Professor Angus LamondFRS FRSE FMedSci

We are studying gene expression, RNA processing and disease mechanisms in human cells and model organisms. Our goal is to characterise structure/function relationships within the cell and to study protein dynamics at a systems level. We do this using a combination of quantitative techniques, including mass-spectrometry-based proteomics, cell and molecular biology, fluorescence microscopy and computational approaches for big data analytics and interactive data exploration.

The use of high throughput proteomics technologies provides a system-wide approach allowing us to measure cellular responses for a large number of proteins in parallel. An integral part of this work is the development of new software tools for the management analysis and visualisation of complex proteomics data sets.

To increase the value of the comprehensive proteomic data sets we have generated, we have incorporated all of our data into an open access, searchable online database, the Encyclopedia of Proteome Dynamics {Brenes:2017vl} (EPD) The EPD provides multiple interactive visualisations, allowing for convenient searching and interactive exploration of all the processed proteomics data. It also provides links to download both the processed data and associated raw MS files, the latter having been deposited in the ProteomeXchange PRIDE repository. The data visualisations in the EPD can be explored by clicking on selected data points, which reveals tooltips providing additional information and links to other related online data resources. Further, using the accompanying Search Box, each data visualization can be searched using multiple selectable criteria, including either proteins/genes of interest, GO terms, subunits of specific protein complexes or relation to functional pathways. Identified components can be readily highlighted and the resulting annotated visualization also downloaded and saved as an editable .svg file. For more detailed descriptions of the functionality and use of the EPD, see Brenes et al., 2017.

In our recent studies we have used combined proteomics, cell biology, microscopy and biochemical approaches in projects including, (i) to characterize the regulation of gene expression during physiological cell cycle progression (ii) to characterize human iPS cells and study genetic variation in the human population, (iii) to study proteome remodeling when healthy human cells are transformed into cancer cells by oncogene activation and (iv) we have used nematodes to study how gene and protein expression responds to acute starvation. In addition, we have studied biochemical mechanisms involved in pre-mRNA processing and alternative RNA splicing and have identified novel small molecule modulators of alternative splicing.