Gregg Whitworth

Education

• Ph.D. University of California San Francisco, Department of Biochemistry and Biophysics, Program in Biological Sciences 2000-2008
• B.A. Grinnell College, Majors in Biology and Philosophy, 1996-2000

Research

I am interested in understanding the ways in which gene expression in eukaryotes can be regulated post-transcriptionally. There are many essential processing steps which eukaryotic mRNA must undergo to become competent for translation, each of which are carried out by large molecular machines. In comparison to our understanding of transcriptional regulation, however, we know relatively little about how these complexes are modulated to affect the timing or diversity of gene expression.

Recently, we found that one such complex, the spliceosome, can be regulated to rapidly alter the splicing efficiency of specific pre-mRNA transcripts, thereby shifting the cellular population of mature, translatable messages in the yeast Saccharomyces cerevisiae. This discovery was made using a custom microarray platform which allowed us to assay the relative splicing efficiency of every intron-containing transcript in the yeast genome. Through a collaborative effort, we have built a database of thousands of microarray-based splicing profiles representing dozens of unique environmental conditions and hundreds of different mutations in mRNA processing factors.

Across a wide range of different environmental contexts we see evidence of rapid, transcript-specific changes in splicing efficiency. The splicing of transcripts can be both up-regulated and down-regulated in response to environmental cues. In some cases large numbers of transcripts are affected, in others only defined subsets. In total, our data reveal that splicing is a remarkably dynamic and flexible mechanism for post-transcriptional gene regulation in yeast.

Teaching

• BIOL-111: Fundamentals of Biology, “Genes, Drugs, and Toxins"
• BIOL-215: Biochemistry of the Cell

Previously taught at Grinnell College:

• BIO-150: Introduction to Biological Inquiry, “Genes, Drugs, and Toxins"
• BIO-251: Molecules, Cells, & Organisms, with Lab
• BIO-345: Advanced Genetics, with Lab
• BIO-370: Advanced Cell Biology, with Lab
• BIO-395: Advanced Special Topic, “Systems Biology"
• BCM-262L: Introduction to Biological Chemistry - Lab

Selected Publications

• Diverse environmental stresses elicit distinct responses at the level of pre-mRNA processing in yeast. Bergkessel, M.*, G.B. Whitworth* and C. Guthrie. (2011) RNA 17: 1461-78.
  
  
• An Introduction to Microarray Data Analysis and Visualization. Gregg B. Whitworth. In John Abelson and Melvin Simon editors: METHODS IN ENZYMOLOGY, Vol. 470, Guide to Yeast Genetics: Functional Genomics, Proteomics, and Other Systems Analysis, Jonathan Weissman, Christine Guthrie and Gerald R. Fink, Burlington: Academic Press, 2010, pp.19-50.
  
  
• A genetic interaction map of RNA-processing factors reveals links between Sem1/Dss1-containing complexes and mRNA export and splicing. Wilmes, G.M., M. Bergkessel, S. Bandyopadhyay, M. Shales, H. Braberg, G. Cagney, S.R. Collins, G.B. Whitworth, T.L. Kress, J.S. Weissman, T. Ideker, C. Guthrie, and N.J. Krogan. (2008) Molecular Cell 32: 735-46.
  
  
• Genome-wide search for yeast RNase P substrates reveals role in maturation of intron-encoded box C/D small nucleolar RNAs. Coughlin, D.J., J.A. Pleiss, S.C. Walker, G.B. Whitworth, D.R. Engelke. (2008) PNAS 34: 12218-23.
  
  
• Rapid, Transcript-Specific Changes in Splicing in Response to Environmental Stress. Pleiss, J.A.*, G.B. Whitworth*, M. Bergkessel and C. Guthrie. (2007) Rapid, Transcript-Specific Changes in Splicing in Response to Environmental Stress. Molecular Cell 27: 928-937.
  
  
• Transcript Specificity in Yeast Pre-mRNA Splicing Revealed by Mutations in Core Spliceosomal Components. Pleiss, J.A., G.B. Whitworth, M. Bergkessel and C. Guthrie. (2007) Transcript Specificity in Yeast Pre-mRNA Splicing Revealed by Mutations in Core Spliceosomal Components. PLoS Biology 5: e90