Mr Tom Williams (PhD Student)
Contact Details:
Email: williath@tcd.iePhone: +353 (0) 1 8962873
Evolution of molecular chaperones and their clients
Research project: Living cells are absolutely crammed with proteins. To do its job, each protein must fold into the proper shape. Under ideal conditions, most proteins can manage this on their own, but conditions in the cell aren’t ideal. Without help, many newly formed proteins clump together, forming aggregates which could damage the cell or cause disease. The primary job of molecular chaperones is to help the other proteins in the cell fold properly, even in a hostile environment. This role becomes even more important when cells suffer from heat or other stresses, when it becomes especially difficult for proteins to fold normally. Stressed cells overexpress chaperones as a protective measure, hence their other name: heat shock proteins.
We are studying the role of chaperones in evolution from two perspectives. Firstly, through the duplication and functional divergence of chaperones in the tree of life. GroEL (pictured) is an essential chaperone in Escherichia coli and other bacteria. It consists of two back-to-back rings of seven identical subunits. The related complex in eukaryotes consists of eight different subunits whose substrate-binding (and other) properties vary. Similarly, bacteria get by with one or a small number of copies of the chaperone Hsp70, while eukaryote genomes encode different Hsp70 proteins for each cellular compartment and several for the cytosol. An interesting question is whether these duplicated chaperones have taken on new eukaryote-specific functions, or whether their abundance simply reflects the process of weakened selection and subfunctionalization that has lead to the shambolic genomes of modern eukaryotes. In pursuit of this question, we have developed a fast new computational method for detecting significant functional divergence on a large scale, within genomes or across a phylogenetic tree.
Secondly, we are approaching the role of chaperones in evolution through the client proteins they help fold. Previous experimental work has suggested that chaperone clients accumulate mutations differently to non-clients, and may also prefer different folds. I am attempting to further this work computationally in order to understand how chaperones affect the evolution of the proteins they interact with.
Figure 1: GroEL/GroES complex by David S. Goodsell, based on PDB ID 1AON.
Other scientific interests:
(These are other areas of biology which I find very interesting, but which are not directly related to my thesis). The early evolution of the cell and the divergence of the main lineages of life; the evolution of translation; replicating proteins and catalytic RNAs; the biodiversity of bacteria.
Publications
- Williams T.A., Wolfe K.H., and Fares M.A. (2009) No Rosetta Stone for a sense-antisense origin of aminoacyl tRNA synthetase classes. Mol Biol Evol 26: 445-50.
- Christina Toft, Tom A. Williams and Mario A. Fares. 2009. Genome-Wide Functional Divergence after the Symbiosis of Proteobacteria with Insects Unraveled through a Novel Computational Approach. PLoS Comput Biol 5(4); e1000344
- Williams T.A., Codoner F.M., Toft C., Fares M.A. (2010) Two chaperonin systems in bacterial genomes with distinct ecological roles. Trends Genet: 26: 47-51.
