First Look At A Pilot Project To Determine Feasibility Of Structural Genomics

Structural genomics is touted by many to be the next big thing - one of the next important phases of genomic analysis, after sequencing of many genomes (including that of our own species) is complete.

The sequencing of the human genome is important and impressive, but it will not be sufficient for the development of effective disease therapies because genes are the storehouses of genetic information in cells, not the active participants in cellular processes. Genes encode the blueprints for making proteins, which are the molecules that perform most of the functions in living organisms. Therefore, it is important to determine the function of each protein in an organism, and how it goes about performing its assigned tasks. And, to understand a protein's role in detail, it is necessary to know its structure at atomic resolution.

A major goal of the field of structural genomics is to make the process of protein structure determination automated and extremely rapid (from ~1 year per structure currently to ~1 month or less, for example), so that we can begin to amass atomic resolution structures of all proteins. Another goal is to decrease the cost of each structure determination (from ~$200,000 currently to hopefully ~$20,000) so that the enterprise is financially feasible.

Later this year, the National Institute of General Medical Sciences of the National Institutes of Health in the USA plans to fund several large centers devoted to structural genomics. In the USA and Canada, several pilot projects have been underway to determine the feasibility of high-throughput structure determination. Several are attempting to answer the question: can we expect to determine the structure of every protein in an organism, even one with a small genome such as a bacterium?

Now, in the October issue of Nature Structural Biology (Vol. 7, No. 10, October 2000), Cheryl Arrowsmith and Aled Edwards, of the University of Toronto, and their colleagues give us one of the first looks at the results from one of these pilot projects. They report the progress of their group in analyzing 424 nonmembrane proteins from Methanobacterium thermoautotrophicum The primary goals of their research were to evaluate the technical hurdles involved in such a high-throughput structure determination project, to estimate the percentage of proteins encoded by a genome that are immediately amenable to structural analysis, and to assess the extent to which function can be inferred from the structure of a protein.

Their work indicates that structural genomics is a technically feasible concept but also highlights that there are hurdles to be overcome. For example, they note that the rate of structure determinations for this project was limited by access to expensive instrumentation, such as NMR spectrometers and the synchrotron radiation sources that produce the intense X-ray beams needed to analyze proteins by X-ray crystallography. Therefore, they propose that this is one of the major issues that should be addressed in the pending large scale, internationally coordinated structural genomics projects.

Contact:

Dr. Aled Edwards
University of Toronto
Banting & Best Dept. of Medical Research & Dept. of Med. Biophysics
Charles H. Best Institute
112 College Street
Toronto, Ontario, M5G 1L6
Canada
Tel: 416-946-3436; 416-919-5504
Fax: 416 978-8528 general
Email: aled.edwards@utoronto.ca

Dr. Cheryl Arrowsmith
Ontario Cancer Institute
Dept. of Medical Biophysics/ Div. of Mol. & Structural Biology
University of Toronto
610 University Ave.
Room 7-714
Toronto, Ontario, M5G 2M9
Canada
Tel: 416 946 2017
Fax: 416 946-6529
Email: carrow@oci.utoronto.ca

(C) Nature Structural Biology press release.

Message posted by: Trevor M. D'Souza