Professor, Biomedical and Chemical Engineering and Sciences
B.A. Wellesley College 1980
Ph.D. State University of New York, Roswell Park Cancer Institute, Buffalo 1987
BIO 4305 Molecular Basis of Human Disease
BIO 4201 Immunology
BIO 4301 Cell Biology
Program Chair, Biological Sciences and Chemistry 2018-present
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, 2014-2016
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
Director, Premedical Programs, Florida Institute of Technology
Chair, Institutional Biosafety Committee
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.
Leonard, A.C., Rao, P., Kadam, R., and Grimwade, J.E. (2019) Changing perspectives on the role of DnaA-ATP in orisome function and timing regulation. Frontiers in Microbiology, in press
Leonard, A. C., and Grimwade, J.E. (2019) Chromosome Replication and Segregation, in Encyclopedia of Microbiology, Fourth Edition. T. Schmidt, ed. Oxford: Elsevior, in press
Grimwade, J.E., and Leonard, A.C. (2019) Blocking the trigger: inhibition of the initiation of bacterial chromosome replication as an antimicrobial strategy. Antibiotics 8:111 doi.org/10.3390/antibiotics8030111
Rao, P., Rozgaja, T.A., Alqahtani, A., Grimwade, J.E., and Leonard, A.C. (2018) Low affinity DnaA-ATP recognition sites in E. coli oriC make non-equivalent and growthrate-dependent contributions to the regulated timing of chromosome replication Frontiers in Microbiology, 9:1673 doi: 10.3389/fmicb.2018.01673
Grimwade, J.E., Rozgaja, T.A., Gupta, R., Dyson, K., Rao, P., and Lenard, A.C. (2018) Origin Recognition is the predominant role for DnaA-ATP in initiation of chromosome replication. Nucleic Acids Research 46:6140-6151 https://doi.org/10.1093/nar/gky457
Leonard, A.C., and Grimwade, J.E. (2018) Regulation of replication origin firing. Reference Module in Life Sciences (LIFE/Elsevier) doi:10.1016/B978-0-12-809633-8.12304-0
Grimwade, J.E. and Leonard, A.C. (2017) Targeting the bacterial orisome in the search for new antibiotics. Frontiers in Microbiology 8: 2352
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.
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
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.