Sarah Teichmann, MRC Laboratory of Molecular Biology, Cambridge, UK

Biomolecular Network Evolution
The lectures will be structured according to the following schedule: Transcriptional regulatory networks; Protein complexes and protein interaction networks; Human genome evolution and network evolvability. The biological characteristics of an organism emerge, in large part, as a result of the dynamic inter-play between its gene repertoire and the regulatory apparatus, which includes transcription factors and signal transducers.

In Lecture 1, the evolutionary histories and the dynamics of transcriptional regulatory systems from a network perspective will be reviewed. Transcription factors act through protein-DNA interactions, but perhaps even more important in the cell are protein-protein interactions.

In Lecture 2, the publicly available data on protein interactions and protein complexes will be surveyed, both from conventional small-scale experiments collected over the decades, including three-dimensional structures, and more recently by large-scale functional genomics experiments. How have this particular class of interactions evolved, and how do they fold and assemble? These questions will be addressed during the talk.

In Lecture 3, the sequence divergence rates of different functional categories in the human genome will be studied, and try to understand these in the context of the larger network of interactions in a metazoan cell at different evolutionary timescales.

Teichmann , S.A. & Babu, M.M. (2004). Gene Regulatory Network Growth by Duplication. Nature Genet ., 36 , 492-496.

Luscombe , N.M. , Babu, M.M., Yu, H., Snyder, M., Teichmann , S.A. & Gerstein, M. (2004). Genome-scale analysis of regulatory network dynamics. Nature , 431 , 308-312.

Han, J.-H., Kerrison , N.D. , Chothia, C. & Teichmann , S.A. (2006). Divergence of inter-domain geometry in two-domain proteins. Structure , 14, 935-945.

Han, J.-H., Batey, S., Nickson, A.D., Teichmann , S.A. & Clarke, J. (2007). The folding and evolution of multidomain proteins. Nature Rev Mol Cell Biol , 8, 319-330.

Wright, C.,F., Teichmann , S.A. , Clarke, J. & Dobson, C.M. (2005). Aggregation and evolution of multi-domain proteins: the importance of sequence identity. Nature , 438, 878-881.

Pereira-Leal, J., Levy, E.D., Kamp, C. & Teichmann , S.A. (2007). Evolution of protein complexes by duplication of homomeric interactions. Genome Biol , 8 , R51.

Pereira-Leal, J. & Teichmann , S.A. (2005). Novel specificities emerge by step-wise duplication of functional modules. Genome Res ., 15, 552-559.

Levy, E., Pereira-Leal, J., Chothia, C & Teichmann , S.A. (2006). 3DComplex: a structural classification of protein complexes. PLoS Comp Biol ., 2 , e155.