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Molecular Genetics and Genomics Program at Wake Forest University School of Medicine

Mark O. Lively
Professor of Biochemistry, and Director of Molecular Genetics Program 

B.S., 1975 Georgia Institute of Technology 
Ph.D., 1978 Georgia Institute of Technology 

 

The primary focus of this laboratory is on the cellular roles and mechanisms of catalysis of novel proteolytic enzymes involved in the processing and secretion of proteins from eukaryotic cells. A major objective is to describe the enzymatic mechanism of microsomal signal peptidase, an endopeptidase of the endoplasmic reticulum that is an essential component of the biosynthetic pathway of most secretory proteins. The first known inhibitors of signal peptidases have been discovered in this lab and are being used to identify the active site amino acid residues of this novel proteinase. Site directed mutagenesis of a signal peptidase substrate produced by bacterial expression is being used to explore the specificity requirements of the enzyme.

Dr. Lively is the director of the Biomolecular Resource Facility at
Wake Forest. This laboratory includes four core laboratory components: the Protein Analysis Core Lab, the DNA Synthesis Core Lab, the DNA Sequence and Gene Analysis Core Lab and the Bioinformatice Resource. The Protein Analysis Core lab provides a proteomics techniques for analysis and identification of proteins. The laboratory performs high sensitivity amino acid sequence analysis of proteins and peptides, chemical synthesis of peptides, quantitative amino acid composition analyses, as well as high performance chromatography methods for purification of peptides and proteins. The DNA Synthesis Core Lab provides custom synthesized deoxy oligonucleotides for investigators at WFU. The DNA Sequence and Gene Analysis Core performs automated DNA sequence analysis using a PE Biosystems Model 377 DNA sequencer for laboratories. Dr. Lively also manages a bioinformatics server that provides software and databases for genetic analysis. The server hosts the Wisconsin Sequence Analysis Software package provided by the Genetics Computer Group, Inc. (GCG) for use by investigators at Wake Forest University


Recent Publications (selected):

Lively MO, and Shelness GS. Eukaryotic Microsomal Signal Peptidases. In: Signal Petidases (Von Heijne, G., Ed.), pp. 59-71, R.G. Landes Publishing Co., Austin, Texas (1994). 

Dalbey RE, Lively, MO, Bron S and van Dijl JM. The chemistry and enzymology of the type I signal peptidases. Protein Science 6:1129-1138 (1997)

Walker SJ and Lively MO: "Signal peptidase (eukaryote)," In: Handbook of Proteolytic Enzymes. (Barrett, A. J., Rawlings, N. D. and Woessner, J. F., eds.) pages 455-460 (1998). 

Lively MO: "Bacterial Type I Signal Peptidases," In: Proteases of Infectious Agents (Dunn, B. M., ed.), Chapter 9, pages 219-229 (1999). 

Lively MO and Ashwell CM: "Signal Peptidases," In: Proteases, New Perspectives (Turk, V. ed.) pages 35-43 (1999). 

Lively MO: "Bioinformatics - Genetic Sites on the World Wide Web," In: Genetics Polymorphisms and Susceptibility to Disease (Miller, M. S. and Cronin, M., eds.) in press, (2000). 

 

Updated 9 March 2000