Research Themes

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Resolving the genomic and ecologial drivers of pathogens.

Infectious diseases have historically represented the most common cause of death in humans. Apart from a few pathogens, that may have co-speciated with their human host, most infectious diseases we face have been acquired through host jumps from wild or domesticated animal hosts or sometimes from the wider environment. The timing of these events and the original sources remains unclear in many cases.

Large-scale genomic datasets offer opportunites to resolve the age of emergence of disease causing agents as well as the factors which have been important in their transmission and spread in humans and other hosts. There is however no one-size-fits-all analysis applicable to all pathogen species if we hope to obtain genuinely relevant biologically insights. Whilst this creates challenges, it also opens up room for the development of methodological frameworks flexible enough to be adapted to an array of pathogens and to questions that have direct impact on human health.

Age of emergence of significant infectious diseases impacting on human populations. Adapted from Balloux & van Dorp (2017), BMC Biology. 15,91.

Age of emergence of significant infectious diseases impacting on human populations. Adapted from Balloux & van Dorp (2017), BMC Biology. 15,91.

Relevant publications

van Dorp L, Acman M, Richard D, Shaw LP, Ford CE, Ormond L, Owen CJ, Pang J, Tan CS C, Boshier AT F, Torres Ortiz A, Balloux F. Emergence of genomic diversity and recurrent mutations in SARS-CoV-2. (2020) Infection Genetics & Evolution.

Osnes MN, van Dorp L, Brynildsrud OB, Alfsnes K, TSchneiders T, Templeton KE, Yahara K, Balloux F, Caugant DA, Eldholm V. Antibiotic treatment regimes as a driver of the global population dynamics of a major gonorrhea lineage. (2020) MBE.

Farrer RA, Chang M, Davis M, van Dorp L, Yang DH, Shea T, Sewell T, Meyer W, Balloux F, Edwards H, Chanda D, Kwenda G, Vanhove M, Chang YC, Cuomo CA, Fisher MC, Kwon-Chung KJ. A new lineage of Cryptococcus gattii (VGV) discovered in the Central Zambezi miombo woodlands. (2019) MBio.

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Genomic characterisation of the acquisition and transmission of AMR.

The rapid, global increase in the burden of antimicrobial resistance (AMR) elements/mutations and virulence factors in microbial pathogens constitutes a major challenge in healthcare and veterinary medicine worldwide. Most bacterial pathogens considered as AMR threats readily exchange genetic material through horizontal gene transfer (HGT) predominately mediated by plasmids and plasmid-borne transposable elements - 'jumping genes'. A notable exception is Mycobacterium tuberculosis, which evolves clonally with resistance mediated by point mutations.

Phylogenetic models coupled with statistical genetics offer opportunities to identify AMR gene candidates as well as the underlying processes giving rise to their global prevalence. For example, our work on the plasmid-borne colistin resistance element mcr-1 highlights just how quickly resistance can spread; in this case from a likely livestock origin in Asia to a global distribution in the space of only a decade (see here for details).

Alignment over the mcr-1 composite transposon across a global dataset of bacteria carrying mcr-1. Adapted from Wang, van Dorp & Shaw et al. (2018)., Nature Communications. 9,1179.

Alignment over the mcr-1 composite transposon across a global dataset of bacteria carrying mcr-1. Adapted from Wang, van Dorp & Shaw et al. (2018)., Nature Communications. 9,1179.

Relevant publications

Acman M, Wang R, van Dorp L, Shaw L, Wang Q, Luhmann N, Yin Y, Sun S, Chen H, Wang H, Balloux F. Role of the mobilome in the global dissemination of the carbapenem resistance gene blaNDM. (2022) Nature Communications. 13, 1131.

van Dorp L, Wang Q, Shaw L, Ding C, Wang R, Gao H, Yin Y, Farrer R, Didelot X, Balloux F, Wang H. Rapid phenotypic evolution in multidrug-resistant Klebsiella pneumoniae hospital outbreak strains. (2019) Microbial Genomics. 5, 000263.

Balloux F, Brynildsrud O, van Dorp L, Shaw LP, Chen H, Harris KA, Wang H, Eldholm V. From Theory to Practice: Translating Whole-Genome Sequencing (WGS) into the Clinic. (2018) Trends in Microbiology. 26, 1035-1048.

Wang R, van Dorp L, Shaw L, Bradley P, Wang A, Wang X, Jin L, Zhang Q, Liu Y, Rieux A, Dorai-Schneiders T, Weinert L A, Iqbal Z, Didelot X, Wang H+, Balloux F. The global distribution and spread of the mobilized colistin resistance gene mcr-1. (2018) Nature Communications. 9, 1179.

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SARS-CoV-2 and the coronaviridae.

The ongoing COVID-19 pandemic has put coronaviruses in the spotlight as major multihost zoonotic viral pathogens. There are seven coronaviruses known to widely infect humans (HCoVs). Each of SARS-CoV-2, SARS-CoV-1 and SARS-MERS have jumped into the human population over the course of the last twenty years, leading to epidemic and pandemic scale diseases, while four HCoVs circulate endemically in human populations and frequently cause common colds. To date, at least 155 species of coronavirus are known to circulate in a diverse array of vertebrate populations and the host-range and zoonotic potential of many of these species remains largely unknown.

Core genome phylogeny and associated hosts for members of the Coronaviridae. The seven coronaviruses known to have infected humans are highlighted on the inner ring.

Core genome phylogeny and associated hosts for members of the Coronaviridae. The seven coronaviruses known to have infected humans are highlighted on the inner ring.

The first genome sequence of SARS-CoV-2, the agent of COVID-19, was made available in early January 2020. Since then many thousands of SARS-CoV-2 genome assemblies have been shared by the research community providing unprecedented opportunities to track the emergence of genomic diversity in SARS-CoV-2 in close to real time. This has allowed insights to be gleaned on the nature of transmission in different countries around the world as well as facilitating careful characterisation of the distribution of mutations in SARS-CoV-2, including those putatively under selection.

Our work has focused on characterising the age and origins of SARS-CoV-2 as well as formerly testing for sites under selection in this new human pandemic virus.

Relevant publications

Escalera-Zamudio M, Kosakovzky Pond S, (…), van Dorp L, (…), Pybus O, Hulswit R (11 auth). Identification of site-specific evolutionary trajectories shared across human betacoronaviruses. (2023) GBE. 15, 6, evad076.

Tan CCS, Trew J, Peacock T, (…), van Dorp L, Balloux, Savolainen (24 auth). Surveillance of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential. (2023) Nature Communications. 14, 3322.

Balloux F, Tan CCS, Swadling L, Richard D, Jenner C, Maini M, van Dorp L. The past, current and future immunogenetic dynamic of SARS-CoV-2. (2022) Oxford Open Immunology. 3, 1, iqac003.

Tan CCS, Lam C, Richard D, Owen C, Berchtold T, Orengo C, Nair MS, Kuchipudi SV, Kapur V, van Dorp L, Balloux F. Transmission of SARS-CoV-2 from humans to animals and potential host adaptation. (2022) Nat Comms. 13, 2988.

Tan CCS, Owen C, Tham C, Bertoletti A, van Dorp L, Balloux F. Pre-existing T cell-mediated cross-reactivity to SARS-CoV-2 cannot solely be explained by prior exposure to endemic human coronaviruses. (2020) Infect. Genet. Evol. 95, 105075.

van Dorp L, Houldcroft C, Richard D, Balloux F. COVID-19, the first pandemic in the post-genomic era. (2021) Current Opinions in Virology. 50, 40-48.

Qutob N, Salah Z, Richard D, Darwish H, Sallam H, Shtayeh I, Najjar O, Ruzayqat M, Najjar D, Balloux F, van Dorp L. The genomic epidemiology of SARS-CoV-2 in Palestine. (2021) Microbial Genomics. 7,000584.

Lam SD, Bordin N, Waman VP, Scholes HM, Ashford P, Sen N, van Dorp L, Rauer C, Dawson NL, Pang CSM, Abbasian M, Sillitoe I, Edwards SJL, Fraternali F, Lees JG, Santini JM, Orengo CA. SARS-CoV-2 spike protein predicted to bind strongly to host receptor protein orthologues from mammals, but not fish, birds or reptiles. (2020) Scientific Reports.

van Dorp L, Richard D, Tan CS., Shaw LP, Acman M, Balloux F. No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2. (2020) Nature Communications. 11,5986.

van Dorp L, Acman M, Richard D, Shaw LP, Ford CE, Ormond L, Owen CJ, Pang J, Tan CS C, Boshier AT F, Torres Ortiz A, Balloux F. Emergence of genomic diversity and recurrent mutations in SARS-CoV-2. (2020) Infection Genetics & Evolution.

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Using the resource of ancient and historic genomes to inform studies of infectious disease evolution.

Genomic data from current pathogens can be used to reconstruct disease outbreaks and pandemics in space and time, providing direct evidence for the source of an infection and its spread. However, genomic data can also increasingly be obtained for historical and ancient pathogens from materials such as archaeological remains, medical collections or even old papers.

Genomes of ancient pathogens can be combined with modern ones into a single analytical framework that sheds new light on the interactions between pathogens and us, their human hosts. Such analyses commonly reveal the presence of extinct lineages, which cannot be recovered from modern data alone, the inclusion of which have allowed more accurate phylogenetic estimates of pathogen evolutionary rates.

Shot-gun sequencing of ancient DNA provides a plethora of information on the ancient host and associated microbial (pathogen) content.

Shot-gun sequencing of ancient DNA provides a plethora of information on the ancient host and associated microbial (pathogen) content.

As an example, our recent work was the first to analyse the genomes of eradicated European P. vivax and P. falciparum, sequenced from antique slides prepared in 1944 from malaria-affected patients in the Ebro Delta of Spain. Using a mixture of phylogenetic and population genetics analyses, we inferred the contribution of eradicated strains to global dispersals. European P. falciparum showed a close affinity to Central-South-Asian rather than African strains. Conversely, European P. vivax had a close genetic relationship to strains currently in the Americas. Phylogenetic dating methods estimated the introduction of the parasite to the Americas to the 15th century, consistent with an introduction associated with European colonialism. Both eradicated European strains were in circulation prior to the use of modern antimalarials highlighting how historic genomes can be used to inform on not only past events but also phenotypic traits of clinical relevance today.

Eradicated European P. vivax sequenced from medical microscopy slides demonatrates a close affinity to the Americas.

Eradicated European P. vivax sequenced from medical microscopy slides demonatrates a close affinity to the Americas.

Relevant publications

Guellil M, van Dorp L, Inskip SA, Dittmar JM, Saag L, Tambets K, Hui R, Rose A, D’Atanasio E, Kriiska A, Varul L, Koekkelkoren A, Goldina RD, Cessford C, Solnik A, Metspalu M, Krause J, Herbig A, Robb JE, Houldcroft C, Scheib C. Ancient herpes simplex 1 genomes reveal recent viral structure in Eurasia. (2022) Science Advances. 8, 30, eabo4435.

White, de-Dios, Carrión, Bonora, Llovera, Cilli, Lizano, Khabdulina, Tleugabulov, Olalde, Marquès-Bonet, Balloux, Pettener, van Dorp, Luiselli, Lalueza-Fox. Genomic analysis of 18th-century Kazakh individuals and their oral microbiome. (2021) Biology. 10 (12), 1324.

de Dios T, Carrion, Olalde, Nadal (…) van Dorp L, Lalueza-Fox. Ancient Salmonella enterica from a soldier of the 1652-siege of Barcelona (Spain) supports historical epidemic contacts across the Atlantic. (2021) iScience. 9, 24.

van Dorp L, Gelabert P*, Rieux A, de Manuel M, de-Dios A, Gopalakrishnan S, Carøe C, Sandoval-Velasco M, Fregel R, Olalde I, Escosa R, Aranda C, Huijben H, Mueller I, Marquès-Bonet T, Balloux F, Gilbert MTP, Lalueza-Fox C. Plasmodium vivax Malaria viewed through the lens of an eradicated European strain. (2019) Molecular Biology and Evolution, msz264.

de-Dios T, van Dorp L, Gelabert P, Carøe C, Sandoval-Velasco M, Fregel R, Escosa R, Aranda C, Huijben S, Balloux F, Gilbert T, Lalueza-Fox C. Genetic affinities of an eradicated Plasmodium falciparum European strain. (2019) Microbial Genomics. 000289.

de-Dios T, van Dorp L, Charlier P, Morfopoulou S, Lizano E, Bon C, Le Bitouzé C, Álvarez-Estapé M, Marquès-Bonet T, Balloux F+, Lalueza-Fox C. Metagenomic analysis of a blood stain from the French revolutionary Jean-Paul Marat (1743-1793). (2020) Infection Genetics & Evolution. 80, 104209.

Brace S, Diekmann Y, Booth TJ, van Dorp L, Faltyskova Z, Rohland N, Mallick S, Olalde I, Ferry M, Michel M, Oppenheimer J, Broomandkhoshbacht N, Stewardson K, Martiniano R, Walsh S, Kayser M, Charlton S, Hellenthal G, Armit I, Schulting R, Craig O E, Sheridan A, Pearson M P, Stringer C, Reich D, Thomas M G, Barnes I. Ancient genomes indicate population replacement in Early Neolithic Britain. (2019) Nature Ecology & Evolution. 3, 765–771.