BrainMap

Alexandra Farcas

Dr.

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

Researcher

Curriculum Vitae (05/07/2023)

Expertise & keywords

In silico optimization of CRISPR/Cas9-Gold nanovehicle design Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2019-0292 2020 - 2022

Role in this project: Project coordinator

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

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

Abstract:

CRISPR/Cas9 gene editing is a novel and versatile technology that correct disease-causing errors in the genomes, with multiple and broad applications in medical, agricultural and pharmaceutical industries. The major obstacle in implementing CRISPR/Cas9-based therapeutics is to develop nanovehicles that can target genetic mutations in a specific manner. Gold nanoparticles (GNP) functionalized with synthetic oligonucleotides combine the optoelectronic properties of the gold core with the particular properties of oligonucleotides, for instance selectivity and specificity. Furthermore, functionalized GNPs have been previously used in vivo for delivery of CRISPR/Cas9 to successfully repair gene mutations causing muscular dystrophy. However, prior to clinical applications, safe and efficient CRISPR/Cas9-Gold-based delivery vehicles should be designed based on a deep understanding of the underlying molecular mechanisms. In this proposal, we intend to computationally optimize such a design in two steps. First, we will optimize the DNA loading on a range of GNP sizes in nanoparticle-oligonucleotide conjugates. In the second stage, we will perform a thorough in silico investigation of GNP-oligonucleotide conjugates complexed with Cas9 ribonucleoprotein as delivery nanovehicles.

design of Highly Efficient AntimicrobiaL peptides: in Silico preDiction and Experimental validation Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2016-0032 2018 - 2020

Role in this project: Key expert

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

Project website: http://www.itim-cj.ro/PNCDI/te99/index.htm

Abstract:

Antimicrobial peptides are a type of host defense peptides that present both high therapeutic potential and high selectivity of interaction with bacterial cells over mammalian cells. However, the possibility of bacterial resistance occurring against natural AMPs activity, combined with the already picked low-hanging fruits of obvious natural peptide targets, suggests the need for novel AMP design approaches. The main challenge is increasing efficacy of the novel drugs in safety conditions, since previous individual design methods had only limited success thus far.

The main objective of this application is the development of a new approach on identifying potential novel antimicrobial drugs. The ground-breaking nature of the proposed approach is that it combines the predicting power of several complementary computer-aided design methods with experimental validation of the proposed AMPs. We will computationally design new AMPs whose purpose would be to disrupt or pass through membrane models, and experimentally validate their efficiency against several bacterial strains. This new approach, can, in principle, be applied to find novel AMPs and rank them by their computationally predicted relative antimicrobial activity and cytotoxicity.

Computational design of cationic polymers as gene delivery vectors Call name: P 4 - Proiecte de Cercetare Exploratorie
PN-III-P4-ID-PCE-2016-0474 2017 - 2019

Role in this project:

Coordinating institution: UNIVERSITATEA BABES BOLYAI

Project partners: UNIVERSITATEA BABES BOLYAI (RO)

Affiliation: UNIVERSITATEA BABES BOLYAI (RO)

Project website: http://www.phys.ubbcluj.ro/~tbeu/PolyGeneVec/

Abstract:

Polyethylenimine (PEI) shows one of the highest transfection efficiencies as a gene delivery vector, effectively protecting DNA from enzyme degradation. Its particular charge distribution is considered responsible for: (a) DNA condensation as PEI/DNA polyplexes (entering cells via endocytosis), (b) proton sponge effect of PEI (triggers release of polyplexes from endosome), and (c) DNA release from polyplexes (further processed inside the nucleus).

The major incentives of our interdisciplinary project, matching a H2020 high-priority research area, are the absence of a realistic force field (FF) for PEI and the high topicality of investigations regarding the role of PEI in DNA condensation.

The main objectives are:

O1. Developing a novel fine-grained (CHARMM) FF for protonated PEI, rigorously derived from high-quality ab initio calculations, using very recent software packages and technologies. We will define specific residues and optimize atomic charges, as well as bond, angle, and dihedral parameters.

O2. Fine-grained MD investigation of dynamic structuring of solvated PEI, in terms of gyration radius, end-to-end distance, persistence length, radial distribution functions, coordination, diffusion coefficients, and chain rigidity.

O3. Developing a novel coarse-grained (CG) (MARTINI) FF for protonated PEI, by mapping entire CHARMM residues to CG beads and adjusting their interaction parameters using as reference the atomistic FF and MD simulations. The CG simulations will use tenfold time steps for significantly larger solvated PEI systems.

O4. Fine- and coarse-grained MD investigations of DNA condensation aiming at enhanced efficiency of condensation/transfection processes. Using the developed CHARMM and MARTINI FFs, we will simulate DNA/PEI condensation under diverse conditions. Topological and energetic correlations of the charged interactions sites of DNA and PEI will corroborate the DNA size reduction to provide estimates for optimal protonation ratios of PEI.

Design of New Lipid-Modified Peptides to Destabilize Ras Nanoclusters - A Novel Therapeutic Approach for Targeting Oncogenic Ras Proteins Call name: Projects for Young Research Teams - RUTE -2014 call
PN-II-RU-TE-2014-4-2418 2015 - 2017

Role in this project: Key expert

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

Project website: http://www.itim-cj.ro/PNCDI/ru118/

Abstract:

Ras proteins mediate a wide variety of signal transduction pathways that regulate cell growth,proliferation and differentiation.These proteins are small GTPases acting as binary switches between the GDP-bound “off” and the GTP-bound “on” states.Oncogenic mutations of Ras renders them constitutively active and are associated with ~15% of all human cancers and up to 90% in specific tumors.Current strategies for developing drugs targeting Ras mutants had little success.Experiments and computer simulations alike showed that membrane-bound Ras proteins form nonoverlapping dynamic nano-sized subdomains (nanoclusters) in an activation state-/isoform-dependent manner.Nanoclusters are protein-lipid assemblies serving as exclusive sites for effector recruiting and signal activation.The main objective of this application is the development of a new approach on finding potential drugs against oncogene Ras.The ground-breaking nature of this approach is that it exploits the dynamic nature of Ras nanoclusters and the key role of their stability in signal transduction.We will computationally determine Ras self-association binding sites and their binding strengths.The results will be used to design new lipid-modified peptides(LMPs) which,due to their designed features,would disrupt Ras nanoclusters.Since Ras nanoclusters are highly dynamic in nature,the peptide-Ras interaction should disrupt nanocluster’s stability and hence the signal output.

Alkali and silver halides based magnetic tunnel junctions Call name: Exploratory Research Projects - PCE-2012 call
PN-II-ID-PCE-2012-4-0028 2013 - 2016

Role in this project: Key expert

Coordinating institution: UNIVERSITATEA BABES BOLYAI

Project partners: UNIVERSITATEA BABES BOLYAI (RO)

Affiliation: UNIVERSITATEA BABES BOLYAI (RO)

Project website: http://www.phys.ubbcluj.ro/~emil.burzo/rezultateo_ro.html

Abstract:

The research project is directed on the study of novel types of magnetic tunnelling junctions (MTJs) based on alkali halides and silver chloride. The magnetic tunnelling junctions from the systems Fe/NaCl-AgCl/Fe, Fe/NaBr/Fe, Fe/NaBr-AgBr/Fe, Fe/LiF/Fe, Fe/LiBr/Fe, M/NaCl/M and M/NaBr/M where M is a transition metal or an alloy as FeCo, FeNi or Co2MnSi will be considered. The studies involve determination of more stable interface structure, layer resolved charge transfer and magnetic moments, layer and atom resolved DOS, exchange coupling in heterostructures, FM and AFM conductances as function of spacer and electrode thickness, k||-resolved conductances of FM and AFM states and tunnelling magnetoresistances. The our preliminary results evidenced TMR ratio of 3000% in Fe/AgCl/Fe system and even more high in Fe/NaCl/Fe MTJ. The studies will contribute to development of new types of TMJs with possible high performances, i.e., high TMR ratios and low resistances, and can also direct the experimental researches in obtaining devices with feasible technical applications.

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