Abstract

From protein interactions to gene expression distributions

The work in my group is focused on the evolution and dynamics of protein interactions and transcriptional regulatory interactions. In these two areas, we analyse large datasets using computational and mathematical methods.

In the first part of my presentation, I will talk about our work on the evolution and assembly of protein complexes. We surveyed three-dimensional structures of protein complexes to identify interface size as a determining principle of both evolutionary and assembly pathways (Levy et al., Nature, 2008), and to quantify conformational change in assembly (Marsh & Teichmann, Structure, 2011). In recent work, we show for the first time, the importance of promiscuous protein interactions in determining a protein’s surface residue composition (Levy et al., in preparation). These new insights have implications for structure prediction and protein engineering.

In the second part of my presentation, I will talk about our work on dissecting the distribution of gene expression levels in mammalian cell populations, revealing two distinct mRNA abundance classes (Hebenstreit et al., Mol Sys Biol, 2011). We provide evidence, including correlation of the two mRNA abundance classes with epigenetic modifications (Hebenstreit et al., Nucleic Acids Res, 2011), supporting the notion that these two classes correspond to functional versus non-functional proteins in cells. These findings now help interpret mRNA and protein abundance data in the form of microarrays, RNA -sequencing and proteomics.

References

Levy, E.D., Boeri-Erba, E., Robinson, C.V. & Teichmann, S.A. (2008) Assembly reflects evolution of protein complexes. Nature, 453, 1262-5.

Marsh, J. & Teichmann, S.A. (2011) Relative solvent accessible surface area predicts protein conformational changes upon binding. Structure, 19(6):859-67.

Hebenstreit, D., Fang, M., Gu, M. Charoensawan, V., van Oudenaarden, A. & Teichmann, S.A. (2011a) RNA sequencing reveals two major classes of gene expression levels in metazoan cells. Mol. Sys. Biol., 7:497.

Hebenstreit, D., Gu, M., Haider, S., Turner, D., Lio, P. & Teichmann S.A. (2011b) EpiChIP: gene-by-gene quantification of epigenetic modification levels. Nucleic Acids Res., 39, e27.