Postdoctoral Training Fellow - Bauer Laboratory
Closing date and time:
14 May 2021 at 23:59
David LV Bauer, Group Leader
This is a full-time, fixed term (4 years, extendable for up to 6 years subject to funding) position on Crick terms and conditions of employment.
The research group: RNA Virus Replication Laboratory
Viruses are infectious parasites that can cause disease. Viruses cannot grow on their own — they must infect a 'host' cell in order to reproduce, and often cause disease in the process. All forms of life, from bacteria and fungi to plants and animals, are infected by at least one type of virus. The RNA Virus Replication Laboratory, led by David LV Bauer, studies the large group of viruses that store their genome as RNA, instead of DNA. They cause a wide range of diseases in humans, from the common cold to more severe illnesses such as gastroenteritis, influenza, Ebola virus disease, measles and COVID-19.
The use of RNA (instead of DNA) by these viruses gives them unique properties since RNA – unlike DNA – can adopt specific shapes that allow the genome itself to carry out structural and enzymatic functions directly, even though it is not a protein or an enzyme in a conventional sense. All RNA viruses exploit this unique property of RNA in one way or another, and hosts have similarly evolved to detect unique features of viral RNA to respond to viral infection.
Our research falls broadly in three areas (1) how RNA viruses replicate and cause disease; (2) how they interact with their hosts and the role of RNA in this process; and (3) how we can apply this information to predict, prevent and treat RNA virus infection and resulting disease.
To work within these areas, our laboratory borrows tools from biochemistry, molecular biology, virology, genomics, and bioinformatics. We use a wide range of model systems (from animals and clinical samples, through to cultured cells and purified in vitro proteins) and take advantage of the Crick’s considerable BSL-3 and ABSL-3 facilities, in vivo imaging, and their integration with our on-site Science and Technology Platforms (Advanced Sequencing, Bioinformatics & Biostatistics, Proteomics, High Throughput Screening, etc.).
Within the Crick, we collaborate with RNA biochemists, cell biologists, immunologists, and virologists – including those at the WIC, one of six WHO Collaborating Centres for Influenza. We have a similar range of collaborators outside of the Crick, as well as two active industrial collaborations, ably supported by the Crick’s Translation Team. Our interests focus on diverse viruses: active projects include double strand, negative strand, and positive strand RNA viruses, with an emphasis on those such as influenza A viruses and coronaviruses that are responsible for human disease. Our lab is also part of the national Genotype-to-Phenotype (G2P-UK) consortium that assesses emerging SARS-CoV-2 variants
We are a diverse group of scientists, from a wide range of backgrounds – scientific and otherwise – and we all strongly believe that our best work comes from working together in a fun, positive, motivating, and exciting atmosphere.
RNA structure plays key roles in virus replication across diverse RNA viruses. Coronaviruses, for example, use RNA structures to regulate their own genome replication, as well as to interact with host ribosomes. Coronaviruses also use RNA structures to guide RNA recombination, which is required for subgenomic mRNA synthesis to express accessory and structural (i.e. Spike, Envelope, Membrane, Nucleocapsid) genes — and underlies the process of coronavirus horizontal gene transfer and evolution. Despite their differences, influenza viruses use RNA structures to carry out similar processes, including the control splicing of viral genes, and the driving of reassortment of their eight genomic segments (Dadonaite, Gilbertson et al., Nat Microbiol, 2019) — the process that gives rise to new pandemic strains.
RNA structure also plays a key role from the perspective of the host response to diverse RNA viruses. Viral RNA contains a number of unique features that act as PAMPs, including CpG content, 5’ triphosphates, and extensive structured (i.e. double-stranded) elements that may trigger an innate immune response. In this context, PAMP generation (and detection) is intrinsically tied to viral replication (te Velthuis, Long, Bauer et al., Nat Microbiol, 2018) — and the persistence of PAMPs may drive prolonged immune signalling.
This research project aims to understand how RNA structure affects virus replication, evolution, and its relationship to the immune response and the host overall. The successful applicant will be given considerable latitude to develop their research direction as part of the Crick’s Postdoc Programme, and to make full use of the unique resources available at the Crick (https://www.crick.ac.uk/careers-and-study/postdocs/postdoc-programme).
Some of the specific aims could include (but are not limited to):
- Exploring how RNA:RNA interactions form during influenza virus infection as it progresses, and how it affects segment bunding and packaging
- Delineating interactions with host RNAs that facilitate this process
- Exploring how RNA structures drive recombination, gene transfer and evolution in coronaviruses
- Comparative analysis of virus/host factors driving recombination and reassortment across RNA viruses
- Determination of immunogenicity of RNA structures in highly-pathogenic RNA virus infections
- Comparison of PAMPs, innate immune activation, clearance, and role in pathogenesis and driving sustained immune activation in respiratory virus infections.
- Collaboration with microscopists (EM, fluorescence), mathematicians, and structural biologists to generate an integrated, multi-scale view of RNA structure and function.
Postdoctoral Training Fellows are expected to lead their own projects, contribute to other projects on a collaborative basis (both in the lab and with external collaborators) and guide PhD students in their research. The ability to work in a team is essential, as is the promotion of an exciting and supportive atmosphere in the lab for all members of the group.
Key experience and competencies
The post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:
- Higher education degree in virology, RNA biology, immunology, or related fields
- Experience with conventional molecular biology techniques (cloning, gel electrophoresis, western blotting, etc.)
- Motivation to perform cutting-edge science using various tools to understand different aspects of RNA virus function
- Strong multitasking ability, capability to handle highly dynamic projects, and openness to learning new techniques
- Strong skills in organising and thorough record-keeping
- Strong collaborative ability and teamwork experience
- Track record of writing papers as evidenced by publications or submitted manuscripts in refereed journals
- Evidence of data presentation at scientific meetings
- Experience of experimental design
- Ability to work independently and also capable of interacting within a group
- Encouragement of a positive, motivating, and supportive lab atmosphere
- Experience in research with RNA viruses
- Experience in research on RNA structure and function
- Experience with high-throughput sequencing and associated bioinformatic analysis
- Prior experience with animal models of viral infection or innate immunity
- Experience of working in a containment laboratory setting carrying out virus culture and characterisation
- Experience in virus reverse genetics / rescue