Structural characterization of membrane protein complexes involved in bacterial cell wall biosynthesis

• Grant number: 13/22681-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: February 01, 2014
• End date: July 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Andrea Dessen de Souza e Silva
• Grantee: Lucas Mayrink Assis
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated research grant: 11/52067-6 - Assembly and structure of macromolecular complexes involved in bacterial cell wall: biosynthesis and virulence, AP.SPEC
• Associated scholarship(s): 15/20278-9 - Structural characterization of a membrane protein complex involved in bacterial cell wall synthesis, BE.EP.DD

Abstract

The cell wall plays an essential role in the maintenance of bacterial survival, preventing osmotic lysis and giving rigidity and shape to the cell. The enzymes involved in the biosynthesis of its central component, the peptidoglycan, have been used as targets for antibiotics for many years. However, the growing number of resistant strains brings about the need of studying and characterizing new molecular targets. In this sense, the objective of this work is to structurally characterize the complexes formed between flippases and PBPs, as well as flippases complexed with inhibitors. The solution of the atomic structures of these proteins will help in the development of novel inhibitors and will also allow for a better biochemical understanding of the cell wall biosynthetic process. The methodologies used to achieve these objectives will include the expression and purification of proteins, as well as experiments performed on the LNLS synchrotron in Campinas-SP. Additionally, the LNBio molecular library will be used in the search of the new inhibitors for the flippases. The thematic project entitled "Structuring of macromolecular complexes of bacterial wall" led by Andréa Dessen, comprises of a laboratory at the National Laboratory Of Biosciences (LNBio) in Campinas- SP, with four researchers, as well as a laboratory at the Institut de Biologie Structurale (IBS) in Grenoble, France, with ten researches. The group also has a collaboration with the laboratory of Dr. Eefjan Breukink in Utrecht, Holland. The student will perform most of the doctoral work at LNBio. However, due to the large experience of the Grenoble researchers with membrane protein crystallization techniques, it is expected that the student will acquire further experience performing some of the procedures of this project in Grenoble. The results obtained with this study will assist towards a greater understanding of the peptidoglycan synthesis process and how it relates with other steps of the bacterial life cycle. In addition, proteins structures solved in this project will allow for the exploration of flippases as new targets for antimicrobial development. (AU)

Scientific publications

(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)

ASSIS, L. MAYRINK; NEDELJKOVIC, M.; DESSEN, A.. New strategies for targeting and treatment of multi-drug resistant Staphylococcus aureus. DRUG RESISTANCE UPDATES, v. 31, p. 1-14, MAR 2017. (13/22681-0, 11/52067-6)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ASSIS, Lucas Mayrink. Structural and functional characterization of membrane proteins involved in the peptidoglycan synthesis. 2017. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.