BrainMap

Elena Matei

Researcher - INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU TEHNOLOGII IZOTOPICE SI MOLECULARE I N C D T I M

Researcher

Web of Science ResearcherID: AAP-8706-2020

Curriculum Vitae (20/02/2024)

Expertise & keywords

Molecular aggregation pathway, and in silico inhibitors screening of cataract-associated gamma D-crystallin congenital defect Call name: P 4 - Proiecte de cercetare exploratorie - PCE-2021
PN-III-P4-PCE-2021-0316 2022 - 2024

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU TEHNOLOGII IZOTOPICE SI MOLECULARE I N C D T I M

Project partners: INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU TEHNOLOGII IZOTOPICE SI MOLECULARE I N C D T I M (RO)

Affiliation:

Project website: https://www.itim-cj.ro/PNCDI/antictract/

Abstract:

Cataract is a major cause of blindness worldwide, either as a result of age-related degenerative modifications, or genetic mutations, causing abnormal aggregation of eye lens crystallins. While age-related cataracts occur only in adults, inherited congenital cataracts manifest in early childhood. Currently the only effective treatment that can be applied for cataract is surgery, without any possibility of prevention. A complete elucidation of the molecular mechanism of crystallin aggregation is essential for understanding cataract formation. The proposed research aim to investigate the molecular aggregation pathway of the Pro23Thr mutation in human gamma D-crystallin (hγD-P23T), as a representative variant causing congenital cataract. We plan to get new insights into the interaction mechanism inside the eye lens causing hγD-P23T aggregation, and its escape from chaperone surveillance. In addition, potential inhibitors interfering with the phase-separation mechanism, will be tested against hγD-P23T aggregation.

This work will involve methods that allow structural, and interactions details inside eye lens, primarily NMR spectroscopy, ITC, in silico inhibitors screening, aggregation supperssion bioassay in vitro, and molecular docking. Combining this integrated structural biology approach to study cataract, is a promising perspective for the anti-cataract drug development.

Structures, carbohydrate binding and anti-viral activity of CVNH and OAAH family (R01 grant funded by National Institute of Health , USA ) Call name:
2012 - 2016

Role in this project: Key expert

Coordinating institution: University of Pittsburgh

Project partners: University of Pittsburgh ()

Affiliation: University of Pittsburgh ()

Project website:

Abstract:

Lectins are well known, multifaceted carbohydrate binding proteins that specifically recognize diverse sugar structures and mediate a variety of biological processes such as cell-cell and host-pathogen interactions, serum glycoprotein turnover and innate immune responses. In 1998, our laboratory solved the first solution structure of a cyanobacterial-derived protein, cyanovirin (CV-N) that exhibited potent HIV- inactivating properties. The structure revealed a novel three-dimensional fold, distinct from any known lectin folds. Extensive biochemical and structural characterizations based on our initial results and primarily from our laboratory led to the categorization of the new structural CVNH family. We previously determined a substantial number of type I CVNH proteins and are now embarking on structure/function studies of type III CVNHs. Similar to our work with CVN, we now have determined the three-dimensional structure of Oscillatoria Agardhii Agglutinin (OAA), another cyanobacterial anti-HIV lectin that shares sequence similarity with eight other proteins, the new OAAH family. No structural, carbohydrate-binding or other functional data were available prior to our recent first structure and no data on any of the family members is available. The long-term goal of this proposal is to understand the molecular mechanisms and structural basis of oligosaccharide recognition and the mode of action of HIV-inactivating lectins.

We aim to gain a comprehensive molecular understanding of several classes of antiviral lectins and continue with our vigorous program that focuses on elucidating the structural, biochemical, and thermodynamic properties of type III CVNH family members as well as members of the new OAAH family. Results from this work will provide avenues to exploit these lectins in the fight against AIDS.

Photogenerated Carbohydrate Microarrays (2R01 grant funded by National Institute of Health , USA ) Call name:
2011 - 2013

Role in this project: Partner team leader

Coordinating institution: University of Massachusetts , USA

Project partners: University of Massachusetts , USA ()

Affiliation: University of Massachusetts , USA ()

Project website:

Abstract:

Carbohydrate recognition plays a central role in many biological and disease processes. Protein-carbohydrate recognition is also of emerging medical importance, for example in combating infection, controlling the spread of tumors, and the development of targeting drugs. Carbohydrate microarrays have been identified as one of the most important tools for rapid probing of functional properties of complex glycosylation patterns of proteins and cells. At present, carbohydrate microarrays are still in the early development phase, in part hampered by complex preparation protocols. New, simple and robust methods to array fabrication are needed, both on the carbohydrate chemistry level, as well as the surface chemistry level. The present application focuses on the design and development of a fundamentally new microarray chemistry that is fast and is easily modulated by external light. The photoligation technique used in the array fabrication is versatile, can accommodate a variety of carbohydrate structures, and is highly compatible with existing microarray technologies. In this work, special emphasis will be placed on the control of ligand display with respect to binding affinity and specificity. In addition, solution binding studies will be undertaken to further test the array chemistry and reliability of the created arrays in order to generate trustworthy screening results.

Carbohdyrate binding and anti-viral activity of cyanovirin-like lectins (R01 grant funded by National Institute of Health, USA ) Call name:
2007 - 2012

Role in this project: Key expert

Coordinating institution: University of Pittsburgh

Project partners: University of Pittsburgh ()

Affiliation: University of Pittsburgh ()

Project website:

Abstract:

Cyanovirin (CVN) like lectins represent a new class of anti-viral agents. The long-term goal of this proposal is to understand the molecular mechanisms and structural basis of high-affinity oligosaccharide recognition and the mode of anti-viral activity of these proteins. Lectins are well known, multifaceted carbohydrate binding proteins that specifically recognize diverse sugar structures and mediate a variety of biological processes such as cell-cell and host-pathogen interactions, serum glycoprotein turnover and innate immune responses. Although a number of lectins have been well studied, ambiguities still exist about their precise biological roles. In 1998, our laboratory solved the first structure of a cyanobacterial derived protein, cyanovirin, that exhibited potent HIV-inactivating properties. The structure revealed a novel threedimensional fold, distinct from any known lectin folds. Extensive biochemical and structural characterizations based on our initial results and primarily from our laboratory revealed that CVN's mode of action involves recognition of N-linked high-mannose oligosaccharides (Man-8 and Man-9) on gp120, resulting in viral inactivation. The structure of CVN resulted in the definition of a new structural class of lectins (CVNH family), with CVN as the class defining member. However, except for CVN, no atomic structures of any other CVNH family member have been reported and the precise structure/function relationships of all CVNH proteins remains poorly understood. We will determine structures of several representative members of this family to identify the relationship between sequence and structure conservation and establish the structural basis for high-affinity and specificity of carbohydrate recognition for this class of lectins. This will allow us to further exploit the potent anti-viral properties of this protein family, aiding in devising novel strategies for controlling the spread of AIDS, a major global health treat. Overall, we wish to establish the structural and thermodynamic basis for the cyanovirin-like lectincarbohydrate interactions as a paradigm for multivalent and multi-site binding and how these binding events relate to the unique anti-viral properties of this lectin class. Using a battery of state-of-the-art structural/functional/chemical approaches, we will undertake a vigorous investigation on a number of cyanovrin-like lectins. We believe our multidisciplinary study will not only lead to a fundamental understanding of protein-carbohydrate recognition involved in critical cellular functions, but also contribute to the development of drugs for potential therapeutic use as anti-viral agents.

FILE DESCRIPTION	DOCUMENT
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