Kristin Baetz
Assistant Professor

Degrees:

B.Sc. Queen's University 1995
Ph.D. University of Toronto 2000
Post-doctoral Research University of British Columbia

Research Interests:

Yeast functional and chemical genomics, chromosome stability, identification of drug mode of action.

Research Interest:

During evolution, there has been a high level of conservation between the budding yeast Saccharomyces cerevisae's cellular processes and those of mammalian cells. The advantages of using S. cerevisiae as a model system are multiple, including easy genetic manipulation and availability of several experimental tools for genetic, biochemical and molecular biology studies. Thus, S. cerevisiae has been the platform model organism for the development of genomic techniques and systems biology to analyze their biological functions. The Baetz laboratory is developing and applying high throughput yeast chemical and functional genomic screening to two areas of research interest.

1) Genetic and Molecular Basis of Chromosome Instability

Scientists have found chromosome gain or loss in nearly all major human tumour types. Dr. Baetz's current research project involves developing and implementing yeast chemical and functional genomic screens in order to identify networks of proteins required for chromosome stability in S. cerevisiae . Once the proteins that are required for chromosome stability are identified, she and her research team uses traditional methods drawn from biochemistry and molecular biology to reveal the molecular mechanisms used by these proteins to prevent chromosome loss. Considering the conservation between yeast and human processes governing chromosome segregation, the Baetz laboratory's research with yeast will be of directly relevance to human cancer biology, and will provide new insights into the molecular mechanism of chromosomal instability.

2) Identification of Chemical Mode of Action

Chemicals identified by phenotypic screening are valuable genetic tools to study complex cellular process and are often attractive candidates for drug development. Identification of the mechanism of action or target of these chemicals is critical for evaluating and optimizing therapeutic agents. The Baetz laboratory exploits the cross-species conservation of biochemical pathway function between yeast and human cells to gain insights into the mode of action of various compounds. In particular the laboratory is performing cell-based robotic screening procedures with the yeast deletion mutant arrays to discover drug targets or mode of action.

The Baetz laboratory is supported by the National Cancer Institute of Canada and the Terry Fox Foundation.

Selected Publications:

Baetz K, Kaern M. Predictable trends in protein noise. Nature Genetics. 2006 Jun;38(6):610-611. Abstract / Full paper

Baetz K, Measday V, Andrews B. Revealing hidden relationships among yeast genes involved in chromosome segregation using systematic synthetic lethal and synthetic dosage lethal screens. Cell Cycle. 2006 Mar;5(6):592-5. Abstract / Full Paper

Martin DG, Grimes DE, Baetz K, Howe L. Methylation of histone H3 mediates the association of the NuA3 histone acetyltransferase with chromatin. Molecular and Cellular Biology. 2006 Apr;26(8):3018-28. Abstract / Full Paper

Keogh MC, Mennella TA, Sawa C, Berthelet S, Krogan NJ, Wolek A, Podolny V, Carpenter LR, Greenblatt JF, Baetz K, Buratowski S. The Saccharomyces cerevisiae histone H2A variant Htz1 is acetylated by NuA4. Genes and Development. 2006 Mar 15;20(6):660-5. Abstract / Full Paper

Measday V+, Baetz K+, Guzzo J, Yuen K, Kwok T, Sheikh B, Ding H, Ueta R, Hoac T, Cheng B, Pot I, Tong A, Yamaguchi-Iwai Y, Boone C, Hieter P, Andrews B. Systematic yeast synthetic lethal and synthetic dosage lethal screens identify genes required for chromosome segregation. Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13956-61. +Authors contributed equally Abstract / Full Paper

Krogan NJ+, Baetz K+, Keogh MC+, Datta N, Sawa C, Kwok TC, Thompson NJ, Davey MG, Pootoolal J, Hughes TR, Emili A, Buratowski S, Hieter P, Greenblatt JF. Regulation of chromosome stability by the histone H2A variant Htz1, the Swr1 chromatin remodeling complex, and the histone acetyltransferase NuA4. Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13513-8. +Authors contributed equally Abstract / Full Paper

Baetz K, McHardy L, Gable K, Tarling T, Reberioux D, Bryan J, Andersen RJ, Dunn T, Hieter P, Roberge M. Yeast genome-wide drug-induced haploinsufficiency screen to determine drug mode of action. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4525-30. Abstract / Full Paper

Baetz K, Krogan NJ, Emili A, Greenblatt J, Hieter P. The ctf13-30/CTF13 genomic haploinsufficiency modifier screen identifies the yeast chromatin remodeling complex RSC, which is required for the establishment of sister chromatid cohesion. Molecular and Cellular Biology. 2004 Feb;24(3):1232-44. Abstract / Full Paper

Baetz K , Moffat J, Haynes J, Chang M, Andrews B. Transcriptional coregulation by the cell integrity mitogen-activated protein kinase Slt2 and the cell cycle regulator Swi4. Mol Cell Biol . 2001 Oct;21 (19):6515-28.

Baetz K , Andrews B. Regulation of cell cycle transcription factor Swi4 through auto-inhibition of DNA binding. Mol Cell Biol. 1999 Oct;19(10):6729-41.

Madden K, Sheu YJ, Baetz K , Andrews B, Snyder M. SBF cell cycle regulator as a target of the yeast PKC-MAP kinase pathway. Science. 1997 Mar 21;275(5307):1781-4.