Department of Microbiology and Immunology

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Ph.D., RockefellerInstitute, 1963






Analysisof regulation of the eukaryotic cell cycle.

The focusof the laboratory is to understand, analyze, and study the regulation ofeukaryotic cell growth and division. The work is carried forward in a numberof directions: 

1.The control of phosphorylation of the retinoblastoma protein is being analyzedunder conditions where the normal division cycle is analyzed and perturbationsof the cell cycle are minimized. We find that contrary to current belief,a phosphorylation-dephosphorylation of the Rb protein is not required duringthe mammalian division cycle.   See Cooper, Yu, and Shayman,IUBMB (1999), and Cooper and Shayman. Cell and Molecular Life Sciences(2001) below.

2.Time lapse videography is being pursued in order to analyze the methodscurrently being used to synchronize cells. Our results indicate that variousstarvation and inhibition methods do not synchronize cells. These resultssupport theoretical analyses of synchronization methods. See Cooper, CellBiology International (2002) below.

3.We are studying the expression of BRCA1 protein during the division cycleand its phosphorylation pattern in order to understand how it is regulatedduring the division cycle. 

4.We are studying the expression of various cyclins during the normal divisioncycle in order to reexamine the current view of cyclin biogenesis and control.We are comparing results from two-color flow cytometric analysis with directbiochemical analysis in order to see whether localization of cyclins canaccount for the observed results.

5. We are reanalyzing publicly available data from Microarray analysis inorder to see whether proposals of G1-phase gene expression are statisticallysignificant.  See Shedden and Cooper, PNAS (2002) and Shedden andCooper, Nucleic Acids Research (2002) below.




Cooper,S. 1979. A unifying model for the G1 period in prokaryotes and eukaryotes.Nature 280:17-19. 

Cooper,S. 1987. G(0) and Cell Cycle Controls. Bioessays 7:220-223. 

Cooper,S. 1997. Division Pattern of a Round Mutant of Escherichia coli.J. Bacteriol. 179:5582-5584

Cooper,S. 1997. DNA Replication: the 30th Anniversary of the Bacterial Modeland the "Baby Machine". TIBS; 22:490-494.

Cooper,S. 1998. On the proposal on a G0 phase and the Restriction Point.FASEB J. 12:367-373.

Cooper,S.1998. On the Interpretation of the Shortening of the G1-phase byOverexpression of Cyclins in Mammalian Cells.    Exp.Cell Res. 238:110-115 .

Cooper,S. 1998. Mammalian Cells are Not Synchronized in G1 Phase by Starvationor Inhibition: Considerations of the Fundamental Concept of G1-phase Synchronization.CellProlif. 31:9-16.

Cooper,S. 1998. Length Extension in Growing Yeast: Is Growth Exponential?Yes.Microbiology. 144:263-266.

Cooper,S. and Keasling, J. D. 1998. Cycle-specific Replication of Chromosomaland F-plasmid Origins.  FEMS Micro. Lett. 163:217-222

CooperS. 1999. The Continuum Model and G1-Control of the Mammalian Cell progress in Cell Cycle Research. Vol. 4. Chapter 3 (L. Meijer,S. Guidet, and M. Philippe, eds.)   Plenum Press, NYC. 27-39.

CooperS., Yu, C. and Shayman, J.A. 1999. Phosphorylation-Dephosphorylationof Retinoblastoma Protein is Not Necessary for Passage Through the MammalianDivision Cycle. IUBMB-Life. 48:225-230.

Cooper,S. 2000. Toward a Standard System for the Mammalian Cycle. ASM News66:71-75(copyrighted by the American Society for Microbiology and reprinted bypermission of ASM News).

Cooper,S., and Shayman, J.A. 2001. Revisiting Retinoblasoma Phosphorylationduring the Mammalian Cell Cycle.     Cellular and MolecularLife Sciences  58:580-595.

Cooper,S 2001.  Revisiting the Relationship of the Mammalian G1Phase to Cell Differentiation.  J. Theor. Biol.  208:399-402.

Cooper,S. 2001 Helical Growth and the Shape of Vibrio Cholerae. FEMS Letters.198:123-124.

Cooper,S. 2001. Size, Volume, Length and the Control of the Bacterial DivisionCycle.  Microbiology.  Microbiology 147: 2629-2630; also page2632.

Shedden,K. and  Cooper, S. 2002.  Analysis of Cell-Cycle-SpecificGene Expression in Human Cells as Determined by MicroarraysProc.Natl. Acad.Sci. USA  99:4379-4384.

Cooper,S. 2002.  Reappraisal of G1-phase arrest and synchronization bylovastatin.  Cell Biol. Int.  27:715-727.

Cooper,S. 2002. Minimally Disturbed, Multi-Cycle, and Reproducible Synchronyusing a Eukaryotic "Baby Machine"    Bioessays.  24:499-501

Cooper,S. 2002. The Schaechter-Bentzon-Maaløe experiment and the analysisof cell cycle events in eukaryotic cells. Trends in Microbiology. 10:169-173.  (reprinted with permission from Elsevier Science.  The Home page of Trends in Microbiology is .  Singlecopies of the article can be downloaded and printed for the reader's personalrsearch and study.

Shedden,K. and Cooper, S. 2002.  Analysis of Cell-Cycle Gene Expressionin S. cerevisiae Using Microarrays and Multiple Synchronization Methods.Nucleic Acids Research.  30: 2920-2929

Cooper,S. 2002.  Cell cycle analysis and microarrays , Trends in Genetics. 18:289-290

Cooper,S. 2002. Cell Biology Moves Forward in 2050. ASM News. 68:260-261.

Cooper,S.  2003.  Rethinking synchronization of mammalian cellsfor cell cycle analysis. Cellular and Molecular Life Sciences 6:1099-1106

Cooper,S. 2003. Reappraisal of Serum Starvation, the Restriction Point, G0,and G1-phase Arrest Points.  FASEB J. 17:333-340

Cooper,S. 2003  How the change from FLM to FACS affected our understandingof the G1 phase of the cell cycle.  Cell Cycle.  2:157-159

Cooper,S. and Shedden, K. 2003. Microarray Analysis of Gene Expression duringthe Cell Cycle.   Cell & Chromosome, 2:1.

Cooper,S. The Continuum Model: Regulation of the mammalian cell cycle is relatedto a continuous accumulation process and not dependent on phase-specificcascades of gene expression. Mathematical Biosciences Institute Workshop,Ohio State University, Columbus, Ohio. September 29-October 3, 2003.

Cooper,S. 2004.  The Ideas of Ludwik Fleck and Their Application to theEukaryotic Cell Cycle, the Restriction Point, and G1-phase Control In Preparation

Cooper,S. and Keasling, J. D. 2004. Experimental and theoretical considerationsof P1-plasmid replication and segregation during the E. coli cell cycle. Journal of Biological Sciences. 5:222-229

Cooper,S. 2004. The Continuum Model of the Eukaryotic Cell Cycle: Applicationto G1-phase control, Rb phosphorylation, Microarray Analysis of Gene Expression,and Cell Synchronization. Clinical Oncology. 26:205-206

The following four articles constitute a debate regarding the efficacy of whole culture synchronization:

Cooper,S. 2004. Is whole-culture synchronization biology's ‘perpetual-motionmachine’?  Trends in Biotechnology 22: 266-269 

PaulT. Spellman, P. T.  and Gavin Sherlock, G.  2004. Reply: whole-culturesynchronization ? effective tools for cell cycle studies  Trends inBiotechnology 22: 270-273 

Cooper, S. 2004 Rejoinder: whole-culture synchronization cannot, and does not,synchronize cells  Trends in Biotechnology 22: 274-276 

Spellman, P. T and Sherlock , G. 2004. Final words: cell age and cell cycle are unlinked Trends in Biotechnology  22: 277-278 

Cooper, S. 2004. Reanalysis of the protocol for in vitro synchronization ofmammalian astrocytic cultures by serum deprivation. Brain Research Protocols. 15:115-118

Cooper, S. 2004. Control of and Maintenance of Mammalian Cell Size  BMC Cell Biology. 5:35

Cooper, S. 2004.  On the persistence of Whole-Culture Synchronizationfor cell-cycle analysis.  in preparation

Cooper, S. 2004.  Bacterial Growth and Division. Article in Encyclopediaof Molecular Cell Biology and Molecular Medicine.  Wiley-VCH. Volume 1.

Cooper, S. 2005 Comment on and reply to “Analysis of variation of amplitudes in cell cycle gene expression” by Liu, Gaido and Wolfinger: On the analysis of gene expression during the normal, eukaryotic, cell cycle Theoretical Biology and Medical Modeling. 2:47

Cooper, S., Iyer, G., Tarquini, M., and Bissett , P. 2006, Nocodazole does not synchronize mammalian cells. Cell and Tissue Research, 324:237-242

Cooper, S. 2006 Distinguishing between linear and exponential cell growth during the division cycle: Single-cell studies, cell-culture studies, and the object of cell-cycle research. Theoretical Biology and Medical Modeling. 3:10

Cooper, S. 2006. Checkpoints and Restriction Points in Bacteria and Eukaryotic Cells. Bioessays. Accepted for publication.

Cooper, S. 2006. Regulation of DNA synthesis in bacteria: Analysis of the Bates/Kleckner licensing/initiation-mass model for cell-cycle control.  Molecular Microbiology, Accepted for publication.  

Cooper, S.  2006.  TheContinuum Manifesto.  Manuscript in Preparation.

Inaddition to these papers, much of this work is analyzed in detail in thebook

Cooper,S. Bacterial Growth and Division, Biochemistry and Regulation of Prokaryoticand Eukaryotic Division Cycles, Academic press. 1991.