This project aims to find novel restriction enzymes that will be useful in many aspects of molecular biology research. One particular focus will be on restriction endonucleases that are able to recognize modified DNA, especially DNA containing 5-methylcytosine and 5- hydroxymethycytosine since such enzymes have many potential applications in epigenetics research. Enzymes recognizing these modified bases are known to occur in bacterial and archaea strains and in the past, many have been found by random biochemical screening. In the proposed project, the discovery of potential new enzymes will use bioinformatics techniques and take advantage of the large number of currently sequenced prokaryotic genomes, both completely sequenced genome and shotgun sequences. The project will identify good candidates and then use biochemical methods to characterize them. In addition to commercializing any useful enzymes that are found from this screen, the information gained about the biochemical function of the restriction enzymes discovered will be invaluable for genome annotation and will have practical implications for researchers working with pathogenic organisms. The latter will result from our efforts to characterize the restriction-modification systems in pathogens and identify those systems which need either to be knocked out or circumvented by prior modification prior to transformation. Thus, the results of this research will have immediate implications for the fields of epigenetics, pathogenesis and genome annotation.

Public Health Relevance

The tools discovered through this project should greatly enhance and lower the cost of epigenetic research. It will also add to our knowledge of the genes encoded by pathogenic organisms and facilitate research into those organisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
1R44GM100560-01
Application #
8251388
Study Section
Special Emphasis Panel (ZRG1-IMST-J (15))
Program Officer
Maas, Stefan
Project Start
2012-03-05
Project End
2012-09-04
Budget Start
2012-03-05
Budget End
2012-09-04
Support Year
1
Fiscal Year
2012
Total Cost
$218,685
Indirect Cost
Name
New England Biolabs, Inc.
Department
Type
DUNS #
066605403
City
Ipswich
State
MA
Country
United States
Zip Code
01938
Krebes, Juliane; Morgan, Richard D; Bunk, Boyke et al. (2014) The complex methylome of the human gastric pathogen Helicobacter pylori. Nucleic Acids Res 42:2415-32