个人简介

B.A. Wellesley College 1980 Ph.D. State University of New York, Roswell Park Cancer Institute, Buffalo 1987 Professor, Department of Biological Sciences, Florida Institute of Technology, 2007-present Research Committee Member, East Central Florida Memory Disorder Clinic, 2009-present Board of Directors, VNA of the Space Coast, 2014-present Associate Professor, Department of Biological Sciences, Florida Institute of Technology, 2000-2007 Assistant Professor, Department of Biological Sciences, Florida Institute of Technology, 1994-2000 Research Scientist, Department of Biological Sciences, Florida Institute of Technology, 1989-1994 NIH Post-Doctoral Fellow, Biology Department, University of Rochester, Rochester, NY 1987-1989

研究领域

My principal research interest focuses on understanding molecular mechanisms that regulate bacterial growth. One ultimate goal of this research is to identify molecular targets that can be used to identify novel antibiotics. My major research project, which is a collaboration with Dr. Alan Leonard, is to characterize nucleoprotein complexes involved in initiation of DNA replication in bacteria.

Some of the questions being studied in our labs are: What proteins bind to the origin of DNA replication? At what time in the cell division cycle to these proteins bind? How is the timing of DNA replication coupled to the growth rate of the cell? How are complexes assembled and disassembled so that replication timing is precisely controlled? In order to answer these questions, we use a combination of biochemical, physiological and genetic techniques. Many of our studies use the extremely well characterized gut bacterium, Escherichia coli. Recently, however, the lab has begun to examine initiation of DNA replication and growth control of other pathogenic bacteria, such as Mycobacteria tuberculosis and Vibrio cholerae. Study of cell cycle control in diverse organisms may reveal fundamental regulatory mechanisms, which will help us understand cell growth in all organisms.

近期论文

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Saxena R., Vasudevan S., Patil D., Ashoura N., Grimwade J.E., and Crooke, E. (2015) Nucleotide-induced conformational changes in Escherichia coli DnaA protein are required for bacterial ORC to Pre-RC conversion at the chromosomal origin. IJMS 16:27897-27911 Leonard, A.C., and Grimwade, J.E. (2015) The orisome: structure and function. Front. Microbiol. 6:545. doi: 10.3389/fmicb.2015.00545 Kaur, G., Vora, M.P., Czerwonka, C.A., Rozgaja, T.A., Grimwade, J.E., and Leonard, A.C. (2014) Building the bacterial orisome: high-affinity DnaA recognition plays a role in setting the conformation of oriC DNA, Mol. Microbiol. 91:1148-1163. Leonard, A.C. and Grimwade, J.E. (2014) Chromosome replication and segregation, Reference Module in Biomedical Research, pp. 1-14, Elsevior. Rozgaja, T, Grimwade, J.E, , Iqbal, M., Czerwonka, C., Vora. M., and Leonard, A.C. (2011) Two oppositely-oriented arrays of low affinity recognition sites in oriC guide progressive binding of DnaA during E. coli pre-RC assembly, Mol. Microbiol., 82:475-488 Saxena, R., Rozgaja, T., Grimwade, J.E., and Crooke, E. (2011) Remodeling of nucleoprotein complexes is independent of a mutant AAA+ protein's nucleotide state, J. Biol. Chem., 286:33770-33777 Leonard, A.C., and Grimwade, J.E. (2011) Regulation of DnaA assembly and activity: taking directions from the genome, Annual Review of Microbiology, 65:19-35 Leonard, A.C., and Grimwade, J.E. (2010) Regulating DnaA complex assembly: it's time to fill the gaps, Curr. Opin. Microbiol., 13:766-772 Leonard, A. C., and Grimwade, J. E. (2010) Chapter 4.4.1, Initiation of DNA Replication. In A. Bck, R. Curtiss III, J. B. Kaper, P. D. Karp, F. C. Neidhardt, T. Nystrm, J. M. Slauch, C. L. Squires, and D. Ussery (ed.), EcoSalEscherichia coli and Salmonella: cellular and molecular biology. http://www.ecosal.org. ASM Press, Washington, DC. Miller, D.T., Grimwade, J. E., Betteridge, T., Rozgaja, T., Torgue, J.JC., and Leonard, A.C. (2009) Bacterial origin recognition complexes direct assembly of higher order DnaA oligomeric structures, Proc. Natl. Acad. Sci. USA, 106:18479-18484 Grimwade, J.E., and Leonard, A.C. (2009) Initiating chromosome replication in E. coli: it makes sense to recycle. Genes & Dev., 23:1145-1150 Leonard, A. C., and Grimwade, J.E. (2009) Chromosome Replication and Segregation, in Encyclopedia of Microbiology, Third Edition. M. Schaechter, ed. pp. 493-506 Oxford: Elsevier Nievera, C., Torgue, J.J.C., Grimwade, J.E., and Leonard, A.C. (2006) SeqA blocking of DnaA-oriC interaction ensures staged assembly of the E. coli pre-RC, Mol. Cell, 24: 581-592. Madiraju, M.V.V.S., Moomey, M., Neuenschwander, P.F., Muniruzzaman, S., Yamamoto, K., Grimwade, J.E. and Rajagopalan, M. (2006) The intrinsic ATPase activity of Mycobacterium tuberculosis DnaA promotes rapid oligomerization of DnaA on oriC. Mol. Microbiol. 59:18761890 Leonard, A.C., and J.E. Grimwade. (2005) Building a bacterial orisome: emergence of new regulatory features for replication origin unwinding. Mol. Microbiol. 55: 978-485. McGarry, K.C., V.T. Ryan, J.E. Grimwade and A.C. Leonard (2004) Two discriminatory binding sites in the Escherichia coli replication origin are required for DNA strand opening by initiator DnaAATP. Proc. Natl., Acad. Sci., USA 101: 2811-2816. Ryan, V.T., J.E. Grimwade, J.E. Camara, E. Crooke and A.C. Leonard (2004) Precise E. coli pre-replication complex assembly is regulated by dynamic interplay between Fis, IHF and DnaA. Mol. Microbiol. 51: 1347-1359.