My research is focussed on applying mass-spectrometry (MS) based proteomics to study induced pluripotent stem cells (iPSCs) and T cells. Part of the research focus involves establishing computational approaches to analyse large scale datasets. This includes rigorous analysis of the limitations of the known proteomics methods, as well as strategies to mitigate their inadequacies, such as consequences of batch effects within the large-scale data as described in my MCP manuscript(1).
Figure 1 Multibatch TMT reveals false positives, batch effects and missing values.
On the iPSC front I aim to define human induced pluripotent stem cells (iPSCs) proteome and then use iPSCs as model for studies on X-linked disease and gender differences. One of the initial points of interest is the proteomic analysis of erosion of X chromosome inactivation (XCI).
XCI is a dosage compensation mechanism for X chromosome gene products which is developmentally vital, as failure to induce XCI can be embryonically lethal. Errors in the process have been documented, as genes can escape this inactivation leading to documented X-linked disease. iPSCs are particularly interesting as they have been shown to suffer from loss and erosion of XCI, providing a good model for dosage related X-linked disease. This process has only been studied at the RNAseq level, with no work being done on the effector molecules, the proteins. I believe studying the effects of erosion of XCI at the protein level will truly enable us to understand the consequences of erosion of XCI.
Being part of the Cell Signalling and Immunology division, and with keen interest in T cells, I am also involved in a large-scale interdisciplinary project whose objective is to define the haematopoietic proteomes within mice and humans. As part of this project I have developed the Immunological Proteomics Resource (immpres.co.uk), an open access publicly available resource encapsulating our immune cell proteomes. As a follow-up I also aim to define at the proteomic level the sex specific differences within T cells, to understand how they affect their effector functions and how those translate into differential disease risk for males and females.