Independently provide assistance through collaborative research and independent research techniques to the Gene Regulation Section of the Laboratory of Pathology, Center for Cancer Research, National Cancer Institute. The primary objective is to provide services and deliverables through performance of work toward the identification of O-GlcNAc-dependent activity responsible for stimulating Topoisomerase I.
Recent experiments have shown over the past few years that human RNA polymerase II initiation and elongation are directly regulated by the addition and removal of the O-GlcNAcylation post-translational modification. Additionally, published and unpublished data indicate that both enzymes involved in the addition (OGT: O-GlcNAc transferase) and removal of the O-GlcNAc (OGA: O-GlcNAc aminidase) from protein substrates are in complexes with the known transcriptional pausing and elongation machinery. It is thus becoming clear that OGT and OGA are regulating transcription and that this discovery defines a novel regulatory space across the genome. The Contractor will provide research support to the Gene Regulation Section under Dr. David Levens, including conduction experiments involving DNA topology and topoisomerases activity during transcription. A collaboration between the Contractor and Dr. Levens research team recently described a role for DNA topoisomerase I in the regulation of paused RNA pol II and found that Topo I activity was stimulated by the phosphorylation of RNA pol II. The Contractor recently determined that OGT activity is required for active Topo I crude nuclear extracts. It remains to be seen what the full complement of signals regulating RNA pol II elongation are, and the Contractors efforts in the Gene Regulation Section as part of this consulting project will be to identify and dissect those regulatory processes.
Nature of the work to be performed
The issues to be addressed include:
Work towards the identification of the O-GlcNAc-dependent activity responsible for stimulating Topoisomerase I.
Ascertain the topoisomerase-dependency of the transcription elongation in his in vitro transcription system and its regulation by O-GlcNAcylation.
Period of Consultation
The consultation period shall be from May 21, 2018 to February 8, 2019.
CERTIFICATIONS, LICENSE, PHYSICAL REQUIREMENTS OR OTHER EXPERTISE REQUIRED.
The contractor must have:
Doctoral degree in Molecular Biology or related discipline
Willing to work with human and animal tissue samples and cell lines
Knowledge of federal privacy laws and human subjects protection statutes
Experience with Microsoft Office Suite (MS Word, Excel, Outlook, PowerPoint).
Strong communication skills, both oral and written.
Excellent organizational and time management skills.
Job Types: Full-time, Contract