonical Wnt Signalling in Colorectal cancer patients’ gene expression
- Investigating How Beta-Catenin is Regulated Across Prostate Tumour Samples