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Analyses of Fundamental Transcription Factors of Giardia lamblia in Response to Host Environments

Principal Investigator: Dr. Aaron A. Best

The mammalian parasite Giardia lamblia is the leading cause of water borne diarrhea in the United States and is a chronic problem in developing countries leading to malnutrition. Giardia is characterized by a two-stage life cycle, with transition from the intestinal trophozoite form to the infectious encysted form triggered by environmental signals within the mammalian host. In addition, Giardia occupies a unique phylogenetic position, being one of the earliest diverging eukaryotes known. Giardia has a transcription mechanism that shows significant differences from transcription systems observed in animals, plants and fungi, raising questions as to how the organism responds to differing environmental signals encountered in the host and potentially offering unique drug targets. Projects in my lab focus on elucidating the mechanism of transcription in Giardia, using techniques from bioinformatics, genetics, molecular biology and biochemistry. It is well established that the transcription factors T ATA-binding protein (TBP) and Transcription Factor IIB (TFIIB) play critical roles in the recruitment of RNA polymerases to promoters in organisms as divergent as Archaea and Eucarya. Analysis of the Giardia genome sequence reveals that Giardia contains a degenerate TBP and does not possess a gene for TFIIB, a surprising result given the conservation of these proteins in other organisms. Rather, Giardia has a homolog to B Related Factor (BRF), a TFIIB paralog critical in RNA polymerase III transcription. We are currently investigating the in vivo DNA binding sites for the basal transcription factors TBP and BRF on a genome-wide scale. These data will provide molecular level information about gene regulation in this important parasite as it responds to changing environments encountered during infection of mammalian hosts. Students in my laboratory participate in all aspects of hypothesis testing, data interpretation,
writing bioinformatics software, and scientific presentations.

Representative Publications:

  • DeJongh M, Formsma K*, Boillot P*, Gould J*, Rycenga M* and Best A. 2007. Toward the automatic generation of genome-scale metabolic models in the SEED. BMC Bioinform. 8:139. (website)
  • Best AA, Morrison HG, McArthur AG, Sogin ML and Olsen GJ. 2004. Evolution of transcription: insights from the genome of Giardia lamblia. Genome Res. 14:1537-1547. (website)
  • Best AA and Olsen GJ. 2001. Similar subunit architecture of archaeal and eukaryal RNA polymerases. FEMS Microbiol Lett 195:85-90. (website)
  • Morrison HG, McArthur AG, Gillin FD, Aley SB, Adam RD, Olsen GJ, Best AA, Cande WZ, Chen F, Cipriano MJ, Davids BJ, Dawson SC, Elmendorf HG, Hehl AB, Holder ME, Huse SM, Kim UU, Lasek-Nesselquist E, Manning G, Nigam A, Nixon JEJ, Palm D, Passamaneck NE, Prabhu A, Reich CI, Reiner DS, Samuelson J, Svard SG and Sogin ML. 2007. Genomic minimalism in the early diverging, intestinal parasite, Giardia lamblia. Submitted.

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