Toby Gibson

As from 1996, I have been responsible for establishing an in-house Sequence Analysis Service to support the EMBL research groups. Aidan Budd, Sophie Chabanis-Davidson, Chenna Ramu , Christine Gemünd, José Castresana, Rune Linding work with me. We maintain several web servers, including SRS (Sequence Retrieval Service), Gene2EST and a fast and sensitive Bioccelerator database search facility. We also run in-house courses on using EMBL's computational facilities. If you have some sequence analysis needs, come and talk to us.

My research interests involve the application of computers in molecular biology. In recent years, this has centred primarily on amino acid sequence analysis. I have worked on a number of domains and proteins where divergent sequence relationships have been informative, often in collaboration with structural groups who have solved several of the domain structures. Annalisa Pastore's group at Mill Hill have solved the structure of Frataxin, which is involved in the Inherited disease Friedreich's ataxia. With Rein Aasland, I have been interested in looking at chromatin-associated domains, such as the PHD finger and the SAND domain. Michael Sattler's group at EMBL have solved the DNA-binding SAND domain structure. With Jürg Spring, I have been looking at redundant genes in vertebrates, which seem to be differentially retained, depending on whether the phenotypes are dominant or recessive.

I am coordinator of an EU grant QLRI-CT2000-00127 which sets out our plans to develop a new protein motif database, the Eukaryotic Linear Motif resource, ELM (elm.eu.org). As well as EMBL, the other partners are Rein Aasland (Bergen), Bill Hunter (Dundee), Manuela Helmer-Citterich (Rome), Giulio Superti-Furga (CellZome) and Leszek Rychlewski (BioInfobank). There are many short functional motifs in modular proteins but it is difficult to provide good tools for their detection in query sequences due to a severe overprediction problem. The aim of the ELM project is to provide software filtering tools as well as the motif database, in order to reduce this problem. Filters currently include globular domain, cell compartment and taxonomy. The project is ongoing but you can use ELM now to search for functional sites in your protein or simply to browse the entries. Other servers from our group that are useful in conjunction with ELM are GlobPlot (find non-globular regions that may be rich in short motifs) and SIRW (select sets of proteins by kyword search to query with motif patterns).

Recently, I have been thinking about a nucleic acid agent for TSEs (spongiform encephalopathies). I have put forward a model, termed RuNAway Disease, for SINE retroposons as the transmissible agent with a mechanism to overproduce PrP, leading to amyloid plaque formation. Evidence for or against the model is scanty, but I hope to persuade TSE labs to do some testing. the RuNAway model has been posted on the GenomeBiology web set.

I have also been involved in some methods development projects. The multiple alignment programs Clustal W and Clustal X were developed together with Des Higgins (now at Cork) and Julie Thompson and colleagues (now in Strasbourg): we continue to maintain and develop Clustal W and X. Julie Thompson and I have also worked closely with Ewan Birney (now at the Sanger Centre) in the development of the WiseTools package of sequence comparison programs. WiseTools is a generalised sequence analysis system in which the user can compare combinations of proteins, profiles (from multiple alignments) and DNA translation frames. A frameshifting capability allows the user to match homologous proteins despite frameshifts caused by introns or sequencing errors.

More details may be found at our Official EMBL Team Page.

Recent Publications

Andrade, M. A., Ponting, C. P., Gibson, T. J. and Bork, P. (2000) Homology-based method for identification of protein repeats usingstatistical significance estimates. J. Mol. Biol., 298, 521-537.

Gibson, T. J. and Spring J. (2000) Evidence in favour of ancient octaploidy in the vertebrate genome. Biochem. Soc. Trans.,28, 259-264.

Hill, F., Gemuend, C., Benes, V., Ansorge, W. and Gibson, T. J. (2000) An estimate of large-scale sequencing accuracy. EMBO Reports, 1, 29-31.

Musco, G., Stier, G., Kolmerer, B., Adinolfi, S., Martin, S., Frenkiel, T.,Gibson, T. and Pastore, A. (2000) Towards a structural understanding ofFriedreich's ataxia: the solution structure of frataxin. Structure, 8,695-707.

Ramu, C., Gemünd, C. and Gibson, T. J. (2000) Object-oriented parsing of biological databases with Python. Bioinformatics, 16, 628-638.

Adinolfi, S., Bagni, C., Musco, G., Gibson, T., Mazzarella, L. and Pastore, A. (1999) Dissecting FMR1, the protein responsible for Fragile X syndrome, in its structural and functional domains. RNA, 5, 1248-1258.

Gibson, T. J. and Bork, P. (1999) "Encyclopedia of Molecular Biology" (Ed. T. Creighton) Wiley & Son Inc., New York, pp 86-90; 765-766; 961-962; 1252, 2320-2324.

Musco, G., de Tommasi, T., Stier, G., Kolmerer, B., Bottomley, M., Adinolfi, S., Muskett, F. W., Gibson, T. J., Frenkiel, T. A. and Pastore, A. (1999) Assignment of the 1H, 15N, and 13C resonances of the C-terminal domain of frataxin, the protein responsible for Friedreich ataxia. J. Biomol. NMR, 15, 87-88.

Zeller, R., Haramis, A. G., Zuniga, A., McGuigan, C., Dono, R., Davidson, G., Chabanis, S. and Gibson, T. (1999) Formin defines a large family of morphoregulatory genes and functions in establishment of the polarising region. Cell Tissue Res., 296, 85-93.

Gibson, T. J. and Spring. J. (1998) Genetic redundancy in vertebrates: polyploidy and persistence of genes encoding multidomain proteins. Trends Genet., 14, 46-49.

Gibson, T. J., Chenna, R., Gemuend, C. and Aasland, R. (1998) The APECED polyglandular autoimmune syndrome protein, AIRE-1, contains the SAND domain and is probably a transcription factor. (1998) Trends Biochem. Sci., 23, 242-244.

Jeanmougin, F., Thompson, J. D., Gibson, T. J., Gouy, M. and Higgins, D. G. (1998) Multiple sequence alignment with Clustal X. Trends Biochem. Sci., 23, 403-405.

Lock, P., Abram, C. L., Gibson, T. and Courtneidge, S. A. (1998) A new method for isolating tyrosine kinase substrates used to identify Fish, an SH3 and PX domain-containing protein, and Src substrate. EMBO J., 17, 4346-4357.

Musco, G., Kharrat, A., Stier, G., Fraternali, F., Gibson, T. J., Nilges, M. and Pastore, A. (1997) The solution structure of the first KH domain of FMR1, the protein responsible for the fragile X syndrome. Nature Structure, 4, 712-716.

Thompson, J. D., Gibson, T. J., Plewniak, F. Jeanmougin, F. and Higgins, D. G. (1997) The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res., 25, 4876-4882.