10

IclR transcription factor family


at the University of Toronto

Alexei Savchenko - short biography

Transcriptional regulation. My Ph. D. thesis was devoted to the characterization of thegene expression regulation mechanism in thermophilic bacteria. Very little was known at that point on this subject and my project was awarded a fellowship from French Ministère des Affaires Etrangères. During my studies, I constructed gene library of thermophilic bacteria Bacillus stearothermophilus in E. coli, that became a powerful and unique source (the genome information for this bacteria became available only recently) for gene identification in several laboratories.

Protein stability mechanisms. Being interested in the mechanisms of protein stability, I commenced my Postdoctoral studies with Dr. Gregory Zeikus at Michigan State University. The goal of my research was to investigate the thermostability mechanisms and potential industrial applications of the enzymes from archaeal and bacterial hyperthermophiles, such as alpha-amylase and amylopullulanase, used in starch processing, and alkaline phosphatase, used in diagnostics. I characterized for the first time the alpha-amylase and amylopullulanase from Pyrococcus furiosus and alkaline phosphatase from Thermotoga neapolitana. I was able to identify thermostability-related structural features of alpha amylase and unique metal ion content of this protein.

Structural proteomics. By the end of my postdoctoral studies I became interested in emerging field of structural proteomics and joined a pilot project in this field with Drs. Aled Edwards and Cheryl Arrowsmith at the University of Toronto. The focus of my studies was to develop high-throughput methodologies for unknown protein characterization using structural and functional approaches. Our success with the genome of archaea Methanobacterium thermoautotrophicum, permitted us (and other structural proteomics groups world wide) to apply developed methodology to both eu- and prokaryotic genomes.

From December 2000 I am supervising a team of researchers at the newly created Ontario Centre for Structural Proteomics in Toronto, which concentrated on structural and functional studies of structurally uncharacterized protein families in microbial genomes. During this period I established a solid framework for this project, which includes the creation of recombinant protein expression libraries and the definition of a unified procedure for high throughput protein purification and structural/functional screens. These two achievements have enabled us to determine over 60 unique structures of representatives of previously structurally non-annotated protein families in collaboration with large network of X-ray crystallography laboratories around the world (will need to create a link to the list of collaborators).

Among these structures are those of protein families of high biomedical relevance such as spermidine synthase and survival protein E, which were determined for the first time by my team.

e-mail: alexei.savchenko@utoronto.ca
phone: 416-946-0082

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