research

 

Dr. Chris J. Brandl

B.Sc., UWO; PhD., Toronto

Post-doctoral researcher, Harvard Medical School

Professor

Dept. of Biochemistry

Schulich School of Medicine & Dentistry

MBL C210

(519) 679-2111 ext 86857

Fax: (519) 661-3175


cbrandl@uwo.ca

 

Dr. BrandlMechanisms of transcriptional regulation

The ability of cells to activate gene expression in response to changes in the environment is crucial to all cellular processes. Defects in gene expression are a principal cause of human disease most notably cancer. My lab studies the mechanisms of transcriptional regulation using yeast as a model system to facilitate the combination of biochemical, molecular genetic and genetic techniques. Our principal focus is to determine the structure-function relationships and regulation of the SAGA complex that regulates transcription through the modification of chromatin structure.

image of gel

Current studies include:

1.   Determining the role of Tra1p, a 430 kDa component of the complexes that is related to a group of key cellular protein kinases. Interestingly as well as being required for transcriptional regulation Tra1 is required for telomere elongation. .

2.   The mechanism by which the SAGA component protein Ada2 regulates the histone acetyltransferase activity of Gcn5. Of note, Ada2 also has molecular connections with nuclear pore function.

3.   The role of post-translational modification and processing of components of the SAGA complex.
 

Recent Publications

  1. Hoke SM, Irina Mutiu A, Genereaux J, Kvas S, Buck M, Yu M, Gloor GB, Brandl CJ. Mutational analysis of the C-terminal FATC domain of Saccharomyces cerevisiae Tra1. Curr Genet. 2010 Oct;56(5):447-65.
  2. Gloor GB, Tyagi G, Abrassart DM, Kingston AJ, Fernandes AD, Dunn SD, Brandl CJ. Functionally compensating coevolving positions are neither homoplasic nor conserved in clades. Mol Biol Evol. 2010 May;27(5):1181-91.
  3. Stead BE, Sorbara CD, Brandl CJ, Davey MJ. ATP binding and hydrolysis by Mcm2 regulate DNA binding by Mcm complexes. J Mol Biol. 2009 Aug 14;391(2):301-13.
  4. Yousef AF, Brandl CJ, Mymryk JS. Requirements for E1A dependent transcription in the yeast Saccharomyces cerevisiae. BMC Mol Biol. 2009 Apr 17;10:32.
  5. Hoke et al. (2008) A conserved central region of yeast Ada2 regulates the histone acetyltransferase activity of Gcn5 and interacts with phospholipids. J. Mol. Biol. Dec 26;384(4): 743-55.
  6. Hoke et al. (2008) Systematic genetic array analysis links the Saccharomyces cerevisiae. BMC Genetics 9: 46.
  7. Mutiu et al. (2007) Structure/function analysis of the phosphatidylinositol-3-kinase domain of yeast Tra1. Genetics 177: 151-166.
  8. Mutiu, A.I., Hoke, S.M.T., Genereaux, J. Liang, G. and Brandl, C.J. (2007) The role of histone ubiquitylation and deubiquitylation in gene expression as determined by the analysis of an HTB1K123R Saccharomyces cerevisiae strain. Mol. Genet. Gen. 277: 491-506.
  9. Behrsin, C., Bailey, M.L., Bateman, K., Hamilton, K., Wahl, L., Brandl, C.J., Shilton, B.H., and Litchfield, D.W. (2007) Functional mapping of critical residues in Pin1 by unigenic evolution J. Mol. Biol. 265: 1143-1162.
  10. Hoke, S.M.T., Liang, G., Mutiu, A. I., Genereaux, J. and Brandl, C.J. (2007) C-terminal processing of Spt7 occurs in the absence of a functional SAGA complex. BMC Biochem. (submitted).
  11. Mutiu, A.I., Hoke, S.M.T., Genereaux, J., Hannam, C., MacKenzie, K., Jobin-Robitaille, O., Guzzo, J., Andrews, B., Cote, J., Haniford, D.B. and Brandl, C.J. (2007) Structure/function analysis of the phosphatidylinositol-3-kinase domain of yeast Tra1. Genetics. (in press).
  12. Behrsin, C.D., Brandl, C.J., Litchfield, D.W., Shilton, B.H. and Wahl, L.M. (2006) Development of an unbiased statistical method for the analysis of unigenic evolution. BMC Bioinformatics. 7:150.
  13. Mutiu, A.I. and Brandl, C.J. (2005) RNA isolation from yeast using silica matrices. Journal of Biomolecular Techniques 16: 316-317.