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Visceral leishmaniasis: genomics approaches for integrated molecular analysis of host and parasite

Grant number: 16/20258-0
Support type:Research Grants - Young Investigators Grants
Duration: July 01, 2017 - April 30, 2023
Field of knowledge:Biological Sciences - Parasitology
Principal researcher:Sandra Regina Costa Maruyama
Grantee:Sandra Regina Costa Maruyama
Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
Assoc. researchers:Anderson Ferreira da Cunha ; Felipe Roberti Teixeira ; Iran Malavazi ; João Santana da Silva
Associated scholarship(s):21/10358-6 - Genomic analysis of Leishmaniinae parasites isolated from human visceral Leishmaniasis, BP.IC
21/06105-5 - Comparative Genomics of Leishmaniinae parasites isolated from human visceral leishmaniasis, BP.MS
20/14011-8 - Phenotypic characterization and genomic analysis of Crithidia-like parasites obtained from patients diagnosed with Visceral Leishmaniasis, BP.DD
+ associated scholarships 19/24764-6 - Tools for nucleic acid manipulation in samples of visceral leishmaniasis, BP.TT
19/07718-0 - Tools for nucleic acid manipulation in samples of visceral leishmaniasis., BP.TT
19/03095-9 - Screening of clinical isolates of Leishmania sp. for genome sequencing, BP.MS
18/26799-9 - Phenotypic characterization and genomic analysis of Crithidia-like parasites obtained from patients diagnosed with visceral leishmaniasis, BP.MS
18/05767-1 - Tools for nucleic acid manipulation in samples of Visceral Leishmaniasis, BP.TT
17/16328-6 - Visceral Leishmaniasis: genomics approaches for integrated molecular analysis of host and parasite., BP.JP - associated scholarships

Abstract

Visceral leishmaniasis (VL) in Brazil is caused by protozoan parasites Leishmania infantum. It is a chronic and disseminated disease that can be potentially fatal if untreated. Interestingly, most people infected are asymptomatic, whereas approximately 15% of L. infantum infections develop clinical manifestations, which range from mild to severe forms of disease. Both host immune responses and the genetics of parasites are crucial to the outcome of infection; however the molecular mechanisms involved in the pathogenesis of VL remain poorly understood. We believe that molecular analyses of leukocytes from asymptomatic individuals (resistants to VL), diseased and cured patients, as well as the genomic analyses of clinical isolates will provide insightful information to elucidate the molecular mechanisms of parasite/host interaction that underlie the outcome of infection. Thus, the aim of this proposal is performing an integrated molecular analysis of VL through the Functional Genomics of host (whole blood RNA-seq) and the Comparative Genomics of parasites (WGS, whole-genome sequencing) for data integration that can be helpful to discovery of novel targets for therapies and drugs. Our preliminary results on RNA-seq analyses of blood leukocytes from VL patients and WGS of Leishmania clinical isolates reveal that this is an innovative and promising research proposal. Through the RNA-seq analyses of symptomatic infected patients before (diseased patients) and after (cured patients) of being submitted to the conventional treatment, asymptomatic patients and healthy control individuals, the gene signatures related to VL will be identified. The dual RNA-seq of patient samples will identify Leishmania transcripts. Also, a protocol for RNA-seq of whole blood stimulation will be developed. Comparative Genomics analyses of clinical isolates will determine ploidy, chromosome somy, copy number variations (CNVs) and single-nucleotide polymorphisms (SNPs) and genes or genomic regions associated to resistance to conventional drugs, beyond the valuable biological information about Brazilian strains of parasites. Finally, according to the purpose of FAPESP Young Investigator Award, this proposal aims to establish a novel research area (Genomics of host/parasite interaction in leishmaniasis) at the Department of Genetics and Evolution of the Federal University of São Carlos. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
Articles published in other media outlets (0 total):
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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MARUYAMA, SANDRA REGINA; ROGERIO, LUANA APARECIDA; FREITAS, PATRICIA DOMINGUES; GERALDES TEIXEIRA, MARTA MARIA; CHAVES RIBEIRO, JOSE MARCOS. Total Ortholog Median Matrix as an alternative unsupervised approach for phylogenomics based on evolutionary distance between protein coding genes. SCIENTIFIC REPORTS, v. 11, n. 1 FEB 15 2021. Web of Science Citations: 0.
MARUYAMA, SANDRA R.; DE SANTANA, ALYNNE K. M.; TAKAMIYA, NAYORE T.; TAKAHASHI, TALITA Y.; ROGERIO, LUANA A.; OLIVEIRA, CAIO A. B.; MILANEZI, CRISTIANE M.; TROMBELA, VIVIANE A.; CRUZ, ANGELA K.; JESUS, AMELIA R.; BARRETO, ALINE S.; DA SILVA, ANGELA M.; ALMEIDA, ROQUE P.; RIBEIRO, JOSE M.; SILVA, JOAO S. Non-Leishmania Parasite in Fatal Visceral Leishmaniasis Like Disease, Brazil. Emerging Infectious Diseases, v. 25, n. 11, p. 2088-2092, NOV 2019. Web of Science Citations: 1.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.