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Centre of Excellence in New Target Discovery

Grant number: 20/13139-0
Support Opportunities:Research Grants - Research Centers in Engineering Program
Duration: October 01, 2021 - September 30, 2026
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Convênio/Acordo: GlaxoSmithKline
Principal Investigator:Ana Marisa Chudzinski-Tavassi
Grantee:Ana Marisa Chudzinski-Tavassi
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Host Companies:Secretaria da Saúde (São Paulo - Estado). Instituto Butantan
Glaxosmithkline Brasil Ltda
City: Rio de JaneiroSão Paulo
Pesquisadores principais:
Denise Vilarinho Tambourgi ; Olga Celia Martinez Ibanez ; Vanessa Olzon Zambelli
Associated researchers:Andrea Borrego ; Carla Cristina Squaiella ; Carlos Deocesano-Pereira ; Catarina de Fatima Pereira Teixeira ; Cristina Maria Fernandes ; Dilza Trevisan Silva ; Giselle Pidde Marques Porto ; Irina Kerkis ; José Ricardo Jensen ; Marcelo Medina de Souza ; Marcus Vinicius Buri ; Miryam Paola Alvarez Flores ; Nancy Starobinas ; Paula Cristiane Pohl ; Vanessa Olzon Zambelli
Associated grant(s):23/01532-8 - Neuroblastoma gene editing by CRISPR/Cas9 for target validation involved in pain and inflammation, AP.R
Associated scholarship(s):23/12791-4 - Functional validation of molecular targets for the treatment of osteoarthritis in a model of chondrocytes treated with Pararama bristle extract, BP.TT
23/13536-8 - Science dissemination and popularization content development, BP.TT
22/16532-0 - Validation of novel molecular targets from anti-inflammatory and cytoprotective molecules in culture cells, BP.PD
22/15071-0 - Implementation of a molecular biology platform for functional genomics by CRISPR/cas9 system, BP.PD
22/01892-1 - New molecular targets identification and validation of anti-inflammatory peptides applying distinct mass spectrometry-based proteomics approaches, BP.PD

Abstract

CENTD's focus is to combine the expertise of researchers at the Butantan Institute (biochemistry, OMICS, molecular and cellular biology, pharmacology, genetics, bioinformatics, immunology, and in vitro and in vivo assays) with GSK's experience in the search and validation of new targets related to immune-inflammatory diseases, to enable the design and development of new therapeutic agents. During the first 5 years, the CENTD team dedicated efforts to the implementation of 6 cell models that allowed the screening (screening) of 32 animal venoms, originating from different places in the world and 18 synthetic peptides, originated through computational analysis, from of proteins. Initially, the inflammatory potential of animal venoms and derived fractions was analyzed by screening in established cell models. Subsequently, the assays were optimized for the identification of anti-inflammatory activity and the samples were analyzed under these conditions. The analysis included high-content screening, multiplex, flow cytometry and mass spectrometry techniques. Transcriptomic, proteomic and bioinformatics analyzes were also performed, generating a very significant database. The screening proved to be effective, since of the 32 poisons analyzed, 3 were chosen for the next stages (target identification and validation). Likewise, of the 18 peptides studied, 5 were chosen for the follow-up of assays that seek to validate targets, using especially new technologies that will be implemented in the next stage. Also, the integration of data from different omic techniques, allowed, from tests with crude poison, the choice of 5 molecular targets for validation in the next step. In terms of disseminating science, several activities were developed by CENTD. Among them, exhibitions held in places of great circulation and visibility, such as subway stations and thermometers located at 300 addresses in São Paulo. According to the media, CENTD images have probably been viewed by more than 2 million people. In addition, entrepreneurial training was also offered by CENTD through the participation of the member group in the MBA - Health Innovation Management, in the organization of short courses and seminars, always focusing on innovation processes. During this period, 5 patents were applied at the INPI / PCT and 34 scientific articles were published. More than 50 masters and doctoral students, supervised by the main researchers (PIs), completed their theses and, more than 20 postdoctoral students, were supervised by the PIs. In addition, there is also the transfer of know-how between the main actors of the GSK project and the research groups coordinated by PIs (main researchers), composed of scientific progress meetings every two months, technical visits by GSK scientists to support the development of CENTD projects and annual visits by the advisory board. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications (6)
(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)
DE MELO, THATIANA CORREA; TREVISAN-SILVA, DILZA; ALVAREZ-FLORES, MIRYAM P.; GOMES, RENATA NASCIMENTO; DE SOUZA, MARCELO MEDINA; VALERIO, HELLEN PAULA; OLIVEIRA, DOUGLAS S.; DEOCESANO-PEREIRA, CARLOS; BOTOSSO, VIVIANE FONGARO; CALIL JORGE, SORAIA ATTIE; et al. Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 18, p. 17-pg., . (20/10847-4, 20/05293-0, 20/13139-0)
APOLINARIO, ALEXSANDRA CONCEICAO; SALATA, GIOVANNA CASSONE; DE SOUZA, MARCELO MEDINA; CHORILLI, MARLUS; LOPES, LUCIANA BIAGINI. Rethinking Breast Cancer Chemoprevention: Technological Advantages and Enhanced Performance of a Nanoethosomal-Based Hydrogel for Topical Administration of Fenretinide. AAPS PHARMSCITECH, v. 23, n. 4, p. 14-pg., . (18/13877-1, 14/50928-2, 20/13139-0, 18/14375-0)
BUFALO, MICHELLE CRISTIANE; DE ALMEIDA, MAIRA ESTANISLAU SOARES; JENSEN, JOSE RICARDO; DEOCESANO-PEREIRA, CARLOS; LICHTENSTEIN, FLAVIO; PICOLO, GISELE; CHUDZINSKI-TAVASSI, ANA MARISA; SAMPAIO, SANDRA COCCUZZO; CURY, YARA; ZAMBELLI, VANESSA OLZON. uman Sensory Neuron-like Cells and Glycated Collagen Matrix as a Model for the Screening of Analgesic Compound. CELLS, v. 11, n. 2, . (15/50040-4, 20/13139-0)
MORAIS, K. L. P.; CICCONE, L.; STURA, E.; ALVAREZ-FLORES, M. P.; MOURIER, G.; DRIESSCHE, M. VANDEN; SCIANI, J. M.; IQBAL, A.; KALIL, S. P.; PEREIRA, G. J.; et al. Structural and functional properties of the Kunitz-type and C-terminal domains of Amblyomin-X supporting its antitumor activity. FRONTIERS IN MOLECULAR BIOSCIENCES, v. 10, p. 16-pg., . (15/50040-4, 20/13139-0, 13/07467-1)
BORREGO, ANDREA; COLOMBO, FRANCESCA; DE SOUZA, JEAN GABRIEL; JENSEN, JOSE RICARDO; DASSANO, ALICE; PIAZZA, ROCCO; RODRIGUES DOS SANTOS, BARBARA ANAIS; RIBEIRO, ORLANDO GARCIA; DE FRANCO, MARCELO; KOURY CABRERA, WAFA HANNA; et al. Pycard and BC017158 Candidate Genes of Irm1 Locus Modulate Inflammasome Activation for IL-1 beta Production. FRONTIERS IN IMMUNOLOGY, v. 13, p. 16-pg., . (17/06736-0, 20/13139-0)
LOBBA, ALINE R. M.; ALVAREZ-FLORES, MIRYAM PAOLA; FESSEL, MELISSA REGINA; BURI, MARCUS VINICIUS; OLIVEIRA, DOUGLAS S. S.; GOMES, RENATA N. N.; CUNEGUNDES, PRISCILA S. S.; DEOCESANO-PEREIRA, CARLOS; CINEL, VICTOR D. D.; CHUDZINSKI-TAVASSI, ANA M. M.. A Kunitz-type inhibitor from tick salivary glands: A promising novel antitumor drug candidate. FRONTIERS IN MOLECULAR BIOSCIENCES, v. 9, p. 16-pg., . (20/13139-0, 18/20469-7, 13/07467-1, 18/10937-3, 15/50040-4)

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