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Postdoctoral FellowPosted by: University of Idaho
Posted date: Jan-03-2019
Location: Moscow ID
NIH-FUNDED POSTDOCTORAL POSITION IN HOST/PATHOGEN INTERACTIONS
UNIVERSITY OF IDAHO BIOLOGICAL SCIENCES DEPARTMENT
The current project: We hypothesize that HCMV-induced downregulation of two developmentally important genes, nidogen 1 (NID1) at chromosome 1q42 and myelin protein zero (MPZ) at chromosome 1q23, promote cellular conditions likely to foster malfunctions in the CNS and PNS. NID1 is a basement membrane protein secreted by several cell types. NID1 expression is essential for proper brain development. MPZ is the principal PNS nerve sheath protein, expressed exclusively by Schwann cells. Mutations in MPZ are causally linked to late onset SNHL. Expression of both proteins is downregulated in infected tissue culture cells and clinical tissue samples.
We have identified several key elements supporting our hypothesis:
· HCMV’s interactions with the chromosome 1q42 and 1q23 loci are extensive and include 1) binding of the viral tegument protein pp71 to both loci, 2) recruitment and binding of cellular CTCF to both loci, 3) interactions robust enough to break the cellular DNA at both loci, 4) induced degradation of nascent expressed protein (NID1), and 5) downregulation of transcription of one gene (NID1 and MPZ) in close proximity to each locus.
· Expression of pp71 alone decreases NID1 steady state protein levels, inhibits NID1 transcription, and causes both 1q DNA breaks. A second viral protein, UL35, also regulates NID1 steady state levels and causes both breaks. Thus, HCMV actively eliminates NID1.
· Infection and expression of pp71 alone also decreases steady state MPZ protein levels and inhibits its transcription in Schwann cells. Sequence similarity shared by these loci may promote off-target binding of pp71.
· Our work in iPSC-derived cerebral organoids and primary Schwann cells provide clinically relevant and unique model tissue culture systems to support our hypothesis.
We seek to determine 1) how HCMV regulates NID1, 2) the benefit HCMV derives from NID1 downregulation, 3) how HCMV regulates MPZ and 4) the ramifications of NID and MPZ downregulation. In particular, whether MPZ downregulation can induce late onset SNHL.
Your qualifications: Applicants must have a Ph.D. in molecular/cellular biology, virology or a related field and a strong publication record in peer-reviewed English language journals. They must have extensive practical experience with standard molecular/cellular biological techniques and performance of tissue culture driven experiments. Experience in stem and neural cell culture, advanced molecular techniques (ChIPs, qPCR, quantitative realtime RT-PCR, CRISPR-driven experiments) and/or protein/DNA interaction studies, is highly desirable.
The surroundings: There’s a reason that U of I was chosen as one of Outside Magazine’s top universities for outdoor recreation! Northern Idaho is a fabulous place for anyone interested in the outdoors; hiking, fishing, rock climbing, mountain biking, skiing, white water rafting, etc. are all close by. The Palouse is a beautiful place and Moscow is a great small college town!
If interested, send a cover letter and a CV including contact information for 3 references to: Dr. Elizabeth (Lee) Fortunato, University of Idaho Biological Sciences Department, at the email address: lfortuidaho.edu