Faculty Member Position Available
Center for RNA Biology
Posted on: 8/7/12
The Center for RNA Biology, directed by Lynne E. Maquat, Ph.D., and co-directed by David H. Mathews, M.D., Ph.D., is soliciting applications from outstanding individuals holding a PhD and/or an MD degree(s) and at least two years of post-doctoral training for a position at the ASSISTANT, ASSOCIATE or FULL PROFESSOR level. Emphasis is being placed on wet-bench and/or computational studies having disease relevance, including but not limited to the study of RNA metabolism or the use of RNA as a therapeutic tool or target. Successful applicants are expected to develop independent, externally funded research programs and to contribute toward graduate- and medical-school teaching. The University of Rochester Medical Center and the adjacent undergraduate College of Arts & Sciences offer an outstanding research environment with established strengths in RNA Biology and excellent opportunities to collaborate with basic scientists and clinicians.
Post-Doctoral Fellow Positions Available
Mechanism of Bacterial and Eukaryotic Translation
Ermolenko Lab (Mechanism of Protein Synthesis)
Posted on: 8/16/11
We are seeking talented and motivated postdoctoral fellow to study mechanism of bacterial and eukaryotic translation. We use ensemble and single molecule fluorescence resonance energy transfer to study structural dynamics of the ribosome and translation factors. Applicants must have a recent Ph.D. and expertise in molecular biology with publications in international peer-reviewed journals. Applicants with experience in ribosome and RNA biochemistry and/or fluorescent spectroscopy are encouraged to apply
Please submit a statement of research interests and experience, and current curriculum vitae to Dr. Ermolenko.
Molecular Virology, DNA Mutagenesis and RNA Editing
Smith Lab (Messenger RNA Expression & Processing)
Posted on: 8/5/11
A funded postdoctoral position is available at the junior or senior level to study the role of cellular defense systems such as APOBEC3G and Activation Induced Deaminase in suppressing viral infectivity, regulating immune response and/or contributing to genomic mutagenic activity. Candidates are being sought who are technically skilled, creative and highly motivated.
The candidate will have the opportunity to further their career training in a highly supportive environment consisting of an interdisciplinary team of investigators with expertise in virology, biochemistry, molecular biology and structural biology and state-of-the-art laboratories and core facilities in the lab and the Biochemistry Ph.D. program at the University of Rochester, Rochester, NY.
Prior graduate or postdoctoral training virology, molecular biology are desirable and/or high throughput assay development are desirable.
Interested applicants should send an application package via email to Prof. Smith. The application package should contain:
- Cover letter
- Full CV
- List of three references
Functional Genomics Screen of Glycosyltransferase
Hagen Lab (Comprehensive Functional Genomics Screen of Glycosyltransferases)
Posted on: 3/28/11
Our lab is recruiting Post-doctoral fellows for work on current research projects. Our research projects provide opportunities for extensive training in the areas of molecular biology, glycobiology, recombinant protein expression, protein purification, biochemical characterization of enzymes, transgenic techniques, microscopy, loss of function reverse genetic screens. Postdoctoral fellows should have training in C. elegans or Drosophila development or have a strong background in molecular biology, glycobiology or proteomics research.
For more information or to apply please contact Dr. Hagen.
Mechanism by Which Termination (Nonsense) Codons Elicit mRNA Decay
Maquat Lab (Normal & Disease-Associated RNA Decay)
Posted on: 1/20/11
Nonsense codons, caused by either frameshift or nonsense mutations, are responsible for an estimated one-third of inherited genetic diseases. We are particularly interested in understanding the changes in mRNP structure that occur during the pioneer round of translation and how the pioneer translation initiation complex is remodeled to the steady-state translation initiation complex.
NMD is a splicing-dependent and translation-dependent pathway that targets not only disease-associated but also naturally occurring transcripts (for recent review, see Maquat et al., 2010, Cell 142:368-74). Many of the naturally occurring transcripts are mistakes made during alternative splicing (Pan et al., 2006, Genes & Dev. 20:153-8). Currently, we are interested in further characterizing the pioneer round of translation, during which nonsense codon recognition leads to NMD (Ishigaki et al., 2001 Cell 106:607-617; Lejeune et al., 2002, EMBO J. 21:3536-3545; Woeller et al., 2008, EMBO Rep. 9:446-451). We have made important progress in identifying components of the pioneer translation initiation complex, which consists of the mostly nuclear but shuttling cap-binding proteins CBP80 and CBP20 at the mRNA cap, poly(A) binding proteins PABPN1 and PABPC1 at the mRNA poly(A) tail, and the exon junction complex (EJC) of proteins that includes the NMD factors UPF3 or UPF3X, UPF2, and, finally, UPF1 (Chiu et al., 2004, Genes & Dev. 18:645-754; Lejeune et al., 2004, Nat. Struct. Mol. Biol. 11:992-1000; Hosoda et al., 2006, Mol. Cell. Biol. 26:3085-3097). We have found that CBP80 promotes NMD by promoting the interaction between UPF1 and UPF2 (Hosoda et al., 2005, Nat. Struct. Mol. Biol. 12:893-901). More recent data indicate that CBP80 escorts UPF1 and its kinase SMG1 to join the translation termination complex eRF1-eRF3 at a premature termination codon and subsequently to join a downstream EJC (Hwang et al., 2010, Mol Cell 39:396-409). Joining results in UPF1 phosphorylation and, as a consequence, translational repression: phospho-UPF1 binds eIF3 of the 43S translation initiation complex that is poised at the initiation codon of an NMD target so as to inhibit 60S ribosomal subunit joining and, thus, formation of a translationally active 80S ribosome (Isken et al., 2008, 133:314-327). We have found that the pioneer round of translation promotes some but not all steps of mRNP remodeling to form the steady-state translation initiation complex. For example, the pioneer round of translation promotes EJC removal and the replacement of PABPN1 by PABPC1 but, remarkably, not the replacement of CBP80-CBP20 by eIF4E. Instead, the karyopherin importin-β mediates the replacement of cap-bound CBP80-CBP20 by eIF4E by interacting with importin-β, which is a stable constituent of cap-bound CBP80-CBP20 (Sato and Maquat, 2009, Gene & Dev. 23:2537-2550). Opportunities are available to research the degradative enzymology of NMD (Lejeune et al., 2003, Mol. Cell 12:675-687), factor function in NMD (Chiu et al., 2003, RNA 9:77-87; Brumbaugh et al., 2004, Mol. Cell 14:585-598; Matsuda et al., 2007, Nat. Struct. Mol. Biol. 14:974-979) and, in collaboration with Rob Singer (Albert Einstein College of Medicine), the spatial difference in cells between nucleus-associated and cytoplasmic NMD (Sato et al., 2008, Mol Cell 29:255-262).
Opportunities are also available to study a related mRNA decay pathway that we have named Staufen1(STAU1)-mediated mRNA decay (SMD) (Kim et al., 2005, Cell 120:195-208; Kim et al., 2007, EMBO J. 26:2670-2681). We have found that STAU1, which is a double-stranded RNA binding protein, recruits the NMD factor UPF1 to certain mRNA 3’-untranslated regions (3’UTRs) so as to elicit SMD in a translation-dependent fashion. Using microarray analyses, we have identified a number of mRNAs that are naturally down-regulated by SMD. Unlike NMD, SMD targets not only CBP80-CBP20-bound mRNA but also its remodeled product, eIF4E-bound mRNA. This makes sense for a conditionally regulated pathway. Remarkably, NMD and SMD are competitive pathways since UPF1 can bind either the UPF2 NMD factor or the STAU1 SMD factor but not both factors simultaneously; competition contributes to myogenesis and probably many other cellular processes (Gong et al., 20090 Genes & Dev. 23: 54-66). We are very excited about our finding that STAU1-binding sites (SBS) can be formed not only by intramolecular base-pairing in an mRNA 3’ UTR but also by intermolecular base-pairing between the Alu element of an mRNA 3’UTR and a partially complementary Alu element in one or more Alu element-containing long noncoding (lnc)RNAs (Gong and Maquat, 2011, Nature, in press). These lncRNAs are cytoplasmic and polyadenylated, and we refer to them as 1/2-sbsRNAs. Thus, we have defined unexpected roles for Alu elements and lncRNAs. Future studies aim to elucidate how mammalian cells utilize SMD to regulate gene expression. Included in these studies is identifying those dsRNA sequences in mRNAs that bind STAU1, defining STAU1-containing mRNA binding complexes, and characterizing the physiological significance of SMD. Additionally, we have evidence that STAU1 can affect mRNA metabolism independently of translation, and we are pursuing studies of this pathway.
Successful candidates will join a well-equipped group of interactive lab members with diverse backgrounds and broad expertise in newly remodeled labs. The University of Rochester is unique for its sizeable community of RNA researchers, its Center for RNA Biology: From Genome to Medicine, and its RNA Structure and Function Cluster, all of which include members of the Medical Center, in which the Maquat lab resides, as well as the College of Arts and Sciences across the street.
Interested individuals should send a C.V., including a description of past and on-going research, and the names and contact information of three references to Dr. Maquat
Mechanism and Regulation of DNA Replication and Repair
Bambara Lab (Human Genome Stability, DNA Damage Response, HIV Replication & Evolution)
Posted on: 1/1/10
An important area of investigation relating to both aging and cancer is the study of mechansims by which mammalian cells coordinate DNA replication and repair, so that damage is repaired before it is passed on to progeny. We are reconstituting the reactions of mammalian Okazaki fragment processing and base excision repair. We recently found that replication protein A greatly stimulates base excision repair and hypothesize that it serves a factor that coordinates the actions of the proteins involved. We are trying to determine the complex function of this protein. The Dna2 protein is both a helicase and nuclease. It is essential for DNA replication but what it does is still unknown. Its biochemical properties are similar to those of FEN1, yet FEN1 cannot be its substitute. We are trying to understand the nature of its essential contribution. The signaling protein p21cip1 is thought to mediate a shift from DNA replication to repair during chromosomal damage. It might do so by binding PCNA. Yet PCNA is involved in both processes. We are trying to determine the mechanism of regulation by p21cip1. The project involves training in protein expression, reconstitution of replication and repair pathways, structural analysis and mutagenesis of proteins, cell culture, and mechanisms of catalysis, regulation and signaling.
Recombination in HIV. The two chromosomes in HIV frequently recombine during replication, a process that evolves viral fitness in a highly undesirable manner. We found that recombination is so efficient because the two chromosomes bind to each other. This binding is most favorable at hairpins, and is stabilized by a process called kissing. The geometry of the loops on some hairpins particularly favor the kissing interaction. The interaction has the ability to propagate along the genome stabilizing many binding sites. The DNA strand being copied from one genome transfers to the other at these sites. We are using genetic modification of the sequence and structure of the RNA to probe the recombination mechanism both in vitro and in vivo. Results will give us a lot of information about RNA-RNA interaction, the mechanism of recombination and the unique evolution of HIV. The project involves reconstitution of recombination in vitro, measurement of RNA-RNA folding and interaction, studies of reverse transcriptase reaction mechanisms and cell culture.
Applicants should send three letters of recommendation to Dr. Bambara and be prepared to speak on their thesis work.
Openings are anticipated in summer 2012
The University of Rochester is an equal opportunity/affirmative action employer.