BrainMap

Mrs. Alina-Diana Zamfir

Prof. Dr. Habil.

Professor - UNIVERSITATEA AUREL VLAICU ARAD

Other affiliations

Research associate (senior researcher, CS I) - INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU ELECTROCHIMIE SI MATERIE CONDENSATA - INCEMC TIMISOARA (Romania)

PhD Supervisor, Faculty/Doctoral School of Physics - UNIVERSITATEA DE VEST TIMISOARA (Romania)

Researcher | Teaching staff | Scientific reviewer | PhD supervisor

Alina D. Zamfir, PhD in Physics (2001), habilitation in Biophysics (2006, University of Münster, Germany), habilitation in Physics (2013, West University of Timisoara) is Professor at Aurel Vlaicu University of Arad and Head of Biological Mass Spectrometry Group – National Institute for R&D in Electrochemistry and Condensed Matter, Timisoara. Her research is focused on the development of novel mass spectrometry methods for biomedical research. Dr. Zamfir published 132 articles (WOS) in prominent journals such as Angewandte Chemie, Lab Chip, Analytical Chemistry, Analyst, Glycobiology, Journal Am. Soc. Mass Spectrom., Biophysica and Biochimica Acta etc., which collected so far over 2592 citations (WOS), Hirsch index 30 (WOS) and prestigious prizes. Dr. Zamfir conducted 17 research projects, gave over 300 presentations at international scientific meetings and published 15 book chapters with international publishing houses (Humana Press, Springer, Wiley, Elsevier, RSC, CRC Press etc).

Web of Science ResearcherID: https://www.webofscience.com/wos/author/record/B-6548-2011

Curriculum Vitae (12/05/2024)

Expertise & keywords

Interactomics of galactosaminoglycans in the extracellular matrix by advanced mass spectrometry Call name: Joint Applied Research Projects - PCCA 2013 - call
PN-II-PT-PCCA-2013-4-0191 2014 - 2017

Role in this project:

Coordinating institution: UNIVERSITATEA AUREL VLAICU ARAD

Project partners: UNIVERSITATEA AUREL VLAICU ARAD (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU ELECTROCHIMIE SI MATERIE CONDENSATA - INCEMC TIMISOARA (RO); CROMATEC PLUS SRL (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU ELECTROCHIMIE SI MATERIE CONDENSATA - INCEMC TIMISOARA (RO)

Project website: http://uav.ro/ro/cercetare/proiecte-in-desfasurare/pn-ii-pt-pcca-2013-4-0191

Abstract:

Proteoglycans are heavily glycosylated proteins, covalently linked to one or more glycosaminoglycan (GAG) chains, which are abundantly expressed in the extracellular matrix. At this level, proteoglycans play a key biological role, being implicated in a variety of physiological and pathological processes. There are strong evidences that chondroitin/dermatan sulfate (CS/DS) type of GAGs regulate angiogenesis and melanoma cell invasion and proliferation, most probably through their functional interactions. Among proteoglycans, biglycan is one of the most intriguing and highly versatile species being equipped with recognition markers both on the two encompassed CS/DS chains and on the protein moiety. Unlike the case of heparin and heparan sulfate type of GAGs, recognized as interacting with fibroblast growth factors (FGF), much less is known on the potentially active domains of CS/DS and almost nothing for the case of biglycan-derived chains. Moreover, the knowledge on the nature of FGF-2 binding domain within CS/DS, the core protein from which the interacting CS/DS derive and of the bound sequence in FGF-2 is at present solely at the level of speculation.

In view of this state-of-art, within ANCS/UEFISCDI PCCA 2013 call, priority field 4 Health, thematic area 4.1.3 Investigation and Intervention Methods Based on Molecular and Cellular Medicine, Genomics and Proteomics we proposed here a transdisciplinary project connecting molecular medicine, glycomics, glycoproteomics, advanced high resolution and microfluidics-based electrospray (ESI) mass spectrometry (MS), nanotechnology and bioinformatics for the determination of functional GAG interactomics. Within the project, biglycan released CS/DS chains will be depolymerized using specific lyases and subsequently purified. The resulting oligosaccharide mixture will be thoroughly characterized by advanced MS techniques in terms of epimerization, repeating dissacharide structure and sulfation pattern i.e. number of sulfate groups and their precise location along the chain and within the sugar ring. The CS/DS mixture will be subjected to noncovalent interactions with FGF-2. The interaction dynamics and the formed noncovalent complexes will be assessed by two high performance MS methods to be used complementarily: fully automated chip-based nanoESI high capacity ion trap (HCT) MS and a high resolution instrument, quadrupole time-of-flight (QTOF) MS. The structural analysis of the formed complexes will be achieved by top-down complex fragmentation by collision-induced dissociations (CID) and electron transfer dissociation (ETD). Data on the structure and sulfation pattern of the bound CS/DS motifs as well as of the protein sequence participating in the interaction will be collected. To enhance the ionization of the intact complexes a novel nanoESI ion source will be developed and applied within the project life-time to CS/DS, FGF-2 and CS/DS-FGF-2 complex analysis. The bioinformatics tools, including a novel computer software for automatic assignment of CS/DS and CS/DS-FGF-2 mass spectra and a database of all structures and active domains identified, will complete the analytical platform developed in the present project.

From the practical point of view the project contribution to the field progress resides in the introduction of original concepts and innovative approaches in GAG interactomics, which are adaptable also to other carbohydrate categories and relevant to various studies in molecular medicine. Further refinement of the methodologies conceived and optimized here, for routine applicability in early diagnosis of malignant transformations as well as for development of drugs able to inhibit detrimental carbohydrate-protein interactions, are clearly envisaged.

Functionalized polysaccharides for applications in biomedicine and biotechnology Call name: Joint Applied Research Projects - PCCA-2011 call, Type 1
PN-II-PT-PCCA-2011-3.1-0187 2012 - 2016

Role in this project:

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE " VICTOR BABEŞ " TIMISOARA

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE " VICTOR BABEŞ " TIMISOARA (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU ELECTROCHIMIE SI MATERIE CONDENSATA - INCEMC TIMISOARA (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU ELECTROCHIMIE SI MATERIE CONDENSATA - INCEMC TIMISOARA (RO)

Project website: http://www.umft.ro/pniiptpcca2011310187_308

Abstract:

Various natural polysaccharides are readily available for chemical modification or as building blocks for the synthesis of hybrid materials. However, because of the inherent difficulties in functionalization at preparative scale and subsequent analysis by reliable bioanalytical methods of long-chain polysaccharides, the research in the field is presently restricted to a few protocols of limited efficiency and inapplicable to complex mixtures of high heterogeneity in their polymerization degree and high molecular weight glycan chains. In this context, the objective of the BIOPOLIZAH project is to develop original and highly efficient strategies to allow for the first time functionalization at preparative scale of long chain, polydisperse mixtures of polysaccharides with functional groups such as aromatic amines, oligopeptides and chromophores, followed by detailed analysis of the coupling products using the most advanced glycoscreening and sequencing methods based on high performance mass spectrometry (MS), microfluidics technology and robotics for sample infusion into MS. The final goal is to create a platform for routine production of functionalized polysaccharides and their analysis by mass spectrometry. By developing highly sensitive, accurate microfluidic-based MS methods complemented by bioinformatics tools for data interpretation, sorting and validation the multi-disciplinary BIOPOLIZAH project will be able to screen and identify in a high-throughput regime long chain functionalized glycans. For this reason, the research within this project will lead to the development of novel concepts in carbohydrate synthesis/functionalization and their structural analysis which will open new directions in the fields of polymer synthesis, glycomics and glycoconjugates, biological mass spectrometry and bioinformatics.

Development of chip-based nanoelectrospray in combination with electron transfer dissociation mass spectrometry for top-down proteomics Call name: Exploratory Research Projects - PCE-2011 call
PN-II-ID-PCE-2011-3-0047 2011 - 2016

Role in this project:

Coordinating institution: Universitatea Aurel Vlaicu din Arad

Project partners: Universitatea Aurel Vlaicu din Arad (RO)

Affiliation: Universitatea Aurel Vlaicu din Arad (RO)

Project website: http://www.uav.ro/ro/cercetare/proiecte-in-desfasurare/project-pn-ii-id-0047-2011

Abstract:

The most popular method for protein de novo identification by mass spectrometry (MS)is based on enzymatic digestion rendering peptides to be analyzed by conventional tandem MS, in the so-called bottom-up approach. Though this method has brought a significant progress to the field, many limitations such as the low throughput and impossibility to characterize in details post-translational modifications, were reported. Therefore, a hot topic in MS-based proteomics is nowadays the development of novel top-down approaches based on intact protein fragmentation by electron transfer dissociation (ETD) technique.

In this context, here, an exploratory research project within the IDEAS-2011 call planning to combine for the first time chip-based-MS with ETD and implement it in proteomics and glycoproteomics is proposed. High expertise in MS and life sciences for method application to protein and glycoprotein analysis is a prerequisite for the project.

This superior analytical platform, integrating microfluidics technology with ETD-top-down fragmentation could allow efficient structural investigation of proteins in single, high throughput MS experiments. Such a technique may represent a viable alternative to current MS canons in proteomics, with real potential to influence directions of basic research in the field. The novel method and designed analysis protocols are aimed to find application in medicine as rapid and accurate diagnostic tools based on protein molecular fingerprints.

Glycomics of brain glycosaminoglycans by advanced mass spectrometric and related hyphenated techniques Call name: Projects for Young Research Teams - TE-2011 call
PN-II-RU-TE-2011-3-0008 2011 - 2014

Role in this project:

Coordinating institution: Universitatea Aurel Vlaicu din Arad

Project partners: Universitatea Aurel Vlaicu din Arad (RO)

Affiliation:

Project website: http://www.uav.ro/ro/cercetare/proiecte-in-desfasurare/project-pn-ii-ru-te-0008-2011

Abstract:

Chondroitin sulfate (CS) and dermatan sulfate (DS) glycosaminoglycans (GAG) are covalently linked to core proteins, forming proteoglycans (PG) with a wide distribution in extracellular matrix of brain. Recent studies have shown that proportion of CS/DS disaccharide units differing in the degree and profile of sulfation are involved in the functional diversity of neurons; however, so far not detailed structural analysis of brain GAGs was pursued. To close this gap, we want to introduce for the first time in glycomics of brain GAGs, an advanced mass spectrometry (MS)-based system based on fully automated chip nanoelectrospray ionization (nanoESI) and multistage MS (MSn) for structural investigation up to decasaccharides CS/DS chains regarding the sulfation pattern. The strategy requires the combination of biochemical tools and an analytical platform. CS/DS chains released by beta-elimination are purified and depolymerized with chondroitin AC lyase in parallel with chondroitin B lyase. The mixture of chains with different size length will be separated on size exclusion chromatography (SEC). The collected fractions from SEC are automatically infused into MS by chip-nanoESI. The species with the same length but different sulfation content are screened and isolated for MSn experiments. MSn technique is able to provide fine structural information about sulfate content and to determine for the first time the position of sulfate group inside the monomer ring for longer CS/DS chain.

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator
List of research grants as partner team leader
List of research grants as project coordinator or partner team leader
Significant R&D projects for enterprises, as project manager
R&D activities in enterprises
Peer-review activity for international programs/projects