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Hire Dr. Sara S.
Portugal
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Laboratory Director, expert in host-pathogen interactions

Profile Summary
Subject Matter Expertise
Services
Writing Medical Writing, Newswriting, General Proofreading & Editing
Work Experience

Scientific Consultant

Freelancer

September 2024 - Present

Group Leader and Invited Assistant Professor

Universidade Católica Portuguesa

September 2023 - Present

Post-doctoral Investigator

Universidade de Lisboa Instituto de Medicina Molecular João Lobo Antunes

October 2018 - August 2023

Research Associate

University of Liverpool

September 2017 - September 2018

Research intern

London School of Hygiene & Tropical Medicine

September 2012 - July 2013

Education

PhD Veterinary Parasitology (Infection Biology)

University of Liverpool

August 2014 - June 2018

BSc (Hons) Biomedical Sciences with extramural year

King's College London

September 2010 - June 2014

Certifications
  • Research Integrity

    Epigeum

    August 2024 - Present

  • Laboratory Animal Science EU Functions A, B C, and D (Animal Experimentation, Experimental Design, Project Design)

    Direção Geral de Alimentação e Veterinária

    January 2024 - Present

  • Building and Leading High Performing Teams

    Team Coaching Europe

    October 2023 - Present

  • "la Caixa" Foundation Fellows

    "la Caixa" Foundation

    September 2023 - Present

  • Leadership and Management Skills Course for Postdocs

    HFP CONSULTING

    January 2021 - Present

  • EMBL Project Management for Postdocs

    EMBL

    October 2020 - Present

  • Programming for Life Sciences

    University of Liverpool

    June 2015 - Present

  • Advanced Statistics for the Life Sciences

    University of Liverpool

    June 2015 - Present

Publications
JOURNAL ARTICLE
Investigation of Trypanosoma-induced vascular damage sheds insights into Trypanosoma vivax sequestration @article{ac3050d4a15142a6a198a6aba81f9107, title = "Investigation of Trypanosoma-induced vascular damage sheds insights into Trypanosoma vivax sequestration", abstract = "Multiple blood-borne pathogens infecting mammals establish close interactions with the host vascular endothelium as part of their life cycles. In this work, we investigate differences in the interactions of three Trypanosoma species: T. brucei, T. congolense and T. vivax with the blood vasculature. Infection with these species results in vastly different pathologies, including different effects on vascular homeostasis, such as changes in vascular permeability and microhemorrhages. While all three species are extracellular parasites, T. congolense is strictly intravascular, while T. brucei is capable of surviving both extra- and intravascularly. Our knowledge regarding T. vivax tropism and its capacity of migration across the vascular endothelium is unknown. In this work, we show for the first time that T. vivax parasites sequester to the vascular endothelium of most organs, and that, like T. congolense, T. vivax Y486 is largely incapable of extravasation. Infection with this parasite species results in a unique effect on vascular endothelium receptors including general downregulation of ICAM1 and ESAM, and upregulation of VCAM1, CD36 and E-selectin. Our findings on the differences between the two sequestering species (T. congolense and T. vivax) and the non-sequestering, but extravasating, T. brucei raise important questions on the relevance of sequestration to the parasite's survival in the mammalian host, and the evolutionary relevance of both sequestration and extravasation.", keywords = "Extravasation, Host-pathogen interactions, Intravital microscopy, Parasitology, Sequestration, Trypanosoma", author = "Pereira, {Sara Silva} and Daniela Br{\'a}s and Teresa Porqueddu and Nascimento, {Ana M.} and Niz, {Mariana de}", note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)", year = "2023", month = dec, day = "15", doi = "10.1016/j.tcsw.2023.100113", language = "English", volume = "10", journal = "The Cell Surface", issn = "2468-2330", publisher = "Elsevier BV", } . The Cell Surface.
Transcriptomic profiling of Trypanosoma congolense mouthpart parasites from naturally infected flies @article{f9632c5ef4ee492fae6254a46579c357, title = "Transcriptomic profiling of Trypanosoma congolense mouthpart parasites from naturally infected flies", abstract = "Background: Animal African trypanosomiasis, or nagana, is a veterinary disease caused by African trypanosomes transmitted by tsetse flies. In Africa, Trypanosoma congolense is one of the most pathogenic and prevalent causes of nagana in livestock, resulting in high animal morbidity and mortality and extensive production losses. In the tsetse fly, parasites colonise the midgut and eventually reach the mouthparts, from where they can be transmitted as the fly feeds on vertebrate hosts such as cattle. Despite the extreme importance of mouthpart-form parasites for disease transmission, very few global expression profile studies have been conducted in these parasite forms. Methods: Here, we collected tsetse flies from the Shimba Hills National Reserve, a wildlife area in southeast Kenya, diagnosed T. congolense infections, and sequenced the transcriptomes of the T. congolense parasites colonising the mouthparts of the flies. Results: We found little correlation between mouthpart parasites from natural and experimental fly infections. Furthermore, we performed differential gene expression analysis between mouthpart and bloodstream parasite forms and identified several surface-expressed genes and 152 novel hypothetical proteins differentially expressed in mouthpart parasites. Finally, we profiled variant antigen expression and observed that a variant surface glycoprotein (VSG) transcript belonging to T. congolense phylotype 8 (i.e. TcIL3000.A.H_000381200), previously observed to be enriched in metacyclic transcriptomes, was present in all wild-caught mouthpart samples as well as bloodstream-form parasites, suggestive of constitutive expression. Conclusion: Our study provides transcriptomes of trypanosome parasites from naturally infected tsetse flies and suggests that a phylotype 8 VSG gene is constitutively expressed in metacyclic- and bloodstream-form parasites at the population level. Graphical Abstract: [Figure not available: see fulltext.].", keywords = "Animals, Cattle, Diptera/genetics, Humans, Kenya, Membrane Glycoproteins/genetics, Parasites/genetics, Transcriptome, Trypanosoma congolense/genetics, Trypanosomiasis, African, Tsetse Flies/parasitology", author = "Pereira, {Sara Silva} and Kawira Mathenge and Daniel Masiga and Andrew Jackson", note = "Funding Information: This work was supported by grants from the Biotechnology and Biological Sciences Research Council (BB/M022811/1 and BB/R021139/1) to APJ. SSP is funded by Horizon 2020 through a Marie Sk{\l}odowska-Curie Individual Standard European Fellowship, under Grant Agreement No. 839960. Publisher Copyright: {\textcopyright} 2022, The Author(s).", year = "2022", month = dec, doi = "10.1186/s13071-022-05258-y", language = "English", volume = "15", pages = "1--11", journal = "Parasites and Vectors", issn = "1756-3305", publisher = "BioMed Central Ltd.", number = "1", } . Parasites and Vectors.
Immunopathology and Trypanosoma congolense parasite sequestration cause acute cerebral trypanosomiasis @article{49083f3fda014070ba934a6cfcea8f69, title = "Immunopathology and Trypanosoma congolense parasite sequestration cause acute cerebral trypanosomiasis", abstract = "Trypanosoma congolense causes a syndrome of variable severity in animals in Africa. Cerebral trypanosomiasis is a severe form, but the mechanism underlying this severity remains unknown. We developed a mouse model of acute cerebral trypanosomiasis and characterized the cellular, behavioral and physiological consequences of this infection. We show large parasite sequestration in the brain vasculature for long periods of time (up to 8 hours) and extensive neuropathology that associate with ICAM1-mediated recruitment and accumulation of T cells in the brain parenchyma. Antibody-mediated ICAM1 blocking and lymphocyte absence reduce parasite sequestration in the brain and prevent the onset of cerebral trypanosomiasis. Here, we establish a mouse model of acute cerebral trypanosomiasis and we propose a mechanism whereby parasite sequestration, host ICAM1, and CD4+ T cells play a pivotal role.", keywords = "Animal African trypanosomiasis, Cerebral trypanosomiasis, Disease severity, Immunopathology, Sequestration, Trypanosoma congolense", author = "Pereira, {Sara Silva} and Niz, {Mariana de} and Karine Serre and Marie Ouarn{\'e} and Joana Coelho and Franco, {Cl{\'a}udio A.} and Figueiredo, {Lu{\'i}sa M.}", note = "Funding Information: We thank Dr {\'A}lvaro Acosta-Serrano, at the Liverpool School of Tropical Medicine, and Dr Lo{\"i}c Rivi{\`e}re for providing T. congolense 1/148 and IL3000 parasite lines, respectively. We thank the Silva-Santos lab for the providing the RAG2 KO mice. We are grateful to Dr Margarida Vig{\'a}rio for careful reading of the manuscript. We thank the Rodent, Bioimaging, and Flow Cytometry facilities and the Comparative Pathology Unit (including previous members Pedro Ruivo, DMV and Dr T{\^a}nia Carvalho, DMV) at iMM. This work was supported by European Union's Horizon 2020 research and innovation program through a Marie Sk{\l}odowska-Curie Individual Standard European Fellowship to S.S.P., under grant agreement no. 839960, and from the European Research Council (ERC) (FatTryp, ref. 771714) to L.M.F.. M.D.N. was funded by Human Frontiers LT000047/2019-L (HFSP) and EMBO (ALTF 1048-2016). L.M.F., K.S., and C.A.F. are Investigators CEEC of the Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (CEECIND/03322/2018, CEECIND/00697/2018, CEECIND/04251/2017, respectively). C.A.F. was supported by a European Research Council starting grant (679368), the Fondation Leducq (17CVD03), and the Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (grants IF/00412/2012, EXPL/BEX-BCM/2258/2013, PRECISE-LISBOA-01-0145-FEDER-016394, PTDC/MED-PAT/31639/2017, PTDC/BIA-CEL/32180/2017). Funding Information: We thank Dr {\'A}lvaro Acosta-Serrano, at the Liverpool School of Tropical Medicine, and Dr Lo{\"i}c Rivi{\`e}re for providing T. congolense 1/148 and IL3000 parasite lines, respectively. We thank the Silva-Santos lab for the providing the RAG2 KO mice. We are grateful to Dr Margarida Vig{\'a}rio for careful reading of the manuscript. We thank the Rodent, Bioimaging, and Flow Cytometry facilities and the Comparative Pathology Unit (including previous members Pedro Ruivo, DMV and Dr T{\^a}nia Carvalho, DMV) at iMM. This work was supported by European Union's Horizon 2020 research and innovation program through a Marie Sk{\l}odowska-Curie Individual Standard European Fellowship to S.S.P., under grant agreement no. 839960, and from the European Research Council (ERC) (FatTryp, ref. 771714) to L.M.F.. M.D.N. was funded by Human Frontiers LT000047/2019-L (HFSP) and EMBO (ALTF 1048-2016). L.M.F., K.S., and C.A.F. are Investigators CEEC of the Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (CEECIND/03322/2018, CEECIND/00697/2018, CEECIND/04251/2017, respectively). C.A.F. was supported by a European Research Council starting grant (679368), the Fondation Leducq (17CVD03), and the Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (grants IF/00412/2012, EXPL/BEX- BCM/2258/2013, PRECISE1119 LISBOA-01-0145-FEDER-016394, PTDC/MED-PAT/31639/2017, PTDC/BIA1120 CEL/32180/2017). Publisher Copyright: {\textcopyright} 2022, eLife Sciences Publications Ltd. All rights reserved.", year = "2022", month = jul, doi = "10.7554/elife.77440", language = "English", volume = "11", journal = "eLife", issn = "2050-084X", publisher = "eLife Sciences Publications", } . eLife.
Paving the way @article{2c9d334581ed4d9b87cdfc4e2b79a8b9, title = "Paving the way: contributions of big data to apicomplexan and kinetoplastid research", abstract = "In the age of big data an important question is how to ensure we make the most out of the resources we generate. In this review, we discuss the major methods used in Apicomplexan and Kinetoplastid research to produce big datasets and advance our understanding of Plasmodium, Toxoplasma, Cryptosporidium, Trypanosoma and Leishmania biology. We debate the benefits and limitations of the current technologies, and propose future advancements that may be key to improving our use of these techniques. Finally, we consider the difficulties the field faces when trying to make the most of the abundance of data that has already been, and will continue to be, generated.", keywords = "Apicomplexa, Functional screens, Genomics, Kinetoplastid, Microscopy, Proteomics, Transcriptomics", author = "Kent, {Robyn S.} and Briggs, {Emma M.} and Colon, {Beatrice L.} and Catalina Alvarez and Pereira, {Sara Silva} and {De Niz}, Mariana", note = "Funding Information: We thank both reviewers whose comments improved our work. We thank also our various funders: RSK is funded by the American Heart Association Postdoctoral Fellowship (grant no. 20POST35220017) and U.S. Public Health Service (grant no. AI 139201). EMB is funded by the Wellcome Trust (grant no. 218648/Z/19/Z). SSP is funded by Marie Sk{\l}odowska-Curie Individual Standard European Fellowship (grant no. 839960) and Funda{\c c}{\~a}o Bial (Project 7/2021). MDN is funded by Human Frontier Science Individual Fellowship (grant LT000047/2019-L). Publisher Copyright: Copyright {\textcopyright} 2022 Kent, Briggs, Colon, Alvarez, Silva Pereira and De Niz.", year = "2022", month = jun, day = "6", doi = "10.3389/fcimb.2022.900878", language = "English", volume = "12", journal = "Frontiers in Cellular and Infection Microbiology", issn = "2235-2988", publisher = "Frontiers Media S.A.", } . Frontiers in Cellular and Infection Microbiology.
N 6-methyladenosine in poly(A) tails stabilize VSG transcripts @article{13194662781645cb9e62afe7507113ba, title = "N 6-methyladenosine in poly(A) tails stabilize VSG transcripts", abstract = "RNA modifications are important regulators of gene expression1. In Trypanosoma brucei, transcription is polycistronic and thus most regulation happens post-transcriptionally2. N6-methyladenosine (m6A) has been detected in this parasite, but its function remains unknown3. Here we found that m6A is enriched in 342 transcripts using RNA immunoprecipitation, with an enrichment in transcripts encoding variant surface glycoproteins (VSGs). Approximately 50% of the m6A is located in the poly(A) tail of the actively expressed VSG transcripts. m6A residues are removed from the VSG poly(A) tail before deadenylation and mRNA degradation. Computational analysis revealed an association between m6A in the poly(A) tail and a 16-mer motif in the 3′ untranslated region of VSG genes. Using genetic tools, we show that the 16-mer motif acts as a cis-acting motif that is required for inclusion of m6A in the poly(A) tail. Removal of this motif from the 3′ untranslated region of VSG genes results in poly(A) tails lacking m6A, rapid deadenylation and mRNA degradation. To our knowledge, this is the first identification of an RNA modification in the poly(A) tail of any eukaryote, uncovering a post-transcriptional mechanism of gene regulation.", keywords = "3' Untranslated Regions/genetics, Adenosine/analogs & derivatives, Gene Expression Regulation, RNA/metabolism, RNA Processing, Post-Transcriptional, RNA, Messenger/genetics, Transcription, Genetic, Trypanosoma brucei brucei/genetics, Variant Surface Glycoproteins, Trypanosoma/genetics", author = "Viegas, {Id{\'a}lio J.} and {de Macedo}, {Juan Pereira} and L{\'u}cia Serra and {De Niz}, Mariana and Adriana Tempor{\~a}o and Pereira, {Sara Silva} and Mirza, {Aashiq H.} and Ed Bergstrom and Rodrigues, {Jo{\~a}o A.} and Francisco Aresta-Branco and Jaffrey, {Samie R.} and Figueiredo, {Luisa M.}", note = "Funding Information: We are grateful to support from the Howard Hughes Medical Institute International Early Career Scientist Program (55007419), a European Molecular Biology Organization Installation grant (2151) and La Caixa Foundation (HR20-00361). This work was also partially supported by the ONEIDA project (LISBOA-01-0145-FEDER-016417) co-funded by Fundos Europeus Estruturais e de Investimento (FEEI) from {\textquoteleft}Programa Operacional Regional Lisboa 2020{\textquoteright} and by national funds from Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (FCT). S.R.J. was supported by NIH (R35 NS111631). Researchers were funded by individual fellowships from FCT (PD/BD/105838/2014 to I.J.V., 2020.06827.BD to L.S., SFRH/BD/80718/2011 to F.A.-B., PD/BD/138891/2018 to A.T. and CEECIND/03322/2018 to L.M.F.); a Novartis Foundation for Biomedical-Biological research to J.P.d.M.; a Human Frontier Science Programme long-term postdoctoral fellowship to M.D.N. (LT000047/2019); a Marie Sk{\l}odowska-Curie Individual Standard European Fellowship to S.S.P. (grant no. 839960); the GlycoPar Marie Curie Initial Training Network (GA 608295) to J.A.R. We thank J. Thomas-Oates (University of York, Centre of Excellence in Mass Spectrometry, Department of Chemistry) for the mass spectrometry analysis. The York Centre of Excellence in Mass Spectrometry was created thanks to a major capital investment through Science City York, supported by Yorkshire Forward with funds from the Northern Way Initiative, and subsequent support from EPSRC (EP/K039660/1 and EP/M028127/1). We also thank A. Temudo, A. Nascimento and A. Lima for bioimaging assistance; the laboratories of A. Tom{\'a}s and J. Kelly for providing RNA from Leishmania and T. cruzi, respectively; and A. Pena and members of the Figueiredo and Jaffrey laboratories for helpful discussions. Funding Information: We are grateful to support from the Howard Hughes Medical Institute International Early Career Scientist Program (55007419), a European Molecular Biology Organization Installation grant (2151) and La Caixa Foundation (HR20-00361). This work was also partially supported by the ONEIDA project (LISBOA-01-0145-FEDER-016417) co-funded by Fundos Europeus Estruturais e de Investimento (FEEI) from ?Programa Operacional Regional Lisboa 2020? and by national funds from Funda??o para a Ci?ncia e a Tecnologia (FCT).?S.R.J. was supported by NIH (R35 NS111631). Researchers were funded by individual fellowships from FCT (PD/BD/105838/2014 to I.J.V., 2020.06827.BD to L.S., SFRH/BD/80718/2011 to F.A.-B.,?PD/BD/138891/2018 to A.T. and CEECIND/03322/2018 to L.M.F.); a Novartis Foundation for Biomedical-Biological research to J.P.d.M.; a Human Frontier Science Programme long-term postdoctoral fellowship to M.D.N. (LT000047/2019); a Marie Sk?odowska-Curie Individual Standard European Fellowship to S.S.P. (grant no. 839960); the GlycoPar Marie Curie Initial Training Network (GA 608295) to J.A.R. We thank J. Thomas-Oates (University of York, Centre of Excellence in Mass Spectrometry, Department of Chemistry) for the mass spectrometry analysis. The York Centre of Excellence in Mass Spectrometry was created thanks to a major capital investment through Science City York, supported by Yorkshire Forward with funds from the Northern Way Initiative, and subsequent support from EPSRC (EP/K039660/1 and EP/M028127/1). We also thank A. Temudo, A. Nascimento and A. Lima for bioimaging assistance; the laboratories of A. Tom?s and J. Kelly for providing RNA from Leishmania and T. cruzi , respectively; and A. Pena and members of the Figueiredo and Jaffrey laboratories for helpful discussions. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.", year = "2022", month = apr, day = "14", doi = "10.1038/s41586-022-04544-0", language = "English", volume = "604", pages = "362--370", journal = "Nature", issn = "1476-4687", publisher = "Nature Publishing Group", number = "7905", } . Nature.
N6-methyladenosine in poly(A) tails stabilize VSG transcripts @article { author = {Idálio Viegas and Juan Pereira de Macedo and Serra, Lúcia and Mariana De Niz and Adriana Temporão and SILVA PEREIRA, SARA and A Mirza and et al. Autor correspondente: Figueiredo, Luisa M..}, title = {N6-methyladenosine in poly(A) tails stabilize VSG transcripts }, journal = {Nature}, year = {2022}, month = {mar} }. Nature.
Evolution of the variant surface glycoprotein family in African trypanosomes @article{d127b4fc16144684ab01b3656595764f, title = "Evolution of the variant surface glycoprotein family in African trypanosomes", abstract = "An intriguing and remarkable feature of African trypanosomes is their antigenic variation system, mediated by the variant surface glycoprotein (VSG) family and fundamental to both immune evasion and disease epidemiology within host populations. Recent studies have revealed that the VSG repertoire has a complex evolutionary history. Sequence diversity, genomic organization, and expression patterns are species-specific, which may explain other variations in parasite virulence and disease pathology. Evidence also shows that we may be underestimating the extent to what VSGs are repurposed beyond their roles as variant antigens, establishing a need to examine VSG functionality more deeply. Here, we review sequence variation within the VSG gene family, and highlight the many opportunities to explore their likely diverse contributions to parasite survival.", keywords = "African trypanosomes, African trypanosomiasis, Antigenic diversity, Antigenic variation, Nagana, Variant surface glycoproteins", author = "Pereira, {Sara Silva} and Jackson, {Andrew P.} and Figueiredo, {Lu{\'i}sa M.}", note = "Publisher Copyright: {\textcopyright} 2021 The Authors", year = "2022", month = jan, doi = "10.1016/j.pt.2021.07.012", language = "English", volume = "38", pages = "23--36", journal = "Trends in Parasitology", issn = "1471-4922", publisher = "Elsevier Ltd.", number = "1", } . Trends in Parasitology.
Sara Silva Pereira and Andrew P. Jackson and Lu{\'{\i}}sa M. Figueiredo(2021). Evolution of the variant surface glycoprotein family in African trypanosomes . Trends in Parasitology. Elsevier {BV}
Variant antigen diversity in Trypanosoma vivax is not driven by recombination @article{17c97469d16147f5abb023d10dd70221, title = "Variant antigen diversity in Trypanosoma vivax is not driven by recombination", abstract = "African trypanosomes (Trypanosoma) are vector-borne haemoparasites that survive in the vertebrate bloodstream through antigenic variation of their Variant Surface Glycoprotein (VSG). Recombination, or rather segmented gene conversion, is fundamental in Trypanosoma brucei for both VSG gene switching and for generating antigenic diversity during infections. Trypanosoma vivax is a related, livestock pathogen whose VSG lack structures that facilitate gene conversion in T. brucei and mechanisms underlying its antigenic diversity are poorly understood. Here we show that species-wide VSG repertoire is broadly conserved across diverse T. vivax clinical strains and has limited antigenic repertoire. We use variant antigen profiling, coalescent approaches and experimental infections to show that recombination plays little role in diversifying T. vivax VSG sequences. These results have immediate consequences for both the current mechanistic model of antigenic variation in African trypanosomes and species differences in virulence and transmission, requiring reconsideration of the wider epidemiology of animal African trypanosomiasis.", keywords = "Antigenic Variation/genetics, DNA, Protozoan, Evolution, Molecular, Genome, Protozoan, Host-Parasite Interactions/immunology, Immune evasion, Phylogeny, Protozoan Proteins/genetics, Recombination, Genetic/genetics, Sequence homology, Species specificity, Transcriptome, Trypanosoma brucei brucei/genetics, Trypanosoma vivax/genetics, Trypanosomiasis, African/immunology, Variant Surface Glycoproteins, Trypanosoma/genetics", author = "Pereira, {Sara Silva} and {de Almeida Castilho Neto}, {Kayo J.G.} and Duffy, {Craig W.} and Peter Richards and Harry Noyes and Moses Ogugo and {Rog{\'e}rio Andr{\'e}}, Marcos and Zakaria Bengaly and Steve Kemp and Teixeira, {Marta M.G.} and Machado, {Rosangela Z.} and Jackson, {Andrew P.}", note = "Funding Information: This work was supported by grants from the Biotechnology and Biological Sciences Research Council (BB/M022811/1 and BB/R021139/1), an International Veterinary Vaccinology Network (IVVN) pump-priming award, a Bill and Melinda Gates Foundation Grand Challenges Explorations award (Round 11), and the Wellcome Trust (WT206815/Z/17/Z). Publisher Copyright: {\textcopyright} 2020, The Author(s).", year = "2020", month = dec, day = "1", doi = "10.1038/s41467-020-14575-8", language = "English", volume = "11", journal = "Nature Communications", issn = "2041-1723", publisher = "Nature Publishing Group", number = "1", } . Nature Communications.
VAPPER @article{629c665e56544ab3a444e87de4e1e020, title = "VAPPER: high-throughput variant antigen profiling in African trypanosomes of livestock", abstract = "Background: Analysing variant antigen gene families on a population scale is a difficult challenge for conventional methods of read mapping and variant calling due to the great variability in sequence, copy number, and genomic loci. In African trypanosomes, hemoparasites of humans and animals, this is complicated by variant antigen repertoires containing hundreds of genes subject to various degrees of sequence recombination. Findings: We introduce Variant Antigen Profiler (VAPPER), a tool that allows automated analysis of the variant surface glycoprotein repertoires of the most prevalent livestock African trypanosomes. VAPPER produces variant antigen profiles for any isolate of the veterinary pathogens Trypanosoma congolense and Trypanosoma vivax from genomic and transcriptomic sequencing data and delivers publication-ready figures that show how the queried isolate compares with a database of existing strains. VAPPER is implemented in Python. It can be installed to a local Galaxy instance from the ToolShed (https://toolshed.g2.bx.psu.edu/) or locally on a Linux platform via the command line (https://github.com/PGB-LIV/VAPPER). The documentation, requirements, examples, and test data are provided in the Github repository. Conclusion: By establishing two different, yet comparable methodologies, our approach is the first to allow large-scale analysis of African trypanosome variant antigens, large multi-copy gene families that are otherwise refractory to high-throughput analysis.", keywords = "African trypanosomes, VAPPER, Variant antigen profiling, Variant surface glycoproteins", author = "Pereira, {Sara Silva} and John Heap and Jones, {Andrew R.} and Jackson, {Andrew P.}", note = "Funding Information: This work was supported by a Grand Challenges (Round 11) award fromthe Bill and Melinda Gates Foundation, a BBSRC New investigator Award (BB/M022811/1), and the Technology Directorate of the University of Liverpool to A.P.J. Funding Information: This work was supported by a Grand Challenges (Round 11) award from the Bill and Melinda Gates Foundation, a BBSRC New investigator Award (BB/M022811/1), and the Technology Directorate of the University of Liverpool to A.P.J. Publisher Copyright: {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press.", year = "2019", month = sep, day = "18", doi = "10.1093/gigascience/giz091", language = "English", volume = "8", journal = "GigaScience", issn = "2047-217X", publisher = "Oxford University Press", number = "9", } . GigaScience.
Silva Pereira S, Heap J, Jones AR, Jackson AP(2019). VAPPER: High-throughput variant antigen profiling in African trypanosomes of livestock . GigaScience.
Tissue tropism in parasitic diseases @article{66e02daf16864a5392bb820e4fe61c31, title = "Tissue tropism in parasitic diseases", abstract = "Parasitic diseases, such as sleeping sickness, Chagas disease and malaria, remain a major cause of morbidity and mortality worldwide, but particularly in tropical, developing countries. Controlling these diseases requires a better understanding of host–parasite interactions, including a deep appreciation of parasite distribution in the host. The preferred accumulation of parasites in some tissues of the host has been known for many years, but recent technical advances have allowed a more systematic analysis and quantifications of such tissue tropisms. The functional consequences of tissue tropism remain poorly studied, although it has been associated with important aspects of disease, including transmission enhancement, treatment failure, relapse and clinical outcome. Here, we discuss current knowledge of tissue tropism in Trypanosoma infections in mammals, describe potential mechanisms of tissue entry, comparatively discuss relevant findings from other parasitology fields where tissue tropism has been extensively investigated, and reflect on new questions raised by recent discoveries and their potential impact on clinical treatment and disease control strategies.", keywords = "Nagana, Parasites, Sleeping sickness, Tissue tropism, Trypanosomes", author = "Pereira, {Sara Silva} and Sandra Trindade and {De Niz}, Mariana and Figueiredo, {Luisa M.}", note = "Publisher Copyright: {\textcopyright} 2019 The Authors.", year = "2019", month = may, day = "1", doi = "10.1098/rsob.190036", language = "English", volume = "9", journal = "Open biology", issn = "2046-2441", publisher = "The Royal Society", number = "5", } . Open biology.
Transcriptome, proteome and draft genome of Euglena gracilis @article{ae93d354fd304c68a01f40d73f270883, title = "Transcriptome, proteome and draft genome of Euglena gracilis", abstract = "Background: Photosynthetic euglenids are major contributors to fresh water ecosystems. Euglena gracilis in particular has noted metabolic flexibility, reflected by an ability to thrive in a range of harsh environments. E. gracilis has been a popular model organism and of considerable biotechnological interest, but the absence of a gene catalogue has hampered both basic research and translational efforts. Results: We report a detailed transcriptome and partial genome for E. gracilis Z1. The nuclear genome is estimated to be around 500 Mb in size, and the transcriptome encodes over 36,000 proteins and the genome possesses less than 1% coding sequence. Annotation of coding sequences indicates a highly sophisticated endomembrane system, RNA processing mechanisms and nuclear genome contributions from several photosynthetic lineages. Multiple gene families, including likely signal transduction components, have been massively expanded. Alterations in protein abundance are controlled post-transcriptionally between light and dark conditions, surprisingly similar to trypanosomatids. Conclusions: Our data provide evidence that a range of photosynthetic eukaryotes contributed to the Euglena nuclear genome, evidence in support of the 'shopping bag' hypothesis for plastid acquisition. We also suggest that euglenids possess unique regulatory mechanisms for achieving extreme adaptability, through mechanisms of paralog expansion and gene acquisition.", keywords = "Cellular evolution, Euglena gracilis, Excavata, Gene architecture, Horizontal gene transfer, Plastid, Secondary endosymbiosis, Splicing, Transcriptome", author = "Ebenezer, {Thankgod E.} and Martin Zoltner and Alana Burrell and Anna Nenarokova and {Nov{\'a}k Vanclov{\'a}}, {Anna M.G.} and Binod Prasad and Petr Soukal and Carlos Santana-Molina and Ellis O'Neill and Nankissoor, {Nerissa N.} and Nithya Vadakedath and Viktor Daiker and Samson Obado and Sara Silva-Pereira and Jackson, {Andrew P.} and Devos, {Damien P.} and Julius Luke{\v s} and Michael Lebert and Sue Vaughan and Vladim{\'i}r Hampl and Mark Carrington and Ginger, {Michael L.} and Dacks, {Joel B.} and Steven Kelly and Field, {Mark C.}", note = "Funding Information: This work was supported by the Yousef Jameel Academic Program (through the Yousef Jameel PhD Scholarship), the Cambridge Commonwealth, European and International Trust, the Cambridge University Student Registry, the Cambridge Philosophical Society (all to TEE), the Medical Research Council (Grant #: P009018/1 to MCF), and German Aerospace Center - DLR, Cologne, on the behalf of Federal Ministry of Education and Research (BMBF), Germany (Grant no: 50WB1128 and 50WB1528 to ML), the European Research Council CZ LL1601 BFU2013-40866-P (to DPD) and the Czech Ministry of Education, Youth and Sports - National Sustainability Program II (Project BIOCEV-FAR) LQ 1604, by the project BIOCEV (CZ.1.05/1.1.00/02.0109), by the Centre for research of pathogenicity and virulence of parasites CZ.02.1.01/0.0/0.0/16_019/0000759 and by the Czech Science Foundation project nr. 16-25280S (to VH, AV and PS). Publisher Copyright: {\textcopyright} 2019 The Author(s).", year = "2019", month = feb, day = "7", doi = "10.1186/s12915-019-0626-8", language = "English", volume = "17", journal = "BMC Biology", issn = "1741-7007", publisher = "BioMed Central Ltd.", number = "1", } . BMC Biology.
The structure of a conserved telomeric region associated with variant antigen loci in the blood parasite trypanosoma congolense @article{19434b68c5c44a159300b78213cb656a, title = "The structure of a conserved telomeric region associated with variant antigen loci in the blood parasite trypanosoma congolense", abstract = "African trypanosomiasis is a vector-borne disease of humans and livestock caused by African trypanosomes (Trypanosoma spp.). Survival in the vertebrate bloodstream depends on antigenic variation of Variant Surface Glycoproteins (VSGs) coating the parasite surface. In T. brucei, a model for antigenic variation, monoallelic VSG expression originates from dedicated VSG expression sites (VES). Trypanosoma brucei VES have a conserved structure consisting of a telomeric VSG locus downstream of unique, repeat sequences, and an independent promoter. Additional protein-coding sequences, known as {"}Expression Site Associated Genes (ESAGs){"}, are also often present and are implicated in diverse, bloodstream-stage functions. Trypanosoma congolense is a related veterinary pathogen, also displaying VSG-mediated antigenic variation. A T. congolense VES has not been described, making it unclear if regulation of VSG expression is conserved between species. Here, we describe a conserved telomeric region associated with VSG loci from long-read DNA sequencing of two T. congolense strains, which consists of a distal repeat, conserved noncoding elements and other genes besides the VSG; although these are not orthologous to T. brucei ESAGs. Most conserved telomeric regions are associated with accessory minichromosomes, but the same structure may also be associated with megabase chromosomes. We propose that this region represents the T. congolense VES, and through comparison with T. brucei, we discuss the parallel evolution of antigenic switching mechanisms, and unique adaptation of the T. brucei VES for developmental regulation of bloodstream-stage genes. Hence, we provide a basis for understanding antigenic switching in T. congolense and the origins of the African trypanosome VES.", keywords = "Antigenic variation, ESAG, Expression site, Telomere, Trypanosoma congolense, Variant surface glycoprotein", author = "Abbas, {Ali Hadi} and Pereira, {Sara Silva} and Simon D'Archivio and Bill Wickstead and Morrison, {Liam J.} and Neil Hall and Christiane Hertz-Fowler and Darby, {Alistair C.} and Jackson, {Andrew P.}", note = "Funding Information: We would like to thank Dr Jane Munday (University of Glasgow) for preparation of the T. congolense IL3000 DNA. A.H.A. would like to acknowledge the Iraqi Ministry of Higher Education and Scientific Research/University of Kufa/Faculty of Veterinary Medicine for funding part of this research. This work was supported by a Grand Challenges (Round 11) award from the Bill and Melinda Gates Foundation and a Biotechnology and Biological Sciences Research Council (BBSRC) New investigator Award (BB/M022811/1) to A.P.J.; by Iraqi Ministry of Higher Education and Scientific Research/ Iraqi Cultural Attach{\'e}{\textquoteright} Award (977) awarded to A.C.D. and A.H.A.; and by BBSRC New Investigator Award (BB/ J01477X/1) to B.W. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} The Author(s) 2018.", year = "2018", month = sep, day = "1", doi = "10.1093/gbe/evy186", language = "English", volume = "10", pages = "2458--2473", journal = "Genome Biology and Evolution", issn = "1759-6653", publisher = "Oxford University Press", number = "9", } . Genome Biology and Evolution.
Variant antigen repertoires in Trypanosoma congolense populations and experimental infections can be profiled from deep sequence data using universal protein motifs @article{cc086b0059c846dfa878224590048357, title = "Variant antigen repertoires in Trypanosoma congolense populations and experimental infections can be profiled from deep sequence data using universal protein motifs", abstract = "African trypanosomes are vector-borne hemoparasites of humans and animals. In the mammal, parasites evade the immune response through antigenic variation. Periodic switching of the variant surface glycoprotein (VSG) coat covering their cell surface allows sequential expansion of serologically distinct parasite clones. Trypanosome genomes contain many hundreds of VSG genes, subject to rapid changes in nucleotide sequence, copy number, and chromosomal position. Thus, analyzing, or even quantifying, VSG diversity over space and time presents an enormous challenge to conventional techniques. Indeed, previous population genomic studies have overlooked this vital aspect of pathogen biology for lack of analytical tools. Here we present a method for analyzing population-scale VSG diversity in Trypanosoma congolense from deep sequencing data. Previously, we suggested that T. congolense VSGs segregate into defined “phylotypes” that do not recombine. In our data set comprising 41 T. congolense genome sequences from across Africa, these phylotypes are universal and exhaustive. Screening sequence contigs with diagnostic protein motifs accurately quantifies relative phylotype frequencies, providing a metric of VSG diversity, called the “variant antigen profile.” We applied our metric to VSG expression in the tsetse fly, showing that certain, rare VSG phylotypes may be preferentially expressed in infective, metacyclic-stage parasites. Hence, variant antigen profiling accurately and rapidly determines the T. congolense VSG gene and transcript repertoire from sequence data, without need for manual curation or highly contiguous sequences. It offers a tractable approach to measuring VSG diversity across strains and during infections, which is imperative to understanding the host–parasite interaction at population and individual scales.", keywords = "Amino Acid Motifs, Animals, Male, Polymorphism, Genetic, Sequence Analysis, DNA/methods, Trypanosoma congolense/genetics, Tsetse Flies/parasitology, Variant Surface Glycoproteins, Trypanosoma/chemistry", author = "Pereira, {Sara Silva} and Aitor Casas-S{\'a}nchez and Haines, {Lee R.} and Moses Ogugo and Kihara Absolomon and Mandy Sanders and Steve Kemp and {\'A}lvaro Acosta-Serrano and Harry Noyes and Matthew Berriman and Jackson, {Andrew P.}", note = "Funding Information: (Liverpool School of Tropical Medicine) for tsetse fly rearing. This work was supported by the Biotechnology and Biological Sciences Research Council (BB/M022811/1), the Bill and Melinda Gates Foundation Grand Challenges Explorations Round 11, the GlycoPar-EU FP7 Marie Curie Initial Training Network (GA 608295), and the Wellcome Trust (WT098051). Funding Information: We thank Pegine Walrad (University of York) for the T. congolense 1/148-infected mouse blood stabilates and Dan Southern (Liverpool School of Tropical Medicine) for tsetse fly rearing. This work was supported by the Biotechnology and Biological Sciences Research Council (BB/M022811/1), the Bill and Melinda Gates Foundation Grand Challenges Explorations Round 11, the GlycoPar-EU FP7 Marie Curie Initial Training Network (GA 608295), and the Wellcome Trust (WT098051). Publisher Copyright: {\textcopyright} 2018 Silva Pereira et al.", year = "2018", month = sep, doi = "10.1101/gr.234146.118", language = "English", volume = "28", pages = "1383--1394", journal = "Genome Research", issn = "1088-9051", publisher = "Cold Spring Harbor Laboratory Press", number = "9", } . Genome Research.
Silva Pereira S, Casas-Sánchez A, Haines LR, Ogugo M, Absolomon K, Sanders M, Kemp S, Acosta-Serrano Á, Noyes H, Berriman M, et al.(2018). Variant antigen repertoires in Trypanosoma congolense populations and experimental infections can be profiled from deep sequence data using universal protein motifs . Genome research.
UDP-glycosyltransferase genes in trypanosomatid genomes have diversified independently to meet the distinct developmental needs of parasite adaptations @article{74111ecb23c8484abab7d46fbd02ba94, title = "UDP-glycosyltransferase genes in trypanosomatid genomes have diversified independently to meet the distinct developmental needs of parasite adaptations", abstract = "Background: Trypanosomatid parasites such as Trypanosoma spp. and Leishmania spp. are a major source of infectious disease in humans and domestic animals worldwide. Fundamental to the host-parasite interactions of these potent pathogens are their cell surfaces, which are highly decorated with glycosylated proteins and other macromolecules. Trypanosomatid genomes contain large multi-copy gene families encoding UDP-dependent glycosyltransferases (UGTs), the primary role of which is cell-surface decoration. Here we report a phylogenetic analysis of UGTs from diverse trypanosomatid genomes, the aim of which was to understand the origin and evolution of their diversity. Results: By combining phylogenetics with analyses of recombination, and selection, we compared UGT repertoire, genomic context and sequence evolution across 19 trypanosomatids. We identified a UGT lineage present in stercorarian trypanosomes and a free-living kinetoplastid Bodo saltans that likely represents the ancestral state of this gene family. The phylogeny of parasite-specific genes shows that UGTs repertoire in Leishmaniinae and salivarian trypanosomes has expanded independently and with distinct evolutionary dynamics. In the former, the ancestral UGT repertoire was organised in a tandem array from which sporadic transpositions to telomeric regions occurred, allowing expansion most likely through telomeric exchange. In the latter, the ancestral UGT repertoire was comprised of seven subtelomeric lineages, two of which have greatly expanded potentially by gene transposition between these dynamic regions of the genome. Conclusions: The phylogeny of UGTs confirms that they represent a substantial parasite-specific innovation, which has diversified independently in the distinct trypanosomatid lineages. Nonetheless, developmental regulation has been a strong driver of UGTs diversification in both African trypanosomes and Leishmania.", keywords = "Glycosylation, Trypanosomatids, UDP-glycosyltransferases", author = "{Silva Pereira}, Sara and Jackson, {Andrew P.}", note = "Publisher Copyright: {\textcopyright} 2018 The Author(s).", year = "2018", month = mar, day = "14", doi = "10.1186/s12862-018-1149-6", language = "English", volume = "18", journal = "BMC Evolutionary Biology", issn = "1471-2148", publisher = "BioMed Central Ltd.", number = "1", } . BMC Evolutionary Biology.
Abbas, Ali Hadi and Silva Pereira, Sara and D'Archivio, Simon and Wickstead, Bill and Morrison, Liam J and Hall, Neil and Hertz-Fowler, Christiane and Darby, Alistair C and Jackson, Andrew P(2018). The Structure of a Conserved Telomeric Region Associated with Variant Antigen Loci in the Blood Parasite Trypanosoma congolense . Genome Biology and Evolution. 10. (9). p. 2458-2473.
IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test @article{de8437e74a7a44a39002d5b3ce4d3d49, title = "IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test", abstract = "BACKGROUND: Visceral leishmaniasis (VL), caused by protozoa of the Leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic VL is usually fatal. Distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hampered by the lack of prognostic biomarkers for use at point of care. METHODOLOGY/PRINCIPAL FINDINGS: All IgG subclass and IgG isotype antibody levels were determined using unpaired serum samples from Indian and Sudanese patients with differing clinical status of VL, which included pre-treatment active VL, post-treatment cured, post-treatment relapsed, and post kala-azar dermal leishmaniasis (PKDL), as well as seropositive (DAT and/or rK39) endemic healthy controls (EHCs) and seronegative EHCs. L. donovani antigen-specific IgG1 levels were significantly elevated in relapsed versus cured VL patients (p<0.0001). Using paired Indian VL sera, consistent with the known IgG1 half-life, IgG1 levels had not decreased significantly at day 30 after the start of treatment (p = 0.8304), but were dramatically decreased by 6 months compared to day 0 (p = 0.0032) or day 15 (p<0.0001) after start of treatment. Similarly, Sudanese sera taken soon after treatment did not show a significant change in the IgG1 levels (p = 0.3939). Two prototype lateral flow immunochromatographic rapid diagnostic tests (RDTs) were developed to detect IgG1 levels following VL treatment: more than 80% of the relapsed VL patients were IgG1 positive; at least 80% of the cured VL patients were IgG1 negative (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Six months after treatment of active VL, elevated levels of specific IgG1 were associated with treatment failure and relapse, whereas no IgG1 or low levels were detected in cured VL patients. A lateral flow RDT was successfully developed to detect anti-Leishmania IgG1 as a potential biomarker of post-chemotherapeutic relapse.", keywords = "Antibodies, Protozoan/blood, Biomarkers, Chromatography, Affinity, Diagnostic Tests, Routine, Humans, Immunoglobulin G/blood, Leishmania donovani/immunology, Leishmaniasis, Visceral/diagnosis, Recurrence", author = "Tapan Bhattacharyya and Armon Ayandeh and Falconar, {Andrew K} and Shyam Sundar and Sayda El-Safi and Gripenberg, {Marissa A} and Bowes, {Duncan E} and Caroline Thunissen and Singh, {Om Prakash} and Rajiv Kumar and Osman Ahmed and Osama Eisa and Alfarazdeg Saad and Pereira, {Sara Silva} and Marleen Boelaert and Pascal Mertens and Miles, {Michael A}", note = "Publisher Copyright: {\textcopyright} 2014 Bhattacharyya et al.", year = "2014", month = oct, doi = "10.1371/journal.pntd.0003273", language = "English", volume = "8", pages = "1--11", journal = "PLoS Neglected Tropical Diseases", issn = "1935-2727", publisher = "Public Library of Science", number = "10", } . PLoS Neglected Tropical Diseases.
Bhattacharyya T, Ayandeh A, Falconar AK, Sundar S, El-Safi S, Gripenberg MA, Bowes DE, Thunissen C, Singh OP, Kumar R, et al.(2014). IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test . PLoS neglected tropical diseases.
CONFERENCE POSTER
Cytoadhesion of Trypanosoma congolense to bioengineered 3D bovine microvessels @misc { author = {SILVA PEREIRA, SARA and Teresa Porqueddu and Bernabeu, Maria and Figueiredo, Luisa M. and Autor correspondente: SILVA PEREIRA, SARA.}, title = {Cytoadhesion of Trypanosoma congolense to bioengineered 3D bovine microvessels}, year = {2023}, month = {oct} }. EMBO Young Scientists Forum.
Trypanosoma congolense cytoadheres to the brain vasculature @misc { author = {SILVA PEREIRA, SARA and Mariana De Niz and Luísa M Figueiredo}, title = {Trypanosoma congolense cytoadheres to the brain vasculature}, year = {2019}, month = {sep}, keywords = {sequestration; trypanosomes} }. Molecular Parasitology Meeting 2019.
Variant antigen profiling: a novel approach to population genomics of VSG in Trypanosoma congolense @misc { author = {SILVA PEREIRA, SARA}, title = {Variant antigen profiling: a novel approach to population genomics of VSG in Trypanosoma congolense}, year = {2015}, month = {aug} }. 25th International Conference of the World Association for the Advancement of Veterinary Parasitology.
A Bioinformatics Approach to a rapid diagnostic test of visceral leishmaniasis @misc { author = {SILVA PEREIRA, SARA}, title = {A Bioinformatics Approach to a rapid diagnostic test of visceral leishmaniasis}, year = {2013} }. British Society for Parasitology Spring Meeting.
WORKING PAPER
Investigation of Trypanosoma-induced vascular damage sheds insights into Trypanosoma vivax sequestration @techreport{c975e7fde5294121a63046ced545b468, title = "Investigation of Trypanosoma-induced vascular damage sheds insights into Trypanosoma vivax sequestration", abstract = "Multiple blood-borne pathogens infecting mammals establish close interactions with the host vascular endothelium as part of their life cycles. In this work, we investigate differences in the interactions of three Trypanosoma species: T. brucei, T. congolense and T. vivax with the blood vasculature. Infection with these species results in vastly different pathologies, including different effects on vascular homeostasis, such as changes in vascular permeability and microhemorrhages. While all three species are extracellular parasites, T. congolense is strictly intravascular, while T. brucei is capable of surviving both extra- and intravascularly. Our knowledge regarding T. vivax tropism and its capacity of migration across the vascular endothelium is unknown. In this work, we show for the first time that T. vivax parasites sequester to the vascular endothelium of most organs, and that, like T. congolense, T. vivax Y486 is largely incapable of extravasation. Infection with this parasite species results in a unique effect on vascular endothelium receptors including general downregulation of ICAM1 and ESAM, and upregulation of VCAM1, CD36 and E-selectin. Our findings on the differences between the two sequestering species (T. congolense and T. vivax) and the non-sequestering, but extravasating, T. brucei raise important questions on the relevance of sequestration to the parasite{\textquoteright}s survival in the mammalian host, and the evolutionary relevance of both sequestration and extravasation.", author = "Pereira, {Sara Silva} and Daniela Br{\'a}s and Teresa Porqueddu and Nascimento, {Ana M.} and Niz, {Mariana De}", year = "2023", month = sep, day = "18", doi = "10.1101/2023.09.18.558284", language = "English", type = "WorkingPaper", } .
NEWSLETTER ARTICLE