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 described below. Dr. Gerbi has received several honors for her research, including the State of Rhode Island Governor's award for Scientific Excellence, election as President of the American Society for Cell Biology (ASCB), and election as a Fellow of the American Association for the Advancement of Science (AAAS).
(1) Initiation of DNA Replication:
The Gerbi lab has devised the Replication Initiation Point (RIP) method to map the start site of DNA replication at the nucleotide level (Bielinsky and Gerbi, Science). Application of this method to yeast (Bielinsky and Gerbi, Molecular Cell) and higher organisms (Bielinsky et al., Current Biology) revealed that DNA synthesis starts directly next to the binding site for the Origin Recognition Complex of six polypeptides. Her lab developed the use of λ-exonuclease (λ-exo) to enrich replicating DNA, and this method is now widely used by many groups. λ-exo is the basis for the popular protocol of nascent strand sequencing (NS-seq) to discover and map origins genome-wide, as recently published by the Gerbi lab with suggested refinements.
Dr. Gerbi studies re-replication whereby an origin is activated more than once in a single S phase thereby overriding the normal cellular controls against this. Her studies focus on developmentally regulated control of site-specific re-replication in Sciara DNA puffs, resulting in DNA amplification. Having studied Sciara DNA puff II/9A in depth, she is now extending her experiments to the other 9 major and 9 minor DNA puffs by sequencing the genome of Sciara using cutting edge technology (including the Oxford Nanopore MinION) to identify the other DNA puffs by their increased copy number. The data suggest that the receptor for the steroid hormone ecdysone binds adjacent to ORC and may interact with the replication machinery to promote re-replication. She is investigating if the mechanism used for DNA amplification in Sciara DNA puffs employing a steroid hormone receptor also applies to amplification of genes in human breast cancer, thus elucidating what events initiate DNA amplification that is a hallmark of cancer. Her group has developed methodology for transformation in Sciara allowing mutagenesis to test the importance of candidate cis-regulatory elements such as the ecdysone receptor binding site.
(2) Ribosome Structure, Evolution and Biogenesis:
Ribosomal RNA (rRNA) Structure - The Gerbi lab sequenced the first metazoan 28S rRNA. She showed that certain sequences are highly conserved, even between bacterial and eukaryotic rRNA, thus defining functionally important sites of rRNA. Furthermore, she demonstrated that a core conserved secondary structure exists in rRNA from bacteria through eukaryotes. She discovered inserted sequences that are variable in length and sequence in eukaryotic rRNA that she named “expansion segments”, and these have proven useful for phylogenetic analysis and are the focus of several recent cryo-EM and x-ray crystollography studies by other groups. Her recent bioinformatic analysis of rRNA sequences from all domains of life has identified domain-specific sequence signatures (e.g., conserved nucleotide elements in eukaryotes but not in bacteria or archaea). Her recent investigations opens the possibility for a new class of antibiotics targeted against conserved nucleotide elements.
Ribosomal RNA (rRNA) Processing - The Gerbi lab has elucidated the biogenesis of ribosomes, being the first to show a role in vivo for any small nucleolar RNA (snoRNA). For this, she developed methodology for injection into Xenopus oocyte nuclei of an antisense oligo to disrupt the endogenous U3 snoRNA followed by rescue with a mutated U3 snoRNA to investigate in vivo the mechanism underlying the role of U3 snoRNA for Xenopus rRNA processing. U3 snoRNA seems to act as a chaperone to fold the precursor rRNA and guide sites of cleavage. Her studies on Xenopus rRNA processing have several features that are distinct from rRNA processing in yeast and provide a foundation for current studies by other groups on rRNA processing in humans.
Nuclear Localization of Small RNAs - Susan Gerbi’s group developed methodology to allow in vivo studies on localization of small RNAs in nuclei. The technique involves injection into Xenopus oocytes of a fluorescently tagged small RNA to follow its nuclear localization by fluorescence microscopy. With this approach, she showed that conserved boxes C/D or boxes H/ACA are the nucleolar localization elements (NoLEs) in snoRNAs. She also showed that snRNAs of the spliceosome traffic through the nucleolus. Her lab identified NoLEs for U4 and U6 snRNAs and the elements needed for Cajal body localization.
(3) Graduate and Postdoctoral Training:
Dr. Gerbi has much past experience in mentoring graduate students, postdocs and faculty. She has trained 13 predocs through the PhD and 37 postdocs; both groups have gone on to fulfilling careers in science. She has served as the Principal Investigator (PI) on Brown University’s NIH predoctoral training grant (NIH-5T32-GM07601) in molecular and cell biology from 1982-2010 (33 years) and as co-PI since then. Her success in mentoring has been recognized by two awards from Brown University: (a) Dean’s award for the advancement of women faculty (2009), (b) Dean’s award for excellence in graduate and/or postdoctoral mentoring (2012).
Dr. Gerbi has also played a leadership role at the national level in best practices for graduate student and postdoctoral training, including mentoring: (a) Chair of FASEB Consensus Conference on Graduate Education, (b) Founding member and Chair of the AAMC Graduate Research Education and Training (GREAT) Group. 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. In addition, she was a member of the National Academy of Sciences committee on Bridges to Independence to facilitate the transition from postdoctoral to faculty member, and this led to the NIH K99 award program. Dr. Gerbi has published several papers together with Dr. Howard Garrison of FASEB on predoctoral and postdoctoral training and about the biomedical research workforce.