Susan A. Gerbi George D. Eggleston Professor of Biochemistry, Professor of Biology

Susan A. Gerbi is the George Eggleston Professor of Biochemistry at Brown University. She obtained her Ph.D. with Dr. Joseph Gall at Yale University in 1970, where they developed the method of in situ hybridization for localization of genes on chromosomes. After a two year postdoctoral fellowship at the Max Planck Institute in Tübingen, Germany, she joined the faculty at Brown University. She has two major research projects:

(1) Initiation of DNA Replication – her lab has devised a method to map the start site of DNA replication at the nucleotide level (Bielinsky and Gerbi, Science 1998). Application of this method to yeast (Bielinsky and Gerbi, Molecular Cell 1999) and higher organisms (Bielinsky et al., Current Biology 2001) revealed that DNA synthesis starts directly next to the binding site for the Origin Recognition Complex of six polypeptides. Her research in progress suggests that a steroid hormone receptor may play a direct role for initiation of DNA replication; this may lead to significant understanding of the role of hormones in certain cancers.

(2) Ribosome Structure, Evolution and Biogenesis – studies in the Gerbi lab demonstrated that certain sequences are evolutionarily conserved, even between bacteria and higher organisms, thus pinpointing regions of functional importance in ribosomal RNA (rRNA). Her lab was the first to show that small nucleolar RNA is required for rRNA processing. Their recent investigations (summarized in Gerbi et al., Curr. Opin. Cell Dev. Biol. 2003), opens the possibility for a new class of antibiotics targeted against eukaryotic pathogens.

Dr. Gerbi has received several honors for her research, including the State of Rhode Island Governor's award for Scientific Excellence and election as President of the American Society for Cell Biology.

Dr. Gerbi is also very active in biomedical Ph.D. training. For over 20 years, she has been the Principal Investigator of the NIH training grant in Molecular and Cell Biology and Biochemistry; this interdisciplinary program involves faculty from 9 departments on the Brown campus and affiliated hospitals. Dr. Gerbi has served on NIH study sections reviewing training grants and participated in NIH workshops about training and careers. She was a member of the National Academy of Sciences Committee on a Study of National Needs for Biomedical Research Personnel and has testified about graduate education before both the House and Senate subcommittees on Appropriations. She chaired the FASEB conference on graduate education, was a founding member and served on the steering committee and as chair of the AAMC Graduate Research Education and Training (GREAT) Group, and has published several articles about the biomedical research workforce (e.g., Gerbi et al., Science 2001; Garrison, Gerbi and Kincade, FASEB J 2003).

Brown Affiliations

Research Areas

scholarly work

Borovjagin, A.V. and Gerbi, S.A. (2005) An evolutionary intra-molecular shift in the preferred U3 snoRNA binding site on pre-ribosomal RNA. Nucleic Acids Res. 33: 4995-5005.

Gerbi, S.A. (2005). Mapping origins of DNA replication in eukaryotes. In "Methods in Molecular Biology, Cell Cycle Protocols". Humana Press, vol. 296: pp. 167-180.

Gerbi, S.A. and Borovjagin, A.V. (2004) Pre-ribosomal RNA processing in multicellular organisms. In "The Nucleolus" (ed. M.O.J. Olson), Kluwer Academic/Plenum Publishers, pp. 170-198.

Borovjagin, A.V. and Gerbi, S.A. (2004) Xenopus U3 snoRNA docks on pre-rRNA through a novel base-pairing interaction. RNA 10: 942-953.

Gerbi, S.A., Borovjagin, A.V., Lange, T.S. (2003) The nucleolus: a site of ribonucleoprotein maturation. Curr. Opin. Cell Biol. 15: 318-325.

Gerbi, S.A., Borovjagin, A.V., Odreman, F.E., Lange, T.S. (2003) U4 snRNA nucleolar localization requires the NPHX/15.5-kD protein binding site but not Sm protein or U6 snRNA association. J. Cell Biol. 162: 821-832.

Gerbi, S.A., Strezoska, Z., Waggener, J.M. (2003). Initiation of DNA replication in multicellular eukaryotes. J. Struct. Biol. 140: 17-30.

Gerbi, S.A. and Lange, T.S. (2002). All small nuclear RNAs (snRNAs) of the [U4/U6.U5] tri-snRNP localize to nucleoli; identification of the nucleolar localization element of U6 snRNA. Mol. Biol. Cell 13: 3123-3137.

Urnov, F.D., Liang, C., Blitzblau, H.G., Smith, H.S., Gerbi, S.A. (2002). A DNase I hypersensitivity site flanks an origin of DNA replication and amplification in Sciara. Chromosoma 111: 291-303.

Lunyak, V.V., Ezrokhi, M., Smith, H.S., Gerbi, S.A. (2002). Developmental changes in the Sciara II/9A initiation zone for DNA replication. Mol. Cell. Biol. 22: 8426-8437.

Gerbi, S.A. and Bielinsky, A.-K. (2002). DNA replication and chromatin. Curr. Opin. Genet. Dev. 12: 243-248.

Bielinsky, A.-K. and Gerbi, S.A. (2001). Where it all starts: eukaryotic origins of DNA replication. J. Cell Science 114:643-651.

Borovjagin, A.V. and Gerbi, S.A. (2001). Xenopus U3 snoRNA GAC-Box A' and Box A sequences play distinct functional roles in rRNA processing. Mol. Cell. Biol. 12: 6210-6221.

Gerbi, S.A., Borovjagin, A.V., Ezrokhi, M., Lange T.S. (2001). Ribosome biogenesis: role of small nucleolar RNA in maturation of eukaryotic rRNA. Cold Spring Harbor Symp.. LXVI: 575-590.

Bielinsky A.-K., Blitzblau, H., Beall, E.L., Ezrokhi, M., Smith, H.S., Botchan, M.R., Gerbi, S.A. (2001). Origin recognition complex binding to a metazoan replication origin. Curr. Biol. 11: 1427-1431.

Mok, E.H., Smith, H.S., DiBartolomeis S.M., Kerrebrock, A.W., Rothschild, L.J., Lange, T.S., Gerbi, S.A. (2001). Maintenance of the DNA puff expanded state is independent of active replication and transcription. Chromosoma 110: 186-196.

Lange, T.S. and Gerbi, S.A. (2000). Transient localization of U6 small nuclear RNA in Xenopus laevis oocytes. Mol. Biol. Cell 11: 2419-2428.

Borovjagin, A.V. and Gerbi, S.A. (2000). The spacing between functional cis-elements of U3 snoRNA is critical for rRNA processing. J. Mol. Biol. 300: 57-74.

Lange, T.S., Ezrokhi, M., Amaldi, F., Gerbi, S.A. (1999). Box H and Box ACA are Nucleolar Localization Elements of U17 snoRNAs. Mol. Biol. Cell 10: 3877-3890.

Gerbi, S.A., Bielinsky, A.-K., Liang, C., Lunyak, V.V., Urnov, F.D. (1999). Methods to map origins of replication in eukaryotes. In Eukaryotic DNA Replication: a Practical Approach (ed., S. Cotterill), Oxford University Press, pp. 1-42.

Bielinsky, A.-K. and Gerbi, S.A. (1999). Chromosomal ARSI has a single leading strand start site. Molec. Cell 3: 477-486.

Borovjagin, A.V. and Gerbi, S.A. (1999). U3 small nucleolar RNA is essential for cleavage at sites 1, 2 and 3 in pre-rRNA and determines which rRNA processing pathway is taken in Xenopus oocytes. J. Mol. Biol. 286: 1347-1363.

Lange, T.S., Borovjagin, A. V., Gerbi, S.A. (1998). Nucleolar localization elements in U8 snoRNA differ from sequences required for rRNA processing. RNA 4: 789-800.

Bielinsky, A.-K. and Gerbi, S.A. (1998). Discrete start sites for DNA synthesis in the yeast ARSI origin. Science 279: 95-98.

Lange, T.S., Ezrokhi, M., Borovjagin, A.V., Rivera-León, R., North, M.T., Gerbi, S.A. (1998). Nucleolar localization elements of Xenopus laevis U3 small nucleolar RNA. Mol. Biol. Cell 9: 2973-2985. (including the journal cover)

Lange, T.S., Borovjagin, A., Maxwell, E.S., Gerbi, S.A. (1998). Conserved Boxes C and D are essential nucleolar localization elements of U8 and U14 snoRNAs. EMBO J 17: 3176-3187.

research overview

Tools of molecular biology allow us to analyze the structure, function, and evolution of eukaryotic nucleic acids. Currently, there are two main projects in which we are involved: DNA Replication and Ribosomal RNA.

http://www.brown.edu/Departments/Molecular_Biology/gerbi/gerbirna2012.html

research statement

Tools of molecular biology allow us to analyze the structure, function, and evolution of eukaryotic nucleic acids. Currently, there are two main projects in which we are involved:

DNA REPLICATION. Initiation of DNA synthesis is the major check point in the cell cycle: the cell is committed to divide once the genome has been replicated. Are there specific regions and sequences where DNA synthesis will start? To address this question, we are using the DNA puffs of the giant salivary gland chromosomes of the fly Sciara coprophila. DNA puffs represent sites of intrachromosomal gene amplification and are an excellent model for study of DNA replication. We have mapped the origin of amplification by 2-D gels, by a 3-D gel method we developed, and by PCR analysis. The origin contracts from an 8 Kb zone of initiation at pre-amplification to 1 Kb at amplification stage. The left boundary is the same at both stages. The change in position of the right boundary when the origin contracts to 1Kb correlates with the appearance there of RNA polymerase II. We are exploring further the interplay between regulation of replication and transcription.

How does DNA amplification override the controls that ensure that an origin fires once and only once per cell cycle? To understand the regulation of initiation, we developed Replication Initiation Point (RIP) mapping to identify the start sites of DNA synthesis at the nucleotide level. We have shown that in yeast and in metazoa (Sciara), the site of initiation of replication is directly adjacent to the Origin Recognition Complex (ORC) binding site. Preliminary data suggest that the steroid hormone, ecdysone, induces DNA amplification, providing the first example of hormonal regulation of DNA replication, and may provide a useful paradigm for understanding certain cancers in humans.

RIBOSOMAL RNA. Previously, we determined the first sequence of a multicellular eukaryotic 28S ribosomal RNA (rRNA). We demonstrated that some nucleotide stretches as well as the secondary structure are conserved between the frog Xenopus and the bacterium E. coli, thereby identifying areas of likely functional importance. Our current studies deal with rRNA biogenesis. Specifically, U3 small nucleolar RNA (snoRNA) is localized in the nucleolus, and we have shown by injection of antisense oligonucleotides into Xenopus oocytes that it plays a role in rRNA processing, the mechanism of which we are presently studying. We demonstrated that U3 and other box C/D snoRNAs require the box C/D signature motif for nucleolar localization. We have also identified the Nucleolar Localization Elements (NoLEs) for box H/ACA snoRNAs and for spliceosomal snRNAs.

Once U3 snoRNA has arrived at its nucleolar destination, it influences the order of cleavages to process pre-rRNA, may act as a chaperone to prevent premature pseudoknot formation in 18S rRNA, and is a molecular bridge to draw together the 5' and 3' ends of 18S rRNA in the precursor. U3 snoRNA docks on pre-rRNA by base-pairing interactions that are species specific, and may allow us to design a new class of antibiotics against eukaryotic pathogens.

funded research

NIH-GM 35929 (12/2002-11/2006)
NIH/NIGMS "Gene Amplification: Sciarid DNA Puffs"

NIH 5-T32-GM 07601 (7/1999-6/2010)
NIH/NIGMS "Training in Molecular and Cell Biology and Biochemistry"

NIH NCRR I P20 RR018728-01 (10/2003 – 9/2008)
P.I.: James Padbury (at Women and Infants Hospital; RI)
NIH/NCRR "COBRE for Prenatal Research"

NIH R01 EB 002583-10A1 (9/2004-6/2009)
(P.I.: Rudolf Oldenbourg at the MBL, MA; co-P.I.: Susan Gerbi)
NIH/EB "Development of New Automated Polarized Light Microscope"

NIH GM 61945 (5/2001-4/2005)
NIH/NIGMS "Biogenesis of Eukaryotic Ribosomes"