Angus Lamond

Gene Regulation & Human Disease Mechanisms

Many forms of human disease result from the misregulation of one or more genes that consequently alter how cells behave; for example altering metabolism and/or affecting the rate of cell division and cell movement. In most cases this is due to differences in the complex array of proteins made by diseased cells, as compared with healthy cells. We therefore are developing methods that allow us to identify in detail the full set of proteins that cells make under different growth conditions and in parallel we are developing new computational software to help us analyse and understand the resulting large volume of data that our experiments generate.

We use a multidisciplinary approach to study the regulation of gene expression and human disease mechanisms. Our research combines quantitative approaches, including mass spectrometry-based proteomics, microscopy and computational methods for ‘big data’ analytics. We are studying biochemical mechanisms regulating key biological processes, including alternative splicing of messenger RNA precursors, cell cycle progression, stress responses and stem cell differentiation. A focus of our current work is on identifying common effectors of invasion and metastasis that are activated by oncogenes and epigenetic mechanisms affecting phenotypes in transformed cells. This includes detailed analysis of differential protein expression in immune cell subtypes and cancer cells, in both human and mouse models. We are also studying human iPS models that can be differentiated in culture and engineered with clinically relevant mutations. Another focus for my current research is the characterisation of drug-like, small molecule pre-mRNA splicing modulators we have identified. A major component of our research is the development of innovative computational tools for the management, visualisation and analysis of research data and metadata. We have created state of the art data management and analysis tools featuring custom designed, user-friendly graphical interfaces (see; www.peptracker.com/epd). Our computational tools make extensive use of innovative technologies created in the commercial domain for big data transactions that we have adapted to provide novel solutions for interactive data analysis and sharing.