Resolution and recovery
Host transcriptional and chromatin states return to baseline as the epithelium regenerates.
Research
How respiratory viruses reprogram the host cell, and what persists after recovery
Influenza A virus and SARS-CoV-2 alter how the infected cell processes RNA and organises chromatin. Using human airway models, mouse models and long-read multi-omics, we define these changes, the mechanisms that generate them and their consequences after viral clearance.
01
Molecular mechanisms
Infection alters host gene regulation at two levels: RNA processing and translation, and chromatin organisation. We examine how these changes arise, their function during infection, and whether they persist after viral clearance.
01.1
RNA processing
Viral infection generates a diverse repertoire of alternatively processed and translated RNAs and proteins, much of which is missed when analyses are restricted to annotated genes and transcripts. Using long-read sequencing and multi-omics, we identify these infection-specific molecules, define the mechanisms that generate them and determine how they shape host-virus interactions.
Approaches
- Long-read RNA sequencing
- Isoform and reading frame discovery
- RNA modifications such as m6A
- Ribosome profiling
01.2
The epigenome
Infection can profoundly alter the host chromatin landscape, with consequences for gene regulation that may extend beyond the acute phase. We investigate the viral and host factors that drive this epigenetic reprogramming, and map changes in chromatin accessibility and DNA methylation at regulatory regions over the course of infection and recovery.
Approaches
- Chromatin accessibility (ATAC-seq)
- Histone modifications (CUT and RUN)
- DNA methylation
- Recovery time courses
01.3
Recovery or persistence
Following viral clearance, does the epithelium return to its pre-infection state, or does it retain a molecular memory of infection? This question links our work on RNA processing and chromatin to tissue repair and long-term respiratory health.
Persistent dysregulation
Infection-induced changes persist beyond viral clearance, impairing repair and sustaining inflammation.
Determining which outcome prevails, and the mechanisms that govern it, is a central aim of the lab.
02
From discovery to therapy
Mechanistic insight provides the basis for intervention. In the longer term, we aim to translate our findings into strategies that target both the virus and its lasting effects on the host.
- 01
Discovery
Long-read and multi-omic profiling of infected cells to identify infection-specific RNAs, proteins and chromatin states.
- 02
Mechanism
Biochemical and molecular dissection of how these molecules and states arise.
- 03
Function
Perturbation in airway and mouse models to test their effect on infection and recovery.
- 04
Targets
Prioritisation of host and viral factors that drive disease or impair repair.
- Long-term aim
Therapeutic strategies
Translating mechanism into intervention against the virus and its lasting effects on the host, for example with antisense oligonucleotides (ASOs).
- ASOs
Join the lab
We are always looking for curious and motivated individuals who share our passion for RNA and molecular biology, and who bring a sense of fun, curiosity, and adventure to scientific discovery!