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Program for prof. Michael Butler visit: training on glycosylation on recombinant protein

Grant number: 13/00946-1
Support type:Research Grants - Visiting Researcher Grant - International
Duration: April 24, 2013 - May 15, 2013
Field of knowledge:Interdisciplinary Subjects
Principal Investigator:Carlos Augusto Pereira
Grantee:Carlos Augusto Pereira
Visiting researcher: Michael Butler
Visiting researcher institution: University of Manitoba, Canada
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The aim of Prof. Michael Butler visit is to train researchers from Instituto Butantan (LIV) and Unifesp (ICT, Campus São José dos Campos) on Post-translational modifications (MPT) of recombinant proteins, focusing more specifically on Glycosylation, which has enormous implications over the quality of these molecules. Since, part of the program includes a gradute course, this training program will be accessible to researchers and students from other Institutions in São Paulo. Frequently, the so-called glycoproteins have a complex three-dimensional molecular structure, characterized by a sequence of amino acids and chemical bonds between them, as well as additional MPT which are decisive for the final conformation of the protein and its biological activity(1-3). These MPT occur inside the cells after the synthesis of the polypeptide chain and may involve, among others, the formation of disulfide bonds, ³-carboxylations, hydroxylations and O-and N-glycosylations, the last being the most frequent in this type of molecule, then the most studied (3). Glycosylation is an enzymatic process occurring at the endoplasmic reticulum and Golgi complex, that links, in a sequential manner, glycans to newly synthesized polypeptide chains. This structure represents up to 45% of the molecular weight (3) and is responsible for the main biological characteristics (1). The existence of incomplete enzymatic reactions results in glycoform profiles which depend directly on culture conditions (2-4). Cell lineages used, always eukaryotic, are also determinants. So, in this type of expression system, more than in any other, the process determines the final product and its quality (2, 4).MPT are extremely relevant for present and future projects developed at IBu-LVI and Unifesp-ICT (e.g. attached file), but attempting to enable the groups on these subjects, we identify a clear gap in Brazil, mainly in applied and technological skills. Therefore, to fulfill this deficiency, we conceived this program as a graduate course (open also to non-academic participants) and a series of meetings with Prof. Butler to more specific discussions on our projects needs. It includes also visitation to Laboratories at São Paulo that maintain relationship with our groups (EPUSP, FEQ-Unicamp, DEQ-USCar, IPEN, IPT) or with Prof. Butler (IQ-USP).Prof. Butler is a respected researcher and editor of several magazines who published more than 120 papers and book chapters, and 7 books, several of them in the specific theme of this training program. It is also a longtime contributor to IPT and IBu, proponents of this program, as well as to other researchers and institutions in Latin America: he edited a book with proponents (see ref. 3 below); Elisabeth Augusto and Ana Moro (IBu) are part of organizing committee at the 8th PEACE Conference (Protein expression in animal cells), event chaired by Prof. Butler (Angra dos Reis, RJ, 2007); he gave a short course on "Animal cell cultivation" (13th Sinaferm; UFSCar, São Carlos, 1996); he received many Brazilian researchers in his lab for specific training (e.g.: Tatiane Coelho-IQUSP, 2011; Elisabeth Augusto in 1994); among others. 1. WALSH G, JEFFERIES R. Nat Biotechnol. v. 24, p.241-1252, 2006.2. SCHELLKENS H. Nephrology Dialysis Transplantation Plus, v.2, p.i27-i36, 20093. BUTLER M. Post-translational modification of recombinant proteins. In: Castilho LR, Moraes AM, Augusto EFP, Butler M (eds). Animal cell technology. Roca Editora: São Paulo, 2008, 518p.4. KANNICHT C (ed). Post Translational Modifications of Proteins. Humana Press, 2008, 390p. 5. CHA HJ et al. Biochem Eng J, v. 24, p. 225-233, 2005. (AU)