Novel mass spectrometry-based technologies for post-translational modifications analysis

• Grant number: 21/14751-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2022
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Giuseppe Palmisano
• Grantee: Simon Ngao Mule
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications, AP.JP2
• Associated scholarship(s): 24/03954-0 - Modulation of protein glycosylation during metacyclogenesis of Trypanosoma cruzi strains with varying degrees of pathogenicity, BE.EP.PD

Abstract

Protein O-linked glycosylation is a post-translational modification (PTM) of proteins at serine or threonine hydroxyl functional groups. This PTM plays important roles including mammalian cell adhesion, functional determinants for antibody recognition, regulation of protein stability and activity, targeting of glycoproteins, and in host-parasite interaction where, for example, Trypanosoma cruzi, the etiological agent of Chagas disease (American Trypanosomiasis) interacts with host cells during recognition, adhesion and infection. This disease is a neglected tropical disease endemic in latin American countries, and that leads to cardiomyopathy, megaviscera or neurological complications in the chronic phase of the disease. A better understanding of T. cruzi-host interaction will help prioritize new therapeutic targets. Despite the key roles of protein O-linked glycosylation, method development strategies for this PTM has lagged behind. In the proposed study, the development of an analytical method for the study of O-linked glycoprotein will be sought. The development of new analytical methods for analyzing PTMs will offer the possibility to detect protein modifications in complex biological systems with high precision and sensitivity, expanding our current knowledge. In particular, the identification of protein glycosylation at different life stages of T. cruzi belonging to different genetic subdivisions (TcII and TcVI) and host cells will be evaluated and associated with the expression of specific glycosyltransferases. Large scale cell surface glycoproteome and glycome analysis combined with functional assays will be used as a molecular determinant linking glycosylation enzyme expression and phenotype. Inhibitors of protein glycosylation will be evaluated as potential chemotherapeutic target of T. cruzi.

Scientific publications

(4)

(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)

MULE, SIMON NGAO; SAAD, JOYCE SILVA; SAUTER, ISMAEL PRETTO; FERNANDES, LIVIA ROSA; DE OLIVEIRA, GILBERTO SANTOS; QUINA, DANIEL; TANO, FABIA TOMIE; BRANDT-ALMEIDA, DEBORAH; PADRON, GABRIEL; STOLF, BEATRIZ SIMONSEN; et al. The protein map of the protozoan parasite Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum during growth phase transition and temperature stress. JOURNAL OF PROTEOMICS, v. 295, p. 17-pg., 2024-01-29. (21/14751-4, 16/23689-2, 20/04923-0, 18/18257-1, 18/15549-1, 17/04032-5, 20/13562-0, 21/08915-4, 18/13283-4)

BARBOZA, BRUNO RAFAEL; MACEDO-DA-SILVA, JANAINA; SILVA, LAYS ADRIANNE MENDONCA TRAJANO; DE MORAIS GOMES, VINICIUS; SANTOS, DEIVID MARTINS; MARQUES-NETO, ANTONIO MOREIRA; MULE, SIMON NGAO; ANGELI, CLAUDIA BLANES; BORSOI, JULIANA; MORAES, CAROLINA BORSOI; et al. ST8Sia2 polysialyltransferase protects against infection by Trypanosoma cruzi. PLoS Neglected Tropical Diseases, v. 18, n. 9, p. 33-pg., 2024-09-01. (22/00796-9, 21/14751-4, 20/04923-0, 18/18257-1, 21/00140-3, 18/15549-1, 20/02988-7, 22/09915-0, 21/00507-4, 23/02096-7, 21/14179-9)

MULE, SIMON NGAO; ALEMAN, EVARISTO VILLALBA; ROSA-FERNANDES, LIVIA; SAAD, JOYCE S.; DE OLIVEIRA, GILBERTO SANTOS; MARTINS, DEIVID; ANGELI, CLAUDIA BLANES; BRANDT-ALMEIDA, DEBORAH; CORTEZ, MAURO; LARSEN, MARTIN ROSSEL; et al. Leishmaniinae: Evolutionary inferences based on protein expression profiles (PhyloQuant) congruent with phylogenetic relationships among Leishmania, Endotrypanum, Porcisia, Zelonia, Crithidia, and Leptomonas. PROTEOMICS, v. 24, n. 18, p. 17-pg., 2024-06-08. (21/14751-4, 16/23689-2, 20/04923-0, 18/18257-1, 18/15549-1, 17/04032-5, 20/13562-0, 21/14179-9, 18/13283-4)

SANTIAGO, VERONICA FEIJOLI; DOMBROWSKI, JAMILLE GREGORIO; KAWAHARA, REBECA; ROSA-FERNANDES, LIVIA; MULE, SIMON NGAO; MURILLO, OSCAR; SANTANA, THAIS VIGGIANI; PACCINI COUTINHO, JOAO VICTOR; MACEDO-DA-SILVA, JANAINA; LAZARI, LUCAS CARDOSO; et al. Complement System Activation Is a Plasma Biomarker Signature during Malaria in Pregnancy. GENES, v. 14, n. 8, p. 20-pg., 2023-08-01. (21/14751-4, 18/15549-1, 20/06747-4, 20/04923-0, 17/04032-5, 21/00140-3, 19/12068-5, 18/20468-0)