Leader

Research Summary

Nature has learnt to wrangle nucleic acids in many ways: from the metres of DNA that are packed into each of our human cells by millions of histone proteins, to the tiny stretches of RNA tucked away within the confines of a virus particle. The physical constraints of nucleic acid structure and packaging must be carefully circumnavigated to allow adaptation and evolution of their owners (from human, to virus). In my lab, we study the molecular processes that drive and constrain viral evolution, with a particular focus on how RNA structure guides RNA recombination and encapsidation. We have a strong interest in studying the role of RNA recombination in virus adaption, particularly in the formation of 'defective viral RNAs'. These genetic species arise spontaneously during virus replication due to non-homologous RNA recombination and can be packaged and transmitted to new cells. They may play important roles in subduing virus replication by interfering with host and viral co-factors required in the virus life-cycle and may also play a role in the stimulation of the host innate immune system. The presence of defective viral RNAs during a viral infection has been demonstrated to influence the severity and outcome of disease and as such may be important biomarkers for prognosis as well as for exploitation in the design of vaccines and anti-viral therapeutics. 

We combine molecular and cellular virology, next-generation sequencing and computational biology to study well-controlled and highly characterized model systems such as Flock House virus, as well as human pathogens including chikungunya virus, zika virus, coronaviruses and HIV. We study systems ranging from controlled cell culture, through animal models, into clinical specimens. This multi-strata approach is aimed at gaining a molecule’s-eye view of the mechanisms of RNA replication and recombination in order to understand virus evolution on a population scale

Routh Lab News

Recent Publications

Mapping RNA-capsid interactions and RNA secondary structure within authentic virus particles using next-generation sequencing

Zhou Y., Routh A.*Nucleic Acids Research, 2020, Jan 24;48(2):e12
gkz1124fig1

Development of Poly(A)-ClickSeq as a Tool Enabling Simultaneous Genome-wide Poly(A)-site identification and Differential Expression Analysis

Elrod N.D., Jaworski E., Ji P., Wagner E.J.*, and Routh A.*,  Methods , 2019, Feb 15, 155:20-29

PACseq-vs-RNAseq_DE
Parallel ClickSeq and Nanopore Sequencing elucidates the rapid evolution of Defective-Interfering RNAs in Flock House virus

Jaworski E. and Routh A., PLoS Pathogens, 2017, May 5, 13(5):e1006365

PLoSPathFig7

Poly(A)-ClickSeq: click-chemistry for next-generation 3´-end sequencing without RNA enrichment or fragmentation. 

Routh A.*, Ji P., Jaworski E., Xia Z., Li W. and Wagner E.J.*  Nucleic Acids Research, 2017, Apr 26, 45(12):e112 

RPL12_PACseq-vs-RNAseq

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