Dr. Kristin Baetz

Biography

Highlights of Research Interests

Yeast functional and chemical genomics, chromosome stability, lysine acetyltransferases, transcription factors, cellulosic fermentation, identification of drug mode of action, proteomics

Research Interests

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 and systems biology techniques. The Baetz laboratory is developing and applying high throughput yeast chemical and functional genomic screening along with proteomics to three areas of research interest.

1. Genetic and Molecular Basis of Chromosome Instability

   Funded by: Canadian Cancer Society Research Institute, Ontario Government Early Research Award, NSERC Discovery Award.

   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.

   Presently the laboratory is focusing on the role of the lysine acetyltransferase NuA4 in chromosome stability and are developing new methods for identify its targets.   We are also attempting to decipher the role of the iron responsive transcription factor Aft1 at the kinetochore and the mechanism through which it impacts chromosome transmission fidelity.

2. Chemical genomic approaches to decipher the biological impact of alkylacylglycerophosphocholine second messengers in Alzheimer’s disease.

   Funded by:CIHR Operating Grant and CIHR Training Program in Neurodegenerative Lipidomics.

   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 exploiting  chemical genomic, proteomic and transcriptome approaches to decipher the biological pathways mediating the cellular effects of a series of alkylacylglycerophosphocholine species that have been associated with Alzheimer ’s disease progression.

3. Improvement of industrial yeast strains used in cellulosic fermentation

   Funded by: Cellulosic Biofuels Network, Agriculture and Agri-food Canada Agriculture Bioproducts Innovation Program

   A major hurdle for the economic viability of the cellulosic biofuels industry is the improvement of industrial yeast strains to ferment five carbon sugars, like xylose, which represent up to 50% of the sugars in cellulosic feedstocks. A second hurdle is the development of robust strains which can tolerate the complex inhibitor mixes found in cellulosic biomasses.  The Baetz lab is apply an integrative systems biology approach to tackle both these problems with the aim of developing novel genetic strategies to improve the efficiency of industrial yeast to ferment a variety of cellulosic biomasses.

Are you interested in joining the Baetz Lab for your graduate or postdoctoral training?  Please send your CV to [email protected]

Selected Publications

• Hamza, A., Baetz, K. The iron-responsive transcription factor Aft1 interacts with the kinetochore protein Iml3 and promotes pericentromeric cohesin. J. Biol. Chem. December 2011; jbc.M111.319319.
• Mitchell, L., Lau, A., Lambert, J.P., Fong, Y., Couture, J.F., Figeys, D., Baetz, K. Regulation of septin dynamics by the Saccharomyces cerevisiae lysine acetyltransferase NuA4. PLoS One. 2011;6(10):e25336.
• Usher, J., Balderas-Hernandez, V., Quon, P., Gold, N.D., Martin, V.J.J., Mahadevan, R., Baetz, K. Chemical and synthetic genetic array analysis identifies genes that suppress xylose utilization and fermentation in Saccharomyces cerevisiae. G3:Genes|Genomes|Genetics. September 2011; 1:247-258; doi:10.1534/g3.111.000695.
• Batenchuk, C., St-Pierre, S., Tepliakova, L., Adiga, S., Szuto, A., Kabbani, N., Bell, JC., Baetz, K., Kaern, M. Chromosomal position effects arise from Sir2-mediated variation in transcriptional bursting. Biophysical Journal. May 18 2011;100(10):L56-8.
• Kennedy, M.A., Kabbani, N., Lambert, J-P., Swayne, L.A., Ahmeda, F., Figeys,D., Bennett, S.A.L.,Bryan, J., Baetz, K. Srf1 is a novel regulator of Phospholipase D activity and is essential to buffer the toxic effects of C16:0 Platelet Activating Factor. PLoS Genetics. Feb 10 2011;7(2):e1001299.
• Lambert, J.P., Fillingham, J., Siahbazi, M., Geenblatt, J. Baetz, K., Figeys, D. Defining the Budding Yeast Chromatin Associated Interactome. Molecular Systems Biology. Dec 21, 2010;6:448.
• Berthelet, S., Usher, J., Shulist, K., Hazma, A., Maltez, N., Johnston, A., Fong, Y., Harris, L., Baetz K. Functional genomics analysis of the Saccharomyces cerevisiae iron responsive transcription factor Aft1 reveals iron-independent functions. Genetics. 2010; May 20 ePub ahead of print.
• Lambert, JP., Baetz, K†., Figeys, D.†  Of Proteins and DNA; Proteomic Role in the Field of Chromatin Research. Molecular BioSystems.  2010; 6(1):30-7. † co-corresponding authors.
• Lambert, JP., Mitchell,L., Rudner,A., Baetz, K.†, Figeys, D.† A novel proteomic approach for the development of chromatin associated protein networks. Molecular and Cellular Proteomics. 2009; 8(4):870-82. † co-corresponding authors.
• Mitchell, L., Lambert, J.P, Gerdes M, Al-Madhoun AS, Skerjanc IS, Figeys D, Baetz K.  Functional dissection of the NuA4 histone acetyltransferase reveals its role as a genetic hub and that Eaf1 is essential for complex integrity. Molecular and Cellular Biology. 2008;28(7):2244-2256.
• Baetz K, Kaern M. Predictable trends in protein noise. Nature Genetics. 2006; 38(6):610-611.
• 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;5(6):592-5.
• 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;26(8):3018-28.
• 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;20(6):660-5.
• 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;102(39):13956-61. +Authors contributed equally
• 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;101(37):13513-8. +Authors contributed equally
• 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;101(13):4525-30.
• 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;24(3):1232-44.