Print by Debbie Covarrubias
picture of student examining plaque assay
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Puerto Vallarta Beach
Glaunsinger lab-2014

OVERVIEW

The Glaunsinger lab studies the creative strategies viruses use to manipulate gene expression in host cells.  Our primary focus is RNA-based regulation of gene expression, including both transcriptional and posttranscriptional control.  We are interested in viral factors that directly target RNA, as well as how viruses interface with and usurp cellular pathways to control gene expression.  We study these events using gamma-herpesviruses such as Kaposi's sarcoma-associated herpesvirus, which is a major cause of AIDS-associated cancers. We anticipate that these studies will enhance our understanding of virus-host interactions, as well as provide insight into how gene expression pathways are normally regulated in human cells.

Britt Named 2015 HHMI Investigator!!

HHMI celebration
Read about our work, and that of the other new HHMI investigators here: http://www.hhmi.org/news/hhmi-selects-26-nations-top-biomedical-scientists

Research Highlight #1

IFA image of NCL staining
During lytic Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, the viral endonuclease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA). However, select mRNAs escape SOX-induced cleavage and remain robustly expressed. Prominent among these is interleukin-6 (IL-6), a growth factor important for survival of KSHV infected B cells. IL-6 escape is notable because it contains a sequence within its 3’ untranslated region (UTR) that can confer protection when transferred to a SOX-targeted mRNA, and thus overrides the endonuclease targeting mechanism. Postdoc Mandy Muller pursued how this protective RNA element functions to maintain mRNA stability, and identified a set of proteins that associate specifically with the protective element. Remarkably, she found that the IL-6 3’ UTR was also protected against mRNA degradation by the vhs endonuclease encoded by herpes simplex virus, despite the fact that its mechanism of mRNA targeting is distinct from SOX--suggesting that the IL-6 sequence may function as a more broad-acting nuclease escape element. These findings highlight how a network of RNA-protein interactions can impact endonuclease targeting, and identify new features underlying the regulation of the IL-6 mRNA.

Research Highlight #2

graphical abstract
KSHV is a large dsDNA virus that encodes ~89 distinct proteins, most of which are of unknown function or have only predicted activities. Thus, at present we have a vastly incomplete understanding of how this oncogenic virus remodels and co-opts cellular machinery. To systematically identify the set of host proteins hijacked by KSHV, we affinity tagged and purified all 89 KSHV proteins from human cells and analyzed their associated proteins by mass spectrometry (MS) in collaboration with Nevan Krogan's lab. The complete network was assembled from >500 MS runs and refined both computationally and experimentally to yield a final high-confidence interaction map comprised of 564 KSHV-human interactions. This is the largest host-pathogen interactome constructed to date, as well as the first comprehensive protein-protein interaction map for a DNA virus in mammalian cells. Lead author Zoe Davis then used the interactome to study a virus-human hybrid transcription preinitiation complex (PIC) with an essential role in directing viral late gene expression. This PIC incorporates functional mimicry of the human TATA-box-binding protein (TBP) with direct recruitment of cellular RNA polymerase II (Pol II), suggesting a system that merges principles underlying both eukaryotic and prokaryotic transcriptional regulation.

TWiV Comes to Berkeley!

TWiV logo
Vincent Racaniello, the host of the awesome This Week in Virology (TWiV) podcast, visited UC Berkeley! Check out the live podcast at the Microbiology Student Symposium featuring our research~

Lab Location

Li Ka Shing Building photo
Our lab is located in the UC Berkeley Li Ka Shing Center for Biomedical Sciences, on a floor dedicated to infectious disease research. Check out our awesome new space, which includes amazing views of the bay and the beautiful Berkeley campus!
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