Dr Adrian Smith
My research is focussed on understanding the basis of immunity to infectious challenge and includes studies of immune mechanisms that operate in different vertebrate species (particularly birds and mammals). I have a special interest in the mechanisms of immunity in the gut and how different subsets of T lymphocytes contribute to protective immunity. Many responses are stimulated during infection but it is clear that only a subset of the response is involved in protective immunity. A central theme of the work of my group is directed towards defining which of the induced responses and cellular interactions are effective in pathogen control.
Current projects include the comparative biology of pattern recognition receptors, TCRαβ and TCRγδ T cell biology, parasite genetics as a tool to define protective antigen-encoding loci and the mechanisms of immunity against infection. Currently our focus is on immunity to parasitic protozoa (e.g. Eimeria spp) and bacterial (e.g. Salmonella enterica) pathogens. The knowledge gained in these studies contributes to our understanding of the basic biology of immune systems, provides an integrated view of host-pathogen interactions and contributes towards development of effective immune interventions (e.g. vaccines).
Additional Information
In 2007 my colleagues and I received the Daiwa Foundation Lord Adrian Prize for our studies on enteric T cell function (with Dr Kyoko Inagaki-Ohara and Prof Goro Matsuzaki). I also hold Jenner Investigator status in recognition of contributions to vaccine development.
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Intestinal helminths as a biomolecular complex in archaeological research
November 2020|Journal article|Philosophical Transactions of the Royal Society B: Biological Sciences -
A review of a decade of lessons from one of the world’s largest MPAs: conservation gains and key challenges
November 2020|Journal article|Marine Biology© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Given the recent trend towards establishing very large marine protected areas (MPAs) and the high potential of these to contribute to global conservation targets, we review outcomes of the last decade of marine conservation research in the British Indian Ocean Territory (BIOT), one of the largest MPAs in the world. The BIOT MPA consists of the atolls of the Chagos Archipelago, interspersed with and surrounded by deep oceanic waters. Islands around the atoll rims serve as nesting grounds for sea birds. Extensive and diverse shallow and mesophotic reef habitats provide essential habitat and feeding grounds for all marine life, and the absence of local human impacts may improve recovery after coral bleaching events. Census data have shown recent increases in the abundance of sea turtles, high numbers of nesting seabirds and high fish abundance, at least some of which is linked to the lack of recent harvesting. For example, across the archipelago the annual number of green turtle clutches (Chelonia mydas) is ~ 20,500 and increasing and the number of seabirds is ~ 1 million. Animal tracking studies have shown that some taxa breed and/or forage consistently within the MPA (e.g. some reef fishes, elasmobranchs and seabirds), suggesting the MPA has the potential to provide long-term protection. In contrast, post-nesting green turtles travel up to 4000 km to distant foraging sites, so the protected beaches in the Chagos Archipelago provide a nesting sanctuary for individuals that forage across an ocean basin and several geopolitical borders. Surveys using divers and underwater video systems show high habitat diversity and abundant marine life on all trophic levels. For example, coral cover can be as high as 40–50%. Ecological studies are shedding light on how remote ecosystems function, connect to each other and respond to climate-driven stressors compared to other locations that are more locally impacted. However, important threats to this MPA have been identified, particularly global heating events, and Illegal, Unreported and Unregulated (IUU) fishing activity, which considerably impact both reef and pelagic fishes. -
Identification and Distribution of Novel Cressdnaviruses and Circular molecules in Four Penguin Species in South Georgia and the Antarctic Peninsula.
September 2020|Journal article|VirusesThere is growing interest in uncovering the viral diversity present in wild animal species. The remote Antarctic region is home to a wealth of uncovered microbial diversity, some of which is associated with its megafauna, including penguin species, the dominant avian biota. Penguins interface with a number of other biota in their roles as marine mesopredators and several species overlap in their ranges and habitats. To characterize the circular single-stranded viruses related to those in the phylum <i>Cressdnaviricota</i> from these environmental sentinel species, cloacal swabs (<i>n</i> = 95) were obtained from King Penguins in South Georgia, and congeneric Adélie Penguins, Chinstrap Penguins, and Gentoo Penguins across the South Shetland Islands and Antarctic Peninsula. Using a combination of high-throughput sequencing, abutting primers-based PCR recovery of circular genomic elements, cloning, and Sanger sequencing, we detected 97 novel sequences comprising 40 ssDNA viral genomes and 57 viral-like circular molecules from 45 individual penguins. We present their detection patterns, with Chinstrap Penguins harboring the highest number of new sequences. The novel Antarctic viruses identified appear to be host-specific, while one circular molecule was shared between sympatric Chinstrap and Gentoo Penguins. We also report viral genotype sharing between three adult-chick pairs, one in each Pygoscelid species. Sequence similarity network approaches coupled with Maximum likelihood phylogenies of the clusters indicate the 40 novel viral genomes do not fall within any known viral families and likely fall within the recently established phylum <i>Cressdnaviricota</i> based on their replication-associated protein sequences. Similarly, 83 capsid protein sequences encoded by the viruses or viral-like circular molecules identified in this study do not cluster with any of those encoded by classified viral groups. Further research is warranted to expand knowledge of the Antarctic virome and would help elucidate the importance of viral-like molecules in vertebrate host evolution. -
The Potential Role of Endogenous Viral Elements in the Evolution of Bats as Reservoirs for Zoonotic Viruses.
September 2020|Journal article|Annual review of virologyDespite a small genome size, bats have comparable diversity of retroviral and non-retroviral endogenous sequences to other mammals. These include Class I and Class II retroviral sequences, foamy viruses, and deltaretroviruses, as well as filovirus, bornavirus, and parvovirus endogenous viral elements. Some of these endogenous viruses are sufficiently preserved in bat genomes to be expressed, with potential effects for host biology. It is clear that the bat immune system differs when compared with other mammals, yet the role that virus-derived endogenous elements may have played in the evolution of bat immunity is poorly understood. In this review, we discuss some of the bat-specific immune mechanisms that may have resulted in a virus-tolerant phenotype and link these to the long-standing virus-host coevolution that may have allowed a large diversity of endogenous retroviruses and other endogenous viral elements to colonize bat genomes. We also consider the possible effects of endogenization in the evolution of the bat immune system. -
Epidemiological insights from a large-scale investigation of intestinal helminths in Medieval Europe.
August 2020|Journal article|PLoS Neglected Tropical Diseases -
Evidence of Pathogen-Induced Immunogenetic Selection across the Large Geographic Range of a Wild Seabird.
June 2020|Journal article|Molecular biology and evolutionOver evolutionary time, pathogen challenge shapes the immune phenotype of the host to better respond to an incipient threat. The extent and direction of this selection pressure depend on the local pathogen composition, which is in turn determined by biotic and abiotic features of the environment. However, little is known about adaptation to local pathogen threats in wild animals. The Gentoo penguin (Pygoscelis papua) is a species complex that lends itself to the study of immune adaptation because of its circumpolar distribution over a large latitudinal range, with little or no admixture between different clades. In this study, we examine the diversity in a key family of innate immune genes-the Toll-like receptors (TLRs)-across the range of the Gentoo penguin. The three TLRs that we investigated present varying levels of diversity, with TLR4 and TLR5 greatly exceeding the diversity of TLR7. We present evidence of positive selection in TLR4 and TLR5, which points to pathogen-driven adaptation to the local pathogen milieu. Finally, we demonstrate that two positively selected cosegregating sites in TLR5 are sufficient to alter the responsiveness of the receptor to its bacterial ligand, flagellin. Taken together, these results suggest that Gentoo penguins have experienced distinct pathogen-driven selection pressures in different environments, which may be important given the role of the Gentoo penguin as a sentinel species in some of the world's most rapidly changing environments. -
Receding ice drove parallel expansions in Southern Ocean penguins.
December 2019|Journal article|Proceedings of the National Academy of Sciences of the United States of AmericaClimate shifts are key drivers of ecosystem change. Despite the critical importance of Antarctica and the Southern Ocean for global climate, the extent of climate-driven ecological change in this region remains controversial. In particular, the biological effects of changing sea ice conditions are poorly understood. We hypothesize that rapid postglacial reductions in sea ice drove biological shifts across multiple widespread Southern Ocean species. We test for demographic shifts driven by climate events over recent millennia by analyzing population genomic datasets spanning 3 penguin genera (<i>Eudyptes</i>, <i>Pygoscelis</i>, and <i>Aptenodytes</i>). Demographic analyses for multiple species (macaroni/royal, eastern rockhopper, Adélie, gentoo, king, and emperor) currently inhabiting southern coastlines affected by heavy sea ice conditions during the Last Glacial Maximum (LGM) yielded genetic signatures of near-simultaneous population expansions associated with postglacial warming. Populations of the ice-adapted emperor penguin are inferred to have expanded slightly earlier than those of species requiring ice-free terrain. These concerted high-latitude expansion events contrast with relatively stable or declining demographic histories inferred for 4 penguin species (northern rockhopper, western rockhopper, Fiordland crested, and Snares crested) that apparently persisted throughout the LGM in ice-free habitats. Limited genetic structure detected in all ice-affected species across the vast Southern Ocean may reflect both rapid postglacial colonization of subantarctic and Antarctic shores, in addition to recent genetic exchange among populations. Together, these analyses highlight dramatic, ecosystem-wide responses to past Southern Ocean climate change and suggest potential for further shifts as warming continues. -
Comparative micro-epidemiology of pathogenic avian influenza virus outbreaks in a wild bird population.
June 2019|Journal article|Philosophical transactions of the Royal Society of London. Series B, Biological sciencesUnderstanding the epidemiological dynamics of highly pathogenic avian influenza virus (HPAIV) in wild birds is crucial for guiding effective surveillance and control measures. The spread of H5 HPAIV has been well characterized over large geographical and temporal scales. However, information about the detailed dynamics and demographics of individual outbreaks in wild birds is rare and important epidemiological parameters remain unknown. We present data from a wild population of long-lived birds (mute swans; Cygnus olor) that has experienced three outbreaks of related H5 HPAIVs in the past decade, specifically, H5N1 (2007), H5N8 (2016) and H5N6 (2017). Detailed demographic data were available and intense sampling was conducted before and after the outbreaks; hence the population is unusually suitable for exploring the natural epidemiology, evolution and ecology of HPAIV in wild birds. We show that key epidemiological features remain remarkably consistent across multiple outbreaks, including the timing of virus incursion and outbreak duration, and the presence of a strong age-structure in morbidity that likely arises from an equivalent age-structure in immunological responses. The predictability of these features across a series of outbreaks in a complex natural population is striking and contributes to our understanding of HPAIV in wild birds. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. This issue is linked with the subsequent theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'.Animals, Animals, Wild, Anseriformes, Influenza A virus, Disease Outbreaks, Phylogeny, Influenza A Virus, H5N1 Subtype, Influenza in Birds, United Kingdom
E: | adrian.smith@zoo.ox.ac.uk |
T: | 01865 (2) 71195 |