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Júlia Costa Lab

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We are studying structures and functions of glycosylation, which is an important post-translational modification of proteins in human cells, with implications in biomarker discovery.

Júlia Costa
Principal Investigator
PhD in Biochemistry (1994), University of Lisbon

Phone (+351) 214469437 | Extension 1466
jcosta@itqb.unl.pt

ORCiD

 

Research Interests

Most mammalian proteins contain covalently linked oligosaccharides. Secretory and membrane proteins are N- and O-glycosylated concomitantly to their transport along the secretory pathway, and a large diversity of glycosidases and glycosyltransferases characteristic of the host cells are involved in these post-translational modifications. Oligosaccharides have been shown to be important for several events including protein folding and stability, intracellular transport, cell-cell interactions and signalling.

In the Laboratory of Glycobiology, we are studying structural and functional aspects of protein glycosylation with impact in health. At present two major lines of work are being developed. The first aims at biomarker identification from the blood and cerebrospinal fluid of patients with the neurodegenerative disease amyotrophic lateral sclerosis (ALS) using systematic approaches (glycomics, proteomics) and targeted approaches (ELISA). ALS has an incidence of 2–3/100,000 in Europe and life expectancy is within 2–5 years after first symptoms. The identification of a biomarker for ALS would be useful in diagnosis, prognosis, to monitor the effect of therapeutic interventions and to understand disease etiopathogenesis.

Another area of development in the lab consists of studying protein glycosylation from extracellular vesicles (EVs). EVs are released by virtually all cells, carry cellular molecules to the extracellular environment being considered as surrogates of the originating cells, and they are capable of crossing biological barriers. More recently, EVs have been found to display characteristic glycosignatures, which can be explored in context of their potential as targets for biomarker discovery and as carriers in drug delivery.

Techniques used for protein glycosylation analysis include lectin blotting, liquid chromatography and mass spectrometry. Modulation of glycosylation has been accomplished in vitro with glycosidases and recombinant glycosyltransferases, and in vivo by silencing or overexpression of relevant glycosyltransferases.

Selected Publications

  1. Sandau US, Magaña SM, Costa J, Nolan JP, Ikezu T, Vella LJ, Jackson HK, Moreira LR, Palacio PL, Hill AF, Quinn JF, Van Keuren-Jensen KR, McFarland TJ, Palade J, Sribnick EA, Su H, Vekrellis K, Coyle B, Yang Y, Falcón-Perez JM, Nieuwland R, Saugstad JA; International Society for Extracellular Vesicles Cerebrospinal Fluid Task Force (2024) Recommendations for Reproducibility of Cerebrospinal Fluid Extracellular Vesicle Studies. J. Extracel. Ves. 13:12397. doi: 10.1002/jev2.12397. 

  2. Vicente J, Guerreiro AC, Felgueiras B, Chapla DG, Moremen K, Costa J (2023) Glycosyltransferase 8 domain-containing protein 1 (GLT8D1) is a UDP-dependent galactosyltransferase. Sci. Rep. 13:21684. doi: 10.1038/s41598-023-48605-480.

  3. Costa J, Hayes C, Lisacek F (2023) Protein glycosylation and glycoinformatics for novel biomarker discovery in neurodegenerative diseases. Ageing Res Rev. 89, 101991. doi: 10.1016/j.arr.2023.101991.

  4. Costa J, Pronto-Laborinho A, Pinto S, Gromicho M, Bonucci S, Tranfield E, Correia C, Alexandre BM, de Carvalho M (2020) Investigating LGALS3BP/90K glycoprotein in the cerebrospinal fluid of patients with neurological diseases. Sci. Rep. 10, 5649. doi: 10.1038/s41598-020-62592-w.

  5. Costa J, Gatermann M, Nimtz M, Kandzia S, Glatzel M, Conradt HS. (2018) N-Glycosylation of Extracellular Vesicles from HEK-293 and Glioma Cell Lines. Anal Chem. 90, 7871-7879. doi: 10.1021/acs.analchem.7b054.

Glicobiologia (PT)

A glicosilação de proteínas é uma modificação pós-traducional muito abundante em mamíferos. Os oligossacáridos ligados covalentemente às proteínas desempenham funções importantes no seu folding e estabilidade, transporte intracelular, interacções célula-célula e sinalização. No Laboratório de Glicobiologia estudamos aspectos estruturais e funcionais de glicosilação de proteínas com impacto na saúde.

Correntemente, estão a ser desenvolvidas duas linhas de investigação principais. A primeira tem como objectivo a identificação de biomarcadores para a doença neurodegenerativa esclerose lateral amiotrófica que afecta os neurónios motores, usando técnicas de glicómica, proteómica e ELISA. A segunda consiste no estudo da glicosilação de vesículas extracelulares. De uma forma geral, as células libertam vesículas para o meio extracelular as quais são capazes de atravessar barreiras biológicas. Estas vesículas apresentam glicosilação característica o que poderá ter implicações na sua utilização para a identificação de novos biomarcadores bem como para o "delivery" de agentes terapêuticos.

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