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Jeffrey Nickerson, Ph.D.
Academic Role: Associate Professor
Faculty Appointment(s) In:
Cell Biology
Nuclear Architecture and Gene Expression
Nucleic acid metabolism is architecturally organized in the eukaryotic nucleus. Nucleic acids themselves- as well as their metabolism in transcription, RNA processing, and RNA export- are structurally constrained to dynamic nuclear domains. Our larger goal is to understand the mechanisms that accomplish the self-assembly of these domains and achieve the spatial organization of gene expression. Our approach is an interdisciplinary one, combining biochemistry and molecular biology with confocal and electron microscopy.
One ongoing project studies the role of the nuclear matrix protein, SRm160, in RNA splicing and export. SRm160 is recruited to pre-mRNA during spliceosome formation, participates in splicing, and then is retained as part of an Exon Junction Complex (EJC) of proteins bound to the fully processed mRNA. This EJC facilitates the efficient export of mRNA from the nucleus to the cytoplasm. The EJC restructures at the periphery of the nucleus and SRm160 is retained in the nucleus and recycled.
One of our current approaches is to track the movement of EJC complexes and components in the nuclei of live cells by time-lapse confocal microscopy and fluorescence recovery after photobleaching (FRAP). New FRAP techniques we have developed have shown that the intranuclear mobility of the EJC components SRm160 and RNPS1 is ATP dependent, suggesting that their assembly into complexes and movement are regulated. Electron microscopy studies of the SRm160 distribution have shown tracks of the protein between sites of RNA splicing and the nuclear lamina. Our working model, combining these observations is that SRm160-containing complexes may move toward the cytoplasm by a docking-release mechanism regulated by ATP. Stringing binding sites along a track would tend to constrain diffusion to preferred paths within the nucleus.
Other ongoing studies projects study additional protein components of the EJC, study the SRm160-interacting splicing factor SRm300, and measure the binding and mobility of mRNA itself in the nucleus. One collaborative project studies the changes in nuclear and chromatin structure that accompany and facilitate the tissue formation of human breast epithelial cells. We continue to develop new techniques for FRAP experiments and for the analysis of FRAP results.
Office: S7-212 ,LAB /221
Phone: 508-856-2312
E-mail: Jeffrey.Nickerson@umassmed.edu
Keywords:
Cell Biology,
Cell Cycle,
Gene Expression
Postdoctoral Position Available
POSTDOCTORAL POSITION – IMMEDIATE OPENING
Molecular Mechanisms of Breast Tissue Differentiation and Oncogenesis
A position is available immediately to examine the mechanisms controlling breast tissue differentiation, maintenance, and tumorigenesis, with an emphasis on gene regulatory pathways, and higher order chromatin and nuclear structure using an approach intergrating cell and molecular biology. Good verbal and written English skills are required. Send c.v. and contact information for 3 references to:
Jeffrey A. Nickerson, Ph.D. or Anthony N. Imbalzano, Ph.D.,
Department of Cell Biology
UMass Medical School
55 Lake Avenue North
Worcester, MA 01655
Email: anthony.imbalzano@umassmed.edu
or
jeffrey.nickerson@umassmed.edu
POSTDOCTORAL POSITION
A Postdoctoral Position is available immediately in the Department of Cell Biology to study nuclear proteins that participate in RNA processing and export. One of these proteins, SRm160, functions in splicing and then remains bound to the spliced mRNA in the Exon Junction Complex (EJC) that facilitates the export of the mRNA to the cytoplasm. The Postdoctoral Associate would determine the role that SRm160 and its EJC partners play in mRNA export to the cytoplasm. (See: Wagner et al. 2004. J Cell Biology 164:843-850) The experimental approach will integrate molecular and microscopy techniques. Candidates with a strong background in cell biology, biochemistry, or molecular biology are especially desirable.
The University of Massachusetts Medical School is located close to Boston. The Department of Cell Biology has especially strong research programs in nuclear and chromatin structure, cytoskeletal function, and mitotic architecture. The Department supports good core facilities for confocal microscopy, electron microscopy, the development of transgenic mice, and molecular biology.
Interested candidates should contact:
Jeffrey A. Nickerson, Ph.D.
Department of Cell Biology S7-214
University of Massachusetts Medical School
55 Lake Avenue North
Worcester, MA 01655
(508) 856-2312
jeffrey.nickerson@umassmed.edu
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