UK:Brazil Joint Centre Partnership in Leishmaniasis (JCPiL)

• Grant number: 18/14398-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: September 01, 2019
• End date: March 31, 2024
• Field of knowledge: Biological Sciences - Parasitology
• Agreement: MRC, UKRI ; Newton Fund, with FAPESP as a partner institution in Brazil
• Principal Investigator: Angela Kaysel Cruz
• Grantee: Angela Kaysel Cruz
• Principal researcher abroad: Jeremy Mottram
• Institution abroad: University of York, England
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais: Dario Simões Zamboni ; Hiro Goto ; Luiz Ricardo Orsini Tosi
• Associated researchers: José Angelo Lauletta Lindoso ; Mírian Nacagami Sotto
• Associated scholarship(s): 23/14086-6 - RuvB-like 1: essentiality and function in Leishmania braziliensis, BP.IC; 23/02228-0 - Evaluation of the role of inflammasomes in Leishmania infantum infection of mice, BP.TT; 21/10043-5 - Comparative computational analyses of transcriptomes and large-scale identification of interactions between RNA-binding proteins and ncRNAs and repair/recombination proteins and DNA, BP.TT; + associated scholarships 20/14059-0 - Protein RuvB-like 1: the biological relevance of putative arginine methylation in Leishmania braziliensis, BP.IC; 20/01883-7 - Does signalling during DNA replication stress drive genome diversity in Leishmania?, BP.PD; 20/00087-2 - Functional validation of potential non-coding RNAs differentially expressed during Leishmania viannia braziliensis life cycle, BP.PD; 20/02372-6 - Actions coordinated by the enzyme Arginine Methyltransferase 5 of Leishmania braziliensis, BP.PD; 20/01323-1 - Evaluation of the role of inflammasomes in Leishmania infantum infection of mice, BP.TT; 20/00088-9 - Epigenetic regulation of Leishmania gene expression, BP.PD; 19/26621-8 - Evaluation of the role of inflammasomas and their signaling pathways in murine experimental infection by Leishmania infantum, BP.PD; 19/18607-5 - Computational identification and structural characterization of non-coding RNA in Leishmania braziliensis, BP.PD; 19/25393-1 - UK:Brazil Joint Centre Partnership in Leishmaniasis (JCPiL). work plan 1 molecular pathology of leishmaniasis: towards host-directed therapy in leishmaniases, BP.PD - associated scholarships

Abstract

Leishmaniasis is a devastating parasitic disease that targets the poorest of society and is the 9th largest global infectious disease burden (WHO). It is truly a Neglected Infectious Disease as the combined financial support of basic and clinical research equates to <2% of infectious disease R&D resources available. Consequently, there are no vaccines available currently and the limited available treatments are repurposed from other applications, have severe side effects; including anaphylaxis, growing drug resistances and are inappropriate for the primarily juvenile leishmaniasis patients. Disease pathologies range from tegumental (mucocutaneous and cutaneous leishmaniasis) to visceral and cases in Brazil alone range from 20,000 TL to 3,500 VL per annum.The UK:Brazil Joint Centre Partnership in leishmaniasis (JCPiL) will fund five inter-related projects and 3 workshops to promote research at the interface of basic and clinical science, to extend existing collaborations between UK and Brazil and to develop new partnerships and interdisciplinary ways of working. Travel will be used to cross train PIs, PDRAs and PhD students in the foremost technologies and expertise available worldwide. Studies will be focused on understanding parasite genetic diversity in the context of variations of Leishmania infectivity and virulence factor expression, mechanisms of immune evasion, diversity of host response, resultant immunopathology and sustained activation that drives chronic disease. We will investigate novel molecular targets of vulnerable pathways that are essential to Leishmania viability, optimise techniques and diagnostic markers to predict and definitively categorize patient pathology profiles to inform more bespoke, effective treatment design. Our JCPiL will create new collaborations in order to build sustainable, fundable future projects and make an impact on this deadly disease. (AU)

Scientific publications

(16)

(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)

OLIVIER, MARTIN; ZAMBONI, DARIO S.. Leishmania Viannia guyanensis, LRV1 virus and extracellular vesicles: a dangerous trio influencing the faith of immune response during muco-cutaneous leishmaniasis. CURRENT OPINION IN IMMUNOLOGY, v. 66, n. SI, p. 108-113, OCT 2020. (13/08216-2, 18/14398-0, 19/11342-6)

REIS, LUIZA C.; RAMOS-SANCHEZ, EDUARDO MILTON; ARAUJO, FERNANDA N.; LEAL, ARIANE F.; OZAKI, CHRISTIANE Y.; SEVILLANO, ORLANDO R.; USCATA, BERNARDINA A.; GOTO, HIRO. Pleiotropic Effect of Hormone Insulin-Like Growth Factor-I in Immune Response and Pathogenesis in Leishmaniases. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2021, MAY 5 2021. (14/08340-8, 19/25393-1, 18/14398-0, 17/02959-4)

SOUZA, MARINA DE ASSIS; RAMOS-SANCHEZ, EDUARDO MILTON; MUXEL, SANDRA MARCIA; LAGOS, DIMITRIS; REIS, LUIZA CAMPOS; PEREIRA, VALERIA REGO ALVES; BRITO, MARIA EDILEUZA FELINTO; ZAMPIERI, RICARDO ANDRADE; KAYE, PAUL MARTIN; FLOETER-WINTER, LUCILE MARIA; et al. miR-548d-3p Alters Parasite Growth and Inflammation in Leishmania (Viannia) braziliensis Infection. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, JUN 10 2021. (18/23512-0, 14/14756-2, 19/25393-1, 18/14398-0, 18/24693-9)

CAMPAGNARO, GUSTAVO D.; NAY, EDWARD; PLEVIN, MICHAEL J.; CRUZ, ANGELA K.; WALRAD, PEGINE B.. Arginine Methyltransferases as Regulators of RNA-Binding Protein Activities in Pathogenic Kinetoplastids. FRONTIERS IN MOLECULAR BIOSCIENCES, v. 8, JUN 11 2021. (18/14398-0, 20/02372-6, 15/13618-8)

ANDRADE, WARRISON A.; ZAMBONI, DARIO S.. NLRC4 biology in immunity and inflammation. Journal of Leukocyte Biology, v. 108, n. 4, p. 11-pg., 2020-06-12. (19/11342-6, 14/04684-4, 13/08216-2, 18/14398-0)

RAMOS-SANCHEZ, EDUARDO MILTON; REIS, LUIZA CAMPOS; SOUZA, MARINA DE ASSIS; MUXEL, SANDRA MARCIA; SANTOS, KAMILA REIS; LAGOS, DIMITRIS; PEREIRA, VALERIA REGO ALVES; DE BRITO, MARIA EDILEUZA FELINTO; KAYE, PAUL MARTIN; FLOETER-WINTER, LUCILE MARIA; et al. miR-548d-3p Is Up-Regulated in Human Visceral Leishmaniasis and Suppresses Parasite Growth in Macrophages. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 14-pg., 2022-02-10. (19/25393-1, 14/14756-2, 18/14398-0, 18/24693-9, 18/23512-0)

LORENZON, LUCAS; QUILLES JR, JOSE C.; CAMPAGNARO, GUSTAVO DANIEL; ORSINE, LISSUR AZEVEDO; ALMEIDA, LETICIA; VERAS, FLAVIO; MISERANI MAGALHAES, RUBENS DANIEL; DINIZ, JULIANA ALCOFORADO; FERREIRA, TIAGO RODRIGUES; CRUZ, ANGELA KAYSEL. Functional Study of Leishmania braziliensis Protein Arginine Methyltransferases (PRMTs) Reveals That PRMT1 and PRMT5 Are Required for Macrophage Infection. ACS INFECTIOUS DISEASES, v. 8, n. 3, p. 17-pg., 2022-03-11. (21/10043-5, 20/00088-9, 16/00969-0, 16/14657-0, 15/13618-8, 18/14398-0, 20/02372-6, 19/18607-5)

CAMPAGNARO, GUSTAVO DANIEL; LORENZON, LUCAS BIGOLIN; RODRIGUES, MATEUS AUGUSTO; DEFINA, TANIA PAULA AQUINO; PINZAN, CAMILA FIGUEIREDO; FERREIRA, TIAGO RODRIGUES; CRUZ, ANGELA KAYSEL. Overexpression of Leishmania major protein arginine methyltransferase 6 reduces parasite infectivity in vivo. Acta Tropica, v. 244, p. 7-pg., 2023-06-01. (15/13618-8, 14/00220-3, 18/14398-0, 13/13237-9, 20/02372-6, 10/01129-9)

OLIVIER, MARTIN; ZAMBONI, DARIO S.. Leishmania Viannia guyanensis, LRV1 virus and extracellular vesicles: a dangerous trio influencing the faith of immune response during muco-cutaneous leishmaniasis. CURRENT OPINION IN IMMUNOLOGY, v. 66, p. 6-pg., 2020-10-01. (13/08216-2, 18/14398-0, 19/11342-6)

ANDRADE, WARRISON A.; ZAMBONI, DARIO S.. NLRC4 biology in immunity and inflammation. Journal of Leukocyte Biology, JUN 2020. (13/08216-2, 18/14398-0, 19/11342-6, 14/04684-4)

DE CARVALHO, RENAN V. H.; LIMA-JUNIOR, DJALMA S.; DE OLIVEIRA, V, CAROLINE; ZAMBONI, DARIO S.. Endosymbiotic RNA virus inhibits Leishmania-induced caspase-11 activation. ISCIENCE, v. 24, n. 1, JAN 22 2021. (19/11342-6, 13/08216-2, 18/14398-0)

DE SA, KEYLA S. G.; AMARAL, LUANA A.; RODRIGUES, TAMARA S.; ISHIMOTO, ADRIENE Y.; DE ANDRADE, WARRISON A. C.; DE ALMEIDA, LETICIA; FREITAS-CASTRO, FELIPE; BATAH, SABRINA S.; OLIVEIRA, SERGIO C.; PASTORELLO, MONICA T.; et al. Gasdermin-D activation promotes NLRP3 activation and host resistance to Leishmania infection. NATURE COMMUNICATIONS, v. 14, n. 1, p. 19-pg., 2023-02-24. (13/08216-2, 18/14398-0, 19/11342-6)

DE CARVALHO, RENAN V. H.; ZAMBONI, DARIO S.. Inflammasome Activation in Response to Intracellular Protozoan Parasites. Trends in Parasitology, v. 36, n. 5, p. 459-472, MAY 2020. (13/08216-2, 18/14398-0, 14/04684-4)

SILVA, GABRIEL L. A.; TOSI, LUIZ R. O.; MCCULLOCH, RICHARD; BLACK, JENNIFER ANN. Unpicking the Roles of DNA Damage Protein Kinases in Trypanosomatids. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 9, AUG 6 2021. (20/01883-7, 18/14398-0, 16/16454-9)

COSTA-SILVA, HELLIDA MARINA; RESENDE, BRUNO CARVALHO; UMAKI, ADRIANA CASTILHOS SOUZA; PRADO, WILLIAN; DA SILVA, MARCELO SANTOS; VIRGILIO, STELA; MACEDO, ANDREA MARA; PENA, SERGIO DANILO JUNHO; TAHARA, ERICH BIRELLI; TOSI, LUIZ RICARDO ORSINI; et al. DNA Topoisomerase 3 alpha Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 9, MAY 13 2021. (14/24170-5, 18/14398-0, 13/07467-1, 16/50050-2)

MENDES-AGUIAR, CAROLINA; LOPES-SIQUEIRA, CAMILLA; PETTITO-ASSIS, FABRICIO; PEREIRA-OLIVEIRA, MARCIA; DE OLIVEIRA-NETO, MANOEL PAES; PIRMEZ, CLAUDE; DA-CRUZ, ALDA MARIA; GOTO, HIRO. Dual Role of Insulin-Like Growth Factor (IGF)-I in American Tegumentary Leishmaniasis. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2021, MAR 30 2021. (18/14398-0)