BrainMap

Loredana Mereuta

Prof. PhD habil.

Professor - UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Researcher | Teaching staff | PhD supervisor

Expertise & keywords

New peptides for targeted cancer therapy and early diagnosis Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente - TE-2021
PN-III-P1-1.1-TE-2021-0331 2022 - 2024

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation:

Project website: https://www.uaic.ro/therhome/

Abstract:

In spite of the remarkable progress in the past years, cancer still represents a major challenge for scientific community. Especially, cancer cell detection in early stages of development is still problematic. Discovery of new peptides with high penetration capability of plasma membrane and specificity for receptors overexpressed in tumors is of particular interest for both, detection and development of new drug delivery systems. Tumor-homing peptides have a few properties over other systems that make them the best candidates for specific targeting: small size, low cost of production, flexibility in conjugation possibilities. Unfortunately, for most targeted therapies, the macromolecular drugs are taken into the cell through endocytosis and then end-up trapped into endosomes.

The goal of this project is to combine the specificity of homing peptides with special properties of membrane permeability of cell penetrating peptides and antimicrobial peptides, respectively, to generate new molecular tools with high degree of specificity and cell membrane permeability. Methods like fluorescence and super-resolution microscopy, electrophysiology, spectroscopy, cellular and molecular biology techniques will shed light into understanding the uptake mechanism, membrane trafficking and interactions with proteins of mechanosensitive pathways of cell migration of the new peptides.

Xeno nucleic acids-mediated, real-time multiplexed detection of disease relevant miRNAs, with single molecule sensitivity and selectivity Call name: P 4 - Proiecte de Cercetare Exploratorie, 2020
PN-III-P4-ID-PCE-2020-0011 2021 - 2023

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation:

Project website: https://www.uaic.ro/rna-nanodetect/

Abstract:

miRNAs are small non-coding RNAs which regulate gene expression at post-translational level, and the content of circulating miRNAs in biological fluids changes significantly during the onset and progress of major diseases. Therefore, miRNAs became important biomarkers, that could be used for disease diagnosis and prognosis. Herein we address fundamental problems in miRNA detection, by proposing a paradigm to allow their multiplexed, real-time monitoring, offering highly accurate electronic readout of miRNA profiles, without the need of labeling or amplification, thus rendering the approach straightforward and efficient. Our innovative strategy is set on three pillars: (i) we will use a nanopore platform as a single-molecule transducer of miRNA detection, enabling real-time, sensitive and selective miRNA detection from similar sequences; (ii) to achieve enhanced selectivity detection for miRNAs, we will employ as sensing elements a particular class of xeno nucleic acids, peptide-nucleic acids (PNA), functionalized with various length polycationic tags; (iii) the tactics of the proposed approach will result in the sensitive, multiplexed detection of different miRNA species during the same experiment. With PNA-conjugated hybrid nanopores working as arrays and miniature amplifiers built on custom ASICs, we envision that the results stemming from this proposal will pave the way toward cheap, fast and accurate, simultaneous detection of multiple miRNAs in point-of-care units.

Nanopore-based, ultra-sensitive and multivalent detection of short nucleic acid fragments, with functionalized gold nanoparticles Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2019-0037 2020 - 2022

Role in this project: Project coordinator

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: https://www.uaic.ro/nanosensedna/

Abstract:

Fast, cheap and accurate detection of endogenous or exogenous short DNA fragments, may enable early detection of various diseases or probe the presence of viral or microbial pathogens. In this proposal we aim at integrating two synergic nanotechnology tools, namely nucleic acids-functionalized gold nanoparticles (AuNPs) and nanopores, to provide a highly selective and sensitive ssDNA detection system in aqueous samples, also suitable for real-time recognition of single-nucleotide variations. To this end, the strategy involves: (i) protein nanopores-based analytes biosensing, and (ii) the use of peptide-nucleic acids (PNA) probes to serve at highly specific targets for ssDNA capture and recognition, via specific hybridization. The combined use of a PNA-nanopore system, as a single-molecule transducer of ssDNA detection, will provide exquisite specificity and sensitivity for real-time, label-free ssDNA detection. The specificity attribute arises as PNAs present greater binding affinity and selectivity versus conventional nucleic acid probes. The unsurpassed sensitivity of detection is imparted by: (i) the use of AuNPs functionalized with free- and thiol-terminated single stranded PNAs, targeted for multi-valent detection of specific ssDNAs, thus contributing to the lower ssDNA detection limit, and (ii) the capability of the presented platform for single particle detection and discrimination. The social benefits of this project lie, among others, on the future development of personalized care, provided based on the unique nucleic acid-entailed disease profile, and the facile implementation of real-time, cell-free circulating DNAs, liquid-biopsy-based assays. Integrating nanomanufacturing technologies combined with machine learning-based convolutional neural networks, to automatically extract single-molecule information from the ssDNA detection platform revealed herein, may provide a boosting to the multiplexed detection of multiple ssDNA biomarkers in a single run.

Label-free, real-time detection platform of Hepatitis B Virus antigens with protein biosensors Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-0016 2020 - 2022

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO); INSTITUTUL DE BIOCHIMIE (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: https://www.uaic.ro/hepatvirdetect/

Abstract:

Chronic Hepatitis B virus (HBV) is the cause for severe liver pathologies leading to ~ 1 million deaths per year, and Romania has among the highest incidence among EU countries. Screening and early clinic diagnosis are extremely relevant to prevent further viral spreading. Importantly, early productive infection can be evidenced by measuring the titers of the secretory HBV proteins, the “surface” (HBs) or “early” (HBe) antigens (Ag). The HBsAg is the first serological antigen detectable in serum ~ one week after HBV infection, followed by HBeAg, which becomes evident during viral replication. This proposal aims to place innovation at the heart of discovery, and develop a portable, label-free, first-generation protein-based nanosensor, for the sensitive and selective detection of HBeAg, by exploiting its interaction with the specific anti-HBe antibody. At the core of the endeavor lies an innovative sensing paradigm, according to which analytes of interest are identified as they disrupt the ionic current passing through a single nanopore. Knowing that nanopore technology evolved into a mature, single-molecule screening technology and revolutionized single-molecule detection, as done in Europe by Oxford Nanopore Technologies (https://nanoporetech.com), our platform will pave the way to developing nearly ideal sensors for HVB detection, for integration in low-cost, low-powered, portable, and wearable devices. Our project will start at technological readiness level, as we have preliminary data demonstrating the feasibility of the protein nanopore-based technology for the uni-molecular detection of analytes. Subsequently, we aim to harness our findings and bring them to the next level (TRL3), in which we will demonstrate and validate the ‘proof-of-concept’ of an integrated, portable device enabling the detection of HBeAg in a variety of real-world biological samples.

Emerging molecular technologies based on micro and nano-structured systems with biomedical applications Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0010 2018 - 2021

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); UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO); UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO); UNIVERSITATEA BABES BOLYAI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.itim-cj.ro/PNCDI/tehnobiomed/

Abstract:

The TehnoBioMed project aims to increase the institutional performance of 6 partners with a rich tradition in research, development and innovation (RDI) joined in a consortium with a strong interdisciplinary character designed to develop emerging molecular technologies based on micro- and nanostructured systems and dedicated to biomedical applications.

The project consortium consists of 6 partners distributed in 3 university centers with a tradition in the RDI activity: Cluj-Napoca, Bucharest, Iasi, and consists of 3 national institutes and 3 prestigious universities. The consortium partners are distributed in three different development regions of Romania.

The specific objectives of the project can be synthesized by: i) Manufacturing and testing of surfaces with antimicrobial properties obtained by micro- and nano-fabrication techniques and functionalized with antimicrobial peptides; ii) Development of molecular targeting drug systems by encapsulation in supramolecular structures of the dendrimeric type; iii) Carrying out, calibrating and testing a complex diagnostic equipment based on the principles of coherent optics and dedicated to obtaining high-resolution images in medicine and material science; iv) Development of new technologies for the detection and analysis of molecular biomarkers; v) Development of the technological potential of phycobiliproteins for the production of photosensitive materials with applications in new solar cells and new immunological sensors.

The project aims to develop new or significantly improved products / technologies / services of which we mention the following: Developing a high-resolution OCT imaging equipment with applications in biomedicine and material science; Designing, manufacturing and testing of a nano-ELISA technology; Making new systems with improved antimicrobial activity and increased efficiency against bacterial biofilm formation; Obtaining compounds/materials with impact in the prevention and control of infections.

Nanopore-based, pattern recognition on the primary structure of polypeptides at uni-molecular level Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2016-0508 2018 - 2020

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: https://science.research.uaic.ro/PepRec/

Abstract:

The primary structure of a peptide or protein is a key factor in determining how the overall structure folds and functions, making the peptide and protein sequencing one of the important tasks in proteomics. Conventional methods such as mass spectrometry and Edman degradation may fall short of probing subtle changes to the internal structure of chains, and they are costly- and labor-intensive. In this proposal, we aim at developing the proof-of-concept of sequence-based characterizations of peptides with α-hemolysin (α-HL) nanopores, at the single-molecule level. The paradigm of peptide sequencing with nanopores posits that a peptide guided across a nanopore, will uniquely modulate the ionic current flow through it, due to the distinct occlusions of the nanopore by aminoacids from the peptide’s sequence. The analysis of such current blockade events as they unfold in time, may yield insights into the peptide sequence. One of Achille’s heels of this approach is the relatively high velocity of the peptide, which precludes accurate reading of the blockade events with optimal signal-to-noise ratio. To alleviate this, we will probe herein a state-of-the-art approach to control the peptide’s translocation speed across a nanopore, by employing short peptides (~ 40 residues) whose N- and C-termini will be engineered to contain oppositely charged aminoacids. In the vicinity of the nanopore clamped at a given potential, the peptide it will be first guided inside it under the influence of electric field lines. Subsequently, the electric forces acting oppositely at the N- and C-termini, will increase both the polypeptide capture rate and mean residence time in the nanopore. The current fluctuations ensuing from the slowed-down movement of the peptide through the nanopore will be used to derive two-dimensional maps of relative current blockade and time of block, enabling us to implement computer-designed procedures to deliver the readout of the primary structure of the peptide.

A nanopore tweezer-based approach for studying intermolecular interactions at uni-molecular level. Application to exploring metal-mediated, mismatched base pairs hybridization in nucleic acids Call name: P 4 - Proiecte de Cercetare Exploratorie
PN-III-P4-ID-PCE-2016-0026 2017 - 2019

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://science.research.uaic.ro/nanotweez/index.html

Abstract:

Molecular recognition and binding mediated by weak noncovalent intermolecular interactions, play a pivotal role in many biological processes. Binding energy measurements rely on macroscopic approaches, each of which carries particular advantages and shortcomings. The advent of new approaches based on single-molecule protocols, e.g., optical tweezers, can complement the output of the macroscopic techniques, but still suffer from drawbacks with respect to achieving optimal and reproducible measuring conditions. As a new paradigm to studying molecular binding processes devoid of the drawbacks associated to existing techniques, we propose herein a single-molecule approach based on an -hemolysin (-HL) protein nanopore sensor, to explore, probe and quantify the bond energy of non-covalent molecular complexes. As a state-of-the-art approach and potential game-changer in the field of nanopore-based force spectroscopy, we will use the ‘nanopore tweezers’ technique developed in our lab, to capture and then reduce up to an almost stand-still of the escape rate of a tailor-functionalized biomolecule from a membrane immobilized -HL. We hypothesize that subsequent to its arrest inside the -HL, the unzipping of a dimeric biomolecule could be induced, and characterized experimentally in microscopic details. We set herein to develop the proof-of-concept approach for the single-molecule nanomechanics through applying controllable, oppositely oriented electric forces on a custom engineered, peptide-functionalized duplex biomolecule leading to its dissociation, and delivering in the end an estimate of the complex’s bond energy. To demonstrate the utility of this approach, we will apply it to investigate the Hg2+-mediated hybridization of natural DNA complexes with multiple T:T mismatched base pairs, well-known in its implications but far less studied in molecular details, with potential applications in nanotechnology as building block for self-assembling functional nanostructures.

Homogenous immunoassay technique based on functionalized nanoparticles. Application to detection of pesticide contaminant 2,4-dichlorophenoxyacetic acid from alimentary and environmental samples Call name: Joint Applied Research Projects - PCCA-2011 call, Type 1
PN-II-PT-PCCA-2011-3.1-0402 2012 - 2016

Role in this project: Partner team leader

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH

Project partners: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO); UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO); INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU TEHNOLOGII IZOTOPICE SI MOLECULARE I N C D T I M (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://proiecte.nipne.ro/pn2/138-proiecte.html

Abstract:

Immunological methods such as enzyme linked immunosorbent assay (ELISA) are increasingly becoming important for pesticides residual analysis due to the high specificity of detecting molecules like antibodies. These immunoassay methods are highly specific, sensitive (nanogram or picogram) and accuracy for the detection of low molecular weight contaminants presents in our environment. ELISA is a technique based on the ability of non-labeled antigen (e.g. pesticide) in a specific volume of standard solution or in an unknown sample to compete with a fixed of amount of enzymatic labeled antigen for a limited number of binding sites of a specific binding antibody protein. The objective of the project is to develop a new and innovative immunochemical technique based on functionalized nanoparticles, homogenous enzyme linked immunosorbent assay (HnELISA) technique for detection of pesticide contaminant 2,4-dichlorophenoxyacetic acid (2,4D) from alimentary and environmental samples. 2,4D is one of the most used herbicide in agriculture to control and destroy of the weeds that can affect agricultural crops. The remanence of this organochlorurate compound in alimentary products, transfer and contamination of ground water in the areas where this pesticide is used require the analysis of this chemical in order to establish the contamination level of the alimentary products and the environmental factors (water, soil).

The objective of the project is to develop an immunoassay technique with improved qualities in comparison with traditionally ELISA technique existed on the market for detection of pesticide contaminants from alimentary and environmental factors. Qualitative characteristics as sensitivity, accuracy, stability of the nanoimmunosorbent and low cost per assay are finally taken in account. Development of HnELISA technique would have practical application in monitoring of the pesticide contaminant 2,4D from alimentary and environmental samples.

Rational design and generation of synthetic, short antimicrobial peptides. Linking structure to function Call name: Joint Applied Research Projects - PCCA-2011 call, Type 1
PN-II-PT-PCCA-2011-3.1-0595 2012 - 2016

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO); INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU TEHNOLOGII IZOTOPICE SI MOLECULARE I N C D T I M (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO); UNIVERSITATEA BABES BOLYAI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.science.research.uaic.ro/biopep/

Abstract:

Antimicrobial peptides (AMPs) are an integral part of the immune system and protect a host from invading pathogenic bacteria. To overcome the problem of antimicrobial resistance, AMPs are being considered as potential alternatives for antibiotics. Although over 1000 AMPs have been isolated and characterized from various hosts, only limited successes have so far been achieved in clinical trials. The major hurdles for converting them into drugs lie in the high cost of production, toxicity to host cells, and susceptibility to proteolytic degradation. Therefore, a better understanding of the structure–activity relationships of AMPs is required to facilitate the design of novel antimicrobial agents. Herein we plan to focus our effort on designing and optimizing novel short, cationic amphiphilic peptides. We will undertake rational design, synthesis, and extensive testing of a series of short cationic peptides, we envision proteolityc and salt resistant. They will be made of a limited set of L- and D-aminoacids based on an elementary amphipathic templates of up to to 11 aminoacids, searching for the minimum number of aminoacids and optimal architecture able to confer the peptide optimal lytic activity and specificity against various pathogens. In order to enhance antimicrobial activity with no additional hemolytic activity, peptide synthesis will be considered by using non-natural amino acid analogs that will substitute hydrophobic residues leucine, isoleucine and phenylalanine. This group of peptides will be designed and synthesized with shorter sequence and simpler molecular structure and could be easily modified upon a particular requirement. The structural simplicity also offer technological advantages for mass production and purification.

Ion sensing and separation through modified cyclic peptides, cyclodextrins and protein pores Call name: Complex Exploratory Research Projects - PCCE-2011 call
PN-II-ID-PCCE-2011-2-0027 2012 - 2016

Role in this project:

Coordinating institution: “Alexandru Ioan Cuza” University

Project partners: “Alexandru Ioan Cuza” University (RO); National Research and Development Institute of Isotopic and Molecular Technologies (RO); “Babes-Bolyai” University (RO); “Horia Hulubei” National Institute for Physics and Nuclear Engineering (RO); “Carol Davila” University of Medicine and Pharmacy (RO)

Affiliation: “Alexandru Ioan Cuza” University (RO)

Project website: http://science.research.uaic.ro/biosens/

Abstract:

Development of nanostructures capable of detecting and separating individual molecules and ions has become an important field of research. Particularly, protein-based nanostructures are attractive due to their ability for tunable molecular recognition and ease of chemical modification, which are extremely important factors on various applications. In this project, self-assembly functionalization will be approached, aimed at providing an efficient design for molecular recognition, ion sensing and separation, through new host-guest chemical methodologies, bio-nanofabrication and physicochemical manipulations methods. New crown ether type macrocycles, functionalized cyclodextrins and cyclic peptides will be engineered to work as specific molecular adaptors for the -hemolysin protein, giving rise to hybrid molecular superstructures possessing ion sensing and selectivity properties. The size and functionality of the macrocycles are targeted to ensure the anchorage in the pores and the selectivity of specific host-guest complexation processes. A surface detector array device suitable for use with a biosensor is envisioned, through ink printing nanotechnologies. The device architecture will be formed of a substrate having a surface defining a plurality of distinct bilayer-compatible surface regions separated by one or more bilayer barrier regions. Custom designed nanoscale bilayers containing selected receptors through cyclodextrins derivatives and macrocyclic peptides, self-assembled on different micro-nano arrays surfaces (polymers, Au or Si) will be fabricated. Further engineering of such functionalized nanomaterials based on molecular recognition and host-guest methodologies, in conjunction with flexible and mechanically robust enough substrate platforms, have the great potential for applications such as separation of nanoparticles, sensors, drug delivery, removal of heavy metals from aqueous solutions and chiral separation.

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