RNA transmission and function in host-pathogen interactions. Amy Buck is a Professor of RNA and Infection Biology in the Institute of Immunology & Infection Research. Her research focuses on understanding the molecular mechanisms by which non-coding RNAs and RNA-binding proteins alter immune signalling during infections. Her lab studies both intracellular RNA biology (how viruses manipulate RNA interference pathways) and extracellular RNA biology (how parasites transmit their RNAs into host cells and how this RNA signals information). Her work uses molecular and biochemical techniques combined with proteomic, sequencing and imaging methodologies to probe non-coding RNA mechanisms and functions at subcellular, cellular, tissue and organismal scales. Amy Buck Amy earned her PhD in Biochemistry at the University of Colorado, Boulder, in 2005 where she studied RNA-protein dynamics in the RNase P ribozyme in the lab of Prof. Norman Pace. She then joined the Division of Pathway Medicine at the University of Edinburgh and secured an Incoming Marie Curie Fellowship to focus on the biology and functions of microRNAs in viral infection. In 2009, she started her own lab within the Institute of Immunology & Infection Research as part of the Wellcome Trust funded Centre for Immunity, Infection & Evolution, focusing on RNA functions in viral-host interactions and initiating a new line of research on RNA secretion in parasite infections. Amy was awarded a Wellcome Trust Research Career Development Fellowship in 2012 and an ERC Consolidator Award in 2020 and led the COST Action exRNA-PATH from 2021-2025. Buck Lab Website Lab members Kyriaki Neophytou, Elaine Robertson, and David Wright Research How does RNA communicate information between cells and species in the gut?The mammalian gut is a complex ecosystem of different organisms that communicate to share resources, coordinate digestion and maintain homeostasis. In many animals, parasitic nematodes are part of this ecosystem (Fig. 1), where they promote tolerance and modulate the gut environment to favour their survival. Our lab discovered that gastrointestinal nematodes release RNAs and an Argonaute protein both inside and outside of extracellular vesicles and these are internalized by host cells [1]. The transmission of these complexes appears important for parasite survival and the nematode Argonaute protein is a novel antigen that we are now testing as a vaccine against nematode parasites [2].Our over-arching goal is to build a quantitative and molecular model for how parasite RNAs are functionally transmitted to the host and this involves questions across several scales: How are RNAs selected for export from the parasite, and what regions in the genome do these come from? Which RNA-protein complexes enter cells and how do these RNAs then signal information? What defines the specificity of transmission to host cells (stem cells) and how does this impact the chronic infection? Can we block RNA transmission to control parasites, and/or can we harness the mechanisms used by parasites to develop better delivery strategies for RNA drugs? Figure 1. Heligmosomoides bakeri is a nematode parasite that establishes chronic infection in the mouse small intestine (left) and releases natural products including extracellular vesicles (right, top) and RNA-protein complexes that directly enter host cells. We study the specific cells that are targeted by the parasites in the epithelium using a variety of approaches including organoids (right, bottom). How do viruses disrupt cellular RNAi pathways and does this signal information beyond the infected cell? As intracellular obligate parasites, viruses provide unique models to understand how foreign RNAs can enter host RNAi pathways, how the RNAi pathways are regulated and how RNAs are transmitted and signal from one cell to another. We have used biochemical methods to identify viral RNAs that bind and sequester or directly target (for degradation) cellular miRNAs, leading to de-regulation of host gene expression [3, 4]. Interestingly, our work suggests that some microRNAs bound to human Argonaute 2 target long non-coding RNAs and pseudogenes in the nucleus, and may thereby regulate transcription of neighbouring genes [4]. We are characterizing these non-canonical RNAi pathways and how they are regulated in herpesvirus and respiratory virus infections, and anticipate that these hidden aspects of Argonaute biology may be relevant to many other diseases. In parallel, we are interested in which viral-derived or host de-regulated RNAs can signal information beyond infected cells. How do specific RNAs and their associated proteins get exported from infected cells and which of these RNAs reach other cells at sufficient concentrations? How does imported RNA signal within receiving cells and does this operate as a guide for RNAi and/or trigger with TLRs [5]? Selected publications 1. Buck AH, Coakley G, Simbari F, McSorley HJ, Quintana JF, Le Bihan T, Kumar S, Abreu-Goodger C, Lear M, Harcus Y et al: Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nat Commun 2014, 5:5488.2. Neophytou K, Martinez-Ugalde I, Fenton T, Robertson E, Strachan LJ, Harcus Y, Naar CM, Wright D, Price DRG, White R et al: A non-vesicular Argonaute protein is transmitted from nematode to mouse and is important for parasite survival. EMBO Reports 2025 In press & bioRxiv https://doi.org/10.1101/2025.04.01.6465443. Libri V, Helwak A, Miesen P, Santhakumar D, Borger JG, Kudla G, Grey F, Tollervey D, Buck AH: Murine cytomegalovirus encodes a miR-27 inhibitor disguised as a target. PNAS 2012, 109(1):279-284.4. Ressel S, Kumar S, Bermudez-Barrientos JR, Gordon K, Lane J, Wu J, Abreu-Goodger C, Schwarze J, Buck AH: RNA-RNA interactions between respiratory syncytial virus and miR-26 and miR-27 are associated with regulation of cell cycle and antiviral immunity. Nucleic Acids Res 2024, 52(9):4872-4888.5. Tosar JP, Buck AH: mGem: Guides or triggers? Extracellular RNAs beyond vesicular miRNAs. mBio 2025, 16(10):e0312924. This article was published on 2026-04-23
