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A network for an integrative biology in neglected diseases: bridging epigenetics, metabolism and cell cycle in pathogenic trypanosomatids


Pathogenic trypanosomatids such as Leishmania spp. and Trypanosoma cruzi are the causative agents of leishmaniosis and Chagas disease, a group of neglected diseases endemic in the tropical and subtropical belt of the planet and the Americas, respectively. The therapeutic approaches against these diseases are largely unsatisfactory due to toxicity and emergence of resistance. Thus, new drugs are urgently needed against these threats. In the last 20 years, a profusion of OMICS approaches resulted in a deeper comprehension of cellular processes allowing the survival of these parasites in their hosts, a sine qua non condition for establishing the infection and triggering the pathology. However, most of these studies approached cellular processes individually; as a consequence our comprehension of their integration is poor. The goal of this proposal is to understand the interaction among three essential core processes: metabolism, cell cycle and epigenetic gene expression regulation, with the goal of establishing a broader comprehension of how the metabolic environment affects parasite proliferation and determines inheritable adaptations. The information to be obtained will be fundamental to elucidate the basic biology of these pathogens as well as to discover new druggable points, greatly contributing for the development of novel therapies. (AU)

Articles published in other media outlets (3 total):
Nexo Jornal: Uma agenda para as doenças esquecidas (12/Apr/2021)
IFSC/USP - Instituto de Física de São Carlos da Universidade de São Paulo: Coronavirus X doenças tropicais negligenciadas (13/Apr/2021)
Jornal da Ciência online: Uma agenda para as doenças esquecidas (07/Apr/2021)

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)
SOUZA, RODOLPHO ORNITZ OLIVEIRA; DAMASCENO, FLAVIA SILVA; MARSICCOBETRE, SABRINA; BIRAN, MARC; MURATA, GILSON; CURI, RUI; BRINGAUD, FREDERIC; SILBER, ARIEL MARIANO. Fatty acid oxidation participates in resistance to nutrient-depleted environments in the insect stages of Trypanosoma cruzi. PLOS PATHOGENS, v. 17, n. 4 APR 2021. Web of Science Citations: 0.
VILLAFRAZ, ORIANA; BIRAN, MARC; PINEDA, ERIKA; PLAZOLLES, NICOLAS; CAHOREAU, EDERN; ORNITZ OLIVEIRA SOUZA, RODOLPHO; THONNUS, MAGALI; ALLMANN, STEFAN; TETAUD, EMMANUEL; RIVIERE, LOIC; SILBER, ARIEL M.; BARRETT, MICHAEL P.; ZIKOVA, ALENA; BOSHART, MICHAEL; PORTAIS, JEAN-CHARLES; BRINGAUD, FREDERIC. Procyclic trypanosomes recycle glucose catabolites and TCA cycle intermediates to stimulate growth in the presence of physiological amounts of proline. PLOS PATHOGENS, v. 17, n. 3 MAR 2021. Web of Science Citations: 1.
LIMA, ALEX R. J.; DE ARAUJO, CHRISTIANE B.; BISPO, SALOE; PATANE, JOSE; SILBER, ARIEL M.; ELIAS, M. CAROLINA; DA CUNHA, JULIA P. C. Nucleosome landscape reflects phenotypic differences in Trypanosoma cruzi life forms. PLOS PATHOGENS, v. 17, n. 1 JAN 2021. Web of Science Citations: 0.
SHIRATSUBAKI, ISABEL S.; FANG, XIN; SOUZA, RODOLPHO O. O.; PALSSON, BERNHARD O.; SILBER, ARIEL M.; SIQUEIRA-NETO, JAIR L. Genome-scale metabolic models highlight stage-specific differences in essential metabolic pathways in Trypanosoma cruzi. PLoS Neglected Tropical Diseases, v. 14, n. 10 OCT 2020. Web of Science Citations: 0.
DE LIMA, LOYZE P.; POUBEL, SALOE BISPO; YUAN, ZUO-FEI; ROSON, JULIANA NUNES; DE LUNA VITORINO, FRANCISCA NATHALIA; HOLETZ, FABIOLA BARBIERI; GARCIA, BENJAMIN A.; CHAGAS DA CUNHA, JULIA PINHEIRO. Improvements on the quantitative analysis of Trypanosoma cruzi histone post translational modifications: Study of changes in epigenetic marks through the parasite's metacyclogenesis and life cycle. JOURNAL OF PROTEOMICS, v. 225, APR 15 2020. Web of Science Citations: 0.
PAVANI, RAPHAEL S.; DE LIMA, LOYZE P.; LIMA, ANDRE A.; FERNANDES, CARLOS A. H.; FRAGOSO, STENIO P.; CALDERANO, SIMONE G.; ELIAS, MARIA CAROLINA. Nuclear export of replication protein A in the nonreplicative infective forms of Trypanosoma cruzi. FEBS Letters, v. 594, n. 10 MAR 2020. Web of Science Citations: 0.

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