Smith, M. Mitchell
Professor, Microbiology, Immunology, and Cancer Biology
- BA, Biology, Johns Hopkins University, Baltimore MD
- PhD, Biochemistry, Johns Hopkins University, Baltimore MD
- Postdoc, Molecular Biology, Johns Hopkins University, Baltimore MD
- Postdoc, Molecular Genetics, Edinburgh University, Edinburgh, Scotland, UK
Functional Genomics of Histones, Chromatin, and Protein Acetylation Signaling in Cancer and the Cell Cycle
My laboratory is interested in the molecular genetics of eukaryotic chromosome structure and function, including the mechanisms of gene transcription, DNA replication, recombination, and chromosome segregation. Our research focuses on the genes that encode the histone proteins which comprise the protein subunits of the nucleosome, the primary building block of the eukaryotic chromosome. Thus, the histones are critical for chromosome structure and dynamics, and their function is required at key steps in the cell division cycle. Our experiments exploit the advanced molecular genetics of the simple eukaryote Saccharomyces cerevisiae, budding yeast. Yeast provides an experimental system that is advantageous for cell biology, biochemistry, and molecular genetic studies. A powerful collection of classical genetic and molecular techniques have been developed for yeast that permit the recombinant DNA cloning and manipulation of genes in vitro and the characterization of new mutants in vivo. Currently, we are focusing on four main research questions:
The roles of the histone amino-terminal tail domains in chromatin structure and function, particularly in DNA replication and the maintenance of genome integrity.
The roles of the nucleosome in regulating gene transcription, and how histone-histone interactions function in shaping the chromatin template.
The roles of the histones in determining the structure and morphogenesis of the centromere of the chromosome.
The roles of the "SNF/SWI" complex in remodeling chromatin for transcription, and its interaction with the adenovirus E1A oncoprotein.