January 2023

Jason McLellan

McLellan Receives 2 Prestigious Awards in Recognition of His Vaccine Work

January 30, 2023

LCID Faculty Member Dr. Jason S. McLellan has been named the 2023 recipient for both the Welch Foundation’s Norman Hackerman Award in Chemical Research as well as the National Academy of Sciences Award in Molecular Biology. The two awards were given in recognition of McLellan’s work as a pioneer in structure-based vaccine design. His work has been instrumental in the development of COVID-19 mRNA vaccines in addition to on-going research towards an effective RSV (Respiratory Syncytial Virus) vaccine that has gone through a successful phase three trial.

The Norman

Read more about McLellan Receives 2 Prestigious Awards in Recognition of His Vaccine Work
Sylvain Blois, Benjamin M Goetz, James J Bull, and Christopher S Sullivan. “Interpreting and de-noising genetically engineered barcodes in a DNA virus.” PLoS Computational Biology, 18, 11, Pp. e1010131. Publisher's Version Abstract
The concept of a nucleic acid barcode applied to pathogen genomes is easy to grasp and the many possible uses are straightforward. But implementation may not be easy, especially when growing through multiple generations or assaying the pathogen long-term. The potential problems include: the barcode might alter fitness, the barcode may accumulate mutations, and construction of the marked pathogens may result in unintended barcodes that are not as designed. Here, we generate approximately 5,000 randomized barcodes in the genome of the prototypic small DNA virus murine polyomavirus. We describe the challenges faced with interpreting the barcode sequences obtained from the library. Our Illumina NextSeq sequencing recalled much greater variation in barcode sequencing reads than the expected 5,000 barcodes-necessarily stemming from the Illumina library processing and sequencing error. Using data from defined control virus genomes cloned into plasmid backbones we develop a vetted post-sequencing method to cluster the erroneous reads around the true virus genome barcodes. These findings may foreshadow problems with randomized barcodes in other microbial systems and provide a useful approach for future work utilizing nucleic acid barcoded pathogens.
Rong Yang, Eunice E Lee, Jiwoong Kim, Joon H Choi, Elysha Kolitz, Yating Chen, Clair Crewe, Nicholas JH Salisbury, Philipp E Scherer, Clay Cockerell, Taylor R Smith, Leslie Rosen, Louisa Verlinden, Denise A Galloway, Christopher B Buck, Mariet C Feltkamp, Christopher S Sullivan, and Richard C Wang. “Characterization of ALTO-encoding circular RNAs expressed by Merkel cell polyomavirus and trichodysplasia spinulosa polyomavirus.” PLoS Pathogens, 17, 5, Pp. e1009582. Publisher's Version Abstract
Circular RNAs (circRNAs) are a conserved class of RNAs with diverse functions, including serving as messenger RNAs that are translated into peptides. Here we describe circular RNAs generated by human polyomaviruses (HPyVs), some of which encode variants of the previously described alternative large T antigen open reading frame (ALTO) protein. Circular ALTO RNAs (circALTOs) can be detected in virus positive Merkel cell carcinoma (VP-MCC) cell lines and tumor samples. CircALTOs are stable, predominantly located in the cytoplasm, and N6-methyladenosine (m6A) modified. The translation of MCPyV circALTOs into ALTO protein is negatively regulated by MCPyV-generated miRNAs in cultured cells. MCPyV ALTO expression increases transcription from some recombinant promoters in vitro and upregulates the expression of multiple genes previously implicated in MCPyV pathogenesis. MCPyV circALTOs are enriched in exosomes derived from VP-MCC lines and circALTO-transfected 293T cells, and purified exosomes can mediate ALTO expression and transcriptional activation in MCPyV-negative cells. The related trichodysplasia spinulosa polyomavirus (TSPyV) also expresses a circALTO that can be detected in infected tissues and produces ALTO protein in cultured cells. Thus, human polyomavirus circRNAs are expressed in human tumors and infected tissues and express proteins that have the potential to modulate the infectious and tumorigenic properties of these viruses.

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