BrainMap

Mr. Mihai Radu

Dr

Senior Researcher (level 1) - INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH

Researcher | Scientific reviewer | Manager

Curriculum Vitae (06/03/2024)

Expertise & keywords

Network for Optimized Astatine labeled Radiopharmaceuticals - COST action CA19114 Call name:
2020 - 2024

Role in this project: Key expert

Coordinating institution: GIP ARRONAX

Project partners: GIP ARRONAX (); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH ()

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH ()

Project website:

Abstract:

Development of new strategies of DNA repair inhibitors induced radiosensitization of glioblastoma exposed to low and high linear transfer energy radiotherapy Call name: EEA Grants - Proiecte Colaborative de Cercetare
RO-NO-2019-0510 2021 - 2024

Role in this project: Key expert

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); OSLO Universitetssykehus HF (NO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Project website: https://www.doradios.dfvm.nipne.ro/

Abstract:

Glioblastoma is the most frequent and deadliest form of brain cancer and represents a major health problem affecting many young children. The median overall survival is limited to 12-18 months following diagnosis despite continuous improvements in treatment. Radiation therapy plays a crucial role in glioma treatment, however, glioma cells survive the treatment, one underlying reason being the presence of cancer stem cells that have high DNA repair capacity. One promising strategy to improve treatment of this agressive radioresistant tumor is therefore to combine radiotherapy with inhibitors of DNA repair. The present project aims to develop new efficient strategies for glioma radiosensitization. We aim at identifying radiation-drug combinations inhibiting DNA repair and exploring how such treatment combinations work in cells irradiated with high-LET versus low-LET radiotherapy (X-ray, protons and carbon-ions). We also aim at identifying new promising biomarkers signatures that may support the development of personalized treatment of patients. These biomarkers will be generated to match glioblastoma specific molecular signature for radiosensitivity.

An original approach will be employed by using a new DNA repair high-throughput drug screening, unique in the world, available at Norwegian partner, to identify drugs that could be used as glioma radiosensitizers in association with conventional low-LET and with high-LET particle therapy. The ideal glioma cancer stem cells model will be used. Moreover, after identifying the best promising candidate combination, we will perform a complex “omic” (transcriptomic, metabolomic, proteomic) analysis of the response of the tumor cells to the selected combination. This will allow us to yield the sensitivity signature of the tumor. The generated information will shed light on the drug-specific resistance mechanisms employed by tumoral cells. Thus, predictive biomarker libraries could be generated to match glioma specific molecular signature with a paramount importance for subsequent clinical trial design. This approach represents a potential helpful strategy that can lead to uncover new highly effective radiation-drug combinations that can be applied in future glioblastoma therapy. In the short term our results will identify new promising combinations of radiation and drugs to be tested in further preclinical studies and clinical trials. The results will open a new way to optimize the radiation therapy procedures allowing to choose the appropriate radiosensitizer for particular types of glioblastoma. In this way the project may contribute to a personalized approach, patient-centered, in curing this devastating type of cancer. In the long run we hope that the new combination treatment strategies can be applied in future proton/heavy ions radiotherapy. The society will benefit through the development of new and better strategies to treat cancer.

The expertise of the Romanian team will be highly enhanced in the topic of mechanisms driven the DNA repair following the radiotherapy procedure and how these can be modulated by appropriate drugs/radiation combinations. The outcome of the project will allow a good chance to develop new long-term collaborations with hospitals that could be end-users. The biological model used in the project, the revealed biomarkers will be exploited in the future research that will be run in the frame of bio-medical research planned at the new proton irradiation/ hadron therapy facilities provided by ELI-NP and help preparing the Norwegian researchers for exploiting a new proton radiotherapy centre (to be opened in 2023). Indeed, the proposed project will enhance the chances of higher performance of Romanian team in attaining international research project and to have a more active participation in the European Research Area. In particular, the project will be a solid basis for long-term strategic partnerships with research institutions from Norway.

Gamma radiation-modulated biotechnologies for application in bioeconomy Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0323 2018 - 2021

Role in this project: Project coordinator

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); INSTITUTUL DE BIOLOGIE (RO); UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO); INSTITUTUL DE CERCETARE - DEZVOLTARE PENTRU LEGUMICULTURA SI FLORICULTURA VIDRA (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU BIOTEHNOLOGII IN HORTICULTURA STEFANESTI-ARGES (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Project website: https://www.nipne.ro/proiecte/pn3/13-proiecte.html

Abstract:

The Bio-Gamma complex project proposes, in accordance with the PCCDI2017 program, the institutional development of a representative consortium dedicated to providing conditions for exploiting and improving partners' expertise in the field of gamma irradiation stimulation of bioactive compounds biosynthesis with applications in bioeconomy. Gamma rays-induced cellular stress is proved as a useful tool in manipulating secondary metabolite biosynthesis. By extracting and characterizing them, we can obtain useful compounds for the pharmaceutical, cosmetic, food and special materials industries. The proposed activities ensure the partners sustainable institutional development and the valorization of their expertise in products, patentable and transferable technologies to the economic end-users. The project targets especially markets with high dynamics, as the ones of food and dietary supplements, thus subserving the priority field of Bioeconomy. Thinking about gamma irradiation as a central pillar, the project is proposed by a consortium of five institutions with complementary expertise and recognized for their scientific performance (two national research institutes, an Romanian Academy institute, a university and a research institute) with a good regional spread: Bucharest, Ilfov, Giurgiu, Arges and Cluj. Two of the institutions are potentially relaunching, and one is a newly built infrastructure. The joint project agenda provides conditions for the development of a collaborative perspective among partners, with a positive impact especially on institutions with a potential for relaunching. Hiring young researchers and assisting them in training courses will lead to an increase in the human resource quality of all consortium members. Regarding the institutions with the potential for relaunching, it will increase the level of competence and competitiveness, ensuring a consistent institutional development in the future, at both scientific and managerial level.

Assessment of radiation environment in space using nuclear emulsion Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2016-2096 2017 - 2018

Role in this project: Partner team leader

Coordinating institution: INSTITUTUL DE STIINTE SPATIALE-FILIALA INFLPR

Project partners: INSTITUTUL DE STIINTE SPATIALE-FILIALA INFLPR (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Project website: http://www.spacescience.ro/projects/arene/

Abstract:

A new method is developed for determine dose and LET ( liniar energy transfer) evaluation ) on the BION M2 satellite using nuclear emulsion. The satellite is planned to be flown in 2019 at a 1000 km , which is the highest altutude at which a recoverable satellite was launched. The research is performed in the frame of a International collaboration, with the IFIN , the institute of nuclear physics of the Czeck Academy fo Science, Prague and the Joint Institute of Nuclear research, DUBNA, Russia. The radiation environment is composed of different particles of different energies. In order to evaluate the dose we will have to determine charge, mass and momentum fo particles, because the dose depends directly of these parameters. The track properties have to be analysed and the method to evaluate these properties will be elaborated. In order to perform such a complex task we will have to investigate the theoretical and experimental data that exists to the present time. The method will be elaborated using a stack of emulsion that was flown in 1972 in the frame of the Intergovernamental Intercosmos collaboration. We have in our laboratory a part of this stack very well preserved that can be used. A scanning for all heavy particles that enter the edge of emulsion sheets will be performed and their tracks will be followed through the stack. For this purpose a mask that will allow the identification of the coordinates of tracks will be produced using the most moder technology. We will investigate the interactions of fast particles and measure the energy of the primary track using angular ditribution ( at the KSM nuclear track microscope ) Thir charge will be evaluated by delta rays counting. A special attnetion will be given to slow heavy ions, because they produced the larger LET in materials. Their properties can be investigating by grain counting on the range starting from the end point in emulsion. After the evaluation of all properties we will evaluate the flux

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: Partner team leader

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

European network for development of electroporation-based technologies and treatments - COST action TD1104 Call name:
2012 - 2016

Role in this project: Partner team leader

Coordinating institution: University of Lubljana

Project partners: University of Lubljana (RO); UNIVERSITATEA DE MEDICINA SI FARMACIE "CAROL DAVILA" (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Affiliation: University of Lubljana (RO)

Project website: https://www.cost.eu/actions/TD1104/#tabs|Name:overview

Abstract:

Exposure of biological cells to a sufficiently strong external electric field results in increased permeability of cell membranes, referred to as electroporation. Since all types of cells (animal, plant and microorganisms) can be effectively electroporated, without addition of viral or chemical compounds, electroporation is considered to be a universal method and a platform technology. Electroporation has become a widely used technology applicable to e.g. cancer treatment, gene transfection, food and biomass processing, and microbial inactivation. However, despite significant progress of electroporation-based applications, there is a lack of coordination and interdisciplinary exchange of knowledge between researchers from different scientific domains. Thus, critical mass for new major breakthroughs is missing. This COST Action aims at: (i) providing necessary steps towards EU cooperation of science and technology to foster basic understanding of electroporation, (ii) improving communication between EU research groups, resulting in streamlining European R&D activities, and (iii) enabling further development of new and existing electroporation-based applications by integrating multidisciplinary research teams, as well as comprehensive training for Early-Stage Researchers (ESRs). Results of this COST Action will provide multiple societal, scientific, and technological benefits from improving existing electroporation-based applications and adding new ones in the field of medicine, biotechnology and environment preservation.

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: Partner team leader

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: “Horia Hulubei” National Institute for Physics and Nuclear Engineering (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.

Elucidation of mechanisms of interaction between selected cytotoxic peptides with tumor cells, and optimize their anti-tumor properties Call name:
62-061/2008 2008 - 2011

Role in this project: Partner team leader

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO); UNIVERSITATEA BUCURESTI (RO); SPITALUL CLINIC JUDETEAN DE URGENTA "SF. SPIRIDON" IASI (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO); INSTITUTUL DE BIOCHIMIE (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Project website: http://neurobiologie.ro/ro/47-romana/contracte-nationale/160-pncdi2-62-0612008

Abstract:

In ciuda progreselor facute in terapia cancerului, exista pe plan mondial un interes deosebit pentru dezvoltarea unor tehnici noi in acest sens, indeosebi pentru evitarea efectelor detrimentale asociate terapiilor curente, precum si a capacitatii celulelor tumorale de a dezvolta rezistenta fata de medicamentele existente. In acest proiect vom studia, utilizind tehnici multidisciplinare de electrofiziologie, biologie moleculara, fluorescenta si modelare moleculara, mecanismele prin care clase particulare de peptide citotoxice exercita efecte anti-tumorale. O atentie particulara va fi acordata dezvoltarii de protocoale experimentale si biosintezei unor peptide citotoxice cu efecte anti-tumorale imbunatatite din punct de vedere al selectivitatii si capacitatilor litice.

Supporting growth of neuronal extensions and formation of synapses with a multipoint optical tweezer Call name:
61-11/2007 2007 - 2010

Role in this project: Partner team leader

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "CAROL DAVILA"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "CAROL DAVILA" (RO); UNIVERSITATEA BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Project website:

Abstract:

Un proiect recent al echipei noastre, condus de Dr. Trifu Simona, medic psihiatru, a cistigat finatare

pe CNCSIS 2007 pentru realizarea de sinapse cu ajutorul laserului. Date recente (PNAS 2002,

NATURE 2002, SCIENCE 2002) arata posibilitatea de a creste prelungiri neuronale cu ajutorul

laserului, mecanisme de invatare si crestere a eficientei sinaptice (plasticitate sinaptica), precum si

posibilitatea de a urmarii si evalua activitatea electrica a neuronilor prin intermediul influxurilor de

calciu. Tratarea unitara a neuronilor si sinapselor va putea realiza sinapse intr-un mod predictibil si

reproductibil, dupa un design stabilit de experimentatori. Datorita faptului ca in acest proiect se doreste

obtinerea de drepturi de proprietate intelectuala brevetabila (cu autor si proprietar Banciu Daniel

Dumitru), CNCSIS a impus ca informatiile rezultate sa fie clasificate conform reglementarilor legale in

vigoare.

Pe aceasta baza se pot construi retele neuronale cu elemente oscilatorii complexe ce sa interfere

intre ele. Baza modularii acestor oscilatii este data de un neuron cu doua sinapse ce permite inhibitia

sau activarea functiei neuronale. Aceasta modulare este realizata de catre circuite oscilatorii ce contin

neuroni ce au fost transfectati cu material genetic pentru expresia de receptori specifici. Prin acest

circuit oscilant secundar se amplifica semnalul ce trebuie citit din biosensor.

Prin realizarea unei interfete de iesire ce sa contina o fibra musculara cuplata printr-o placa

neuromotorie la circuitul de oscilatie modulat, se simplifica modul de evaluare al activitatii neuronilor

transfectati. Initial aceasta citire se face prin intermediul microscopului, ulterior putindu-se simplifica in

faza de utilizare industriala (neinclusa in proiect).

Biosenzori trebuie ulterior calibrati in functie de liganzii specifici, de liganzi nespecifici, si in functie

de stabilitatea in timp. Dupa aceasta calibrare si caracterizare se evalueaza ce informatii sint

protejabile prin brevet, si se declasifica in vederea publicarii celelalte informatii.

Abordarea interdisciplinara si interinstitutionala se realizeaza prin indeplinirea unor activitati specifice

si integrate. Coordonatorul realizeaza sinapsele, circuitele oscilante si regulatorii si integreaza

rezultatele celorlalti parteneri in realizarea biosenzorilor cu drepturi de proprietate intelectuala,

inclusive activitati conexe, apartinind lui Banciu Daniel Dumitru.

Partenerul 1 realizeaza culturile neuronale primare, caracterizarea electrofiziologica a circuitelor

produse de coordinator si transfectia sinaptica. Modul in care transfectia sinaptica se integreaza in

circuitul mediatorilor secunzi neuronali si informatiile conexe sint drepturi de proprietate intelectuala

apartinind lui Amuzescu Bogdan.

Partenerul 2 evalueaza circuitele neuronale prin imagistica de Ca. Evalueaza eficienta transfectie si

caracterizeaza circuitele neuronale din punct de vedere al interactiei ligand-receptor.

Multifunctional platform for fluorescence microscopy and spectroscopy with electrophysiological and pharmacological applications in neuro-and cardiopatologies Call name:
Capacitati nr. 158/2008 2008 - 2010

Role in this project: Partner team leader

Coordinating institution: UNIVERSITATEA BUCURESTI

Project partners: UNIVERSITATEA BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Project website: http://neurobiologie.ro/ro/47-romana/contracte-nationale/164-pncdi2-capacitati-nr-1582008

Abstract:

Studiile de electrofiziologie reprezinta una din principalele modalitati de investigare a activitatii celulare, in

particular in cazul celulei nervoase. Insa in ultima decada, perfectionarea multor tehnici de microscopie de fluorescenta

a condus la aparitia unei modalitati complementare de investigare la nivel celular si molecular. Cele doua pachete de

tehnici (electrofiziologice si de fluorescenta) se completeaza reciproc privind rezultatele furnizate in invest igatiile in

vivo si in vitro. Rezultatele acestui gen de studii sunt esentiale pentru intelegerea mecanismelor moleculare si celulare la

nivelul sistemelor nervos si cardiovascular, in particular in cazul investigarii efectelor moleculelor cu potential

farmacologic. In acest sens, in laboratoarele performate din tarile dezvoltate s-a initiat in ultima decada implementarea

unor proiecte de infrastructura de tip platforma multifunctionala in cadrul careia sunt utilizate in mod complementar

metode de electrofiziologie si de fluorescenta cu scopul obtinerii unor performante mai ridicate in descrierea

fenomenelor la nivel celular si molecular. Astfel de platforme includ echipamentele standard de electrofiziologie

(instalatii de patch-clamp, voltage-clamp, etc.) si echipamente de investigatii bazate pe fluorescenta (spectrofluorimetre,

microscoape de fluorescenta de camp larg, microscoape confocale etc.). Din perspectiva tehnicilor de microsocopie de

fluorescenta, echipamentul cel mai important in jurul caruia se centraza o astfel de platforma este un microscop

confocal de inalta performanta. De multe ori pe microscopul confocal se monteaza si o instalatie de patch-clamp ceea

ce permite investigarea prin ambele metode a exact aceluiasi preparat biologic. Aceste laboratoare de biofizica

specializate trebuie sa lucreze impreuna cu laboratoare preparative pentru probele biologice de investigat (de ex.

laboratoare de culturi celulare). Datorita costurilor ridicate ale unei astfel de investitii, nu intotdeauna toate

echipamentele platformei sunt amplasate in aceeasi locatie, intrucat platforma poate rezulta si din utilizarea in comun in

mod coordonat a echipamentelor mai multor institutii.

In Romania, exista premisele pentru infiintarea unei astfel de platforme multifunctionale pentru microscopie de

fluorescenta cuplata cu electrofiziologie. Astfel la Universitatea din Bucuresti, Facultatea de Biologie, functioneaza

Baza cu Utilizatori Multipli – Centru de Neurobiologie si Fiziologie Moleculara (BCUM-NFM) care foloseste ca

principale metode de investigare tehnicile de electrofiziologie pe culturi celulare neuronale. In cadrul BCUM -NFM s-au

dezvoltat si unele aplicatii care folosesc microscopia de fluorescenta pentru investigarea probelor pe care se fac si

masuratori de electrofiziologie. La Institutul National de C&D pentru Fizica si Inginerie Nucleara Horia Hulubei (IFIN -

HH), Departamentul de Fizica Vietii si Mediului (DFVM) exista un laborator de spectroscopie si microscopie de

fluorescenta in cadrul caruia s-au pus la punct metodele specifice de baza si sunt in dezvoltare tehnici moderne de tipul

FCS (fluorescence correlation spectroscopy) si TIRF (total internal reflection fluorescence microscopy). Insa

performantele la nivelul investigatiilor pe culturi celulare sau pe tesut (inclusiv in vivo) sunt limitate de lipsa unui

microscop confocal de inalta performanta. Prin inalta performanta pentru microscopul confocal intelegem nu numai

niste parametrii de functionare performanti (rezolutie, achizitie, etc.) dar si posibilitatea de a putea dezvolta pe

echipamentul respectiv (prin adaugare de noi module si accesorii) si alte facilitati decat cele pe care le are la momentul

achizitiei (ex. microscopie multifotonica).

Obiectivul principal al acestui proiect este dezvoltarea capacitătilor de cercetare ale celor doua institutii implicate

(Universitatea din Bucuresti prin BCUM-NFM si IFIN-HH), cresterea competitivitatii lor cu accent pe deschiderea75

catre mediul stiintific international si pe obtinerea de infomatii utile in domeniul farmacologiei implicate in patologiile

sistemului nervos central si ale aparatului cardiovascular. Atingerea acestui obiectiv se realizeaza prin achizitia unui

microscop confocal de inalta performanta care va completa infrastructura celor doua institutii permitand astfel crearea

unei plaftorme multifunctionale de spectroscopie si microscopie de fluorescenta cu aplicatii electrofiziologice si

farmacologice in neuro- si cardiopatologii. Folosind microscopul confocal ne propunem sa dezvoltam in viitorul

apropiat tehnici de fluorescenta moderne (FCS, FRET, FLIM, microsocopie multifotonica) care sa fie folosite in paralel

cu cele electrofiziologice pe aceleasi preparate biologice. In acest scop pe microscopul confocal se va monta o instalatie

de patch-clamp. Necesitatea aparitiei unei astfel de platforme este sustinuta de impactul rezultatelor ce se pot obtine

prin cercetari coordonate folosind ambele pachete de tehnici experimentale in domeniul farmacologiei unor patologii cu

impact larg. Un argument important care sustine acesta initiativa este buna colaborare dintre cele doua institutii si

dorinta comuna de a promova expertiza romaneasca in proiecte de cercetare internationale utilizand o infrastructu ra cu

performante deosebite.

Neuropathic pain mechanisms in transgenic mice with type I diabetes Call name:
41-074 / 18.09.2007 2007 - 2010

Role in this project: Partner team leader

Coordinating institution: UNIVERSITATEA BUCURESTI

Project partners: UNIVERSITATEA BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Project website: http://neurobiologie.ro/ro/47-romana/contracte-nationale/159-pncdi2-41-0742007

Abstract:

Durerea neuropatica este cea mai comuna forma de neuropatie periferica, afectand 30-60% dintre pacientii diabetici. Cele mai comune neuropatii periferice sunt cele senzoriale, in care pacientii prezinta o disfunctie a perceptiei senzoriale. In ciuda acestor date clinice, mecanismele moleculare ale neuropatiei diabetice raman inca neclare. In studiile din literatura, modelul cel mai des utilizat de soarece/sobolan diabetic este cel indus prin injectare cu streptozotocina. Studiul nostru are avantajul utilizarii unui model unic dezvoltat de Institutul Cantacuzino: soarecele dublu transgenic TCR-HA+/-/Ins-HA+/- (dTg). Scopul proiectului este a identifica mecanismele moleculare ale durerii neuropatice pe baza studiilor de electrofiziologie, imunologie, imunofluorescenta si de comportament animal utilizand un model de soarece dublutransgenic cu diabet de tip I. Metodele electrofiziologice si de imunofluorecenta vor viza o gama larga de receptori membranari (familia TRPV) si canale ionice (familia Nav si familia ASIC) cu posibile implicari in mecanismul durerii neuropatice. Studii comportamentale (determinarea pragului de durere la stimuli termici, mecanici, si chimici, detectarea hiperalgeziei si alodiniei; investigatii senzori-motorii, cognitive si exploratorii) si cele sistemice (parametri imunologici celulari si biochimici) vor intregi tabloul clinic si vor valida modelul de soarece pentru diabetul de tip I. In finalul studiului ne propunem testarea unor analgezice naturale (i.e flavonoide: quercetina, curcumina etc.) pe modelul ales, si estimarea potentei lor in reducerea neuropatiei diabetice prin intreaga baterie de teste anterior dezvoltate. Proiectul este de mare complexitate, iar echipele implicate in realizarea sa au o vasta experienta recunoscuta pe plan national si international. Impactul clinic al acestui proiect este extrem de important, studiul constituindu-se intr-o etapa preclinica de elucidare si posibil tratament al neuropatiei diabetice.

Molecular characterization of mechanisms of action of antimicrobial peptides and de novo prediction of molecular structures with high antimicrobial potential Call name:
PNCDI2 61-016/2007 2007 - 2009

Role in this project: Project coordinator

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 BUCURESTI (RO); UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Project website: http://proiecte.nipne.ro/pn2/50-proiecte.html

Abstract:

Una din preocuparile majore ale cercetarilor in domeniul stiintelor vietii (sanatatii in particular) o reprezinta gasirea unor noi mijloace de a potenta apararea organismului contra agentilor patogeni. O cale foarte promitatoare este producerea unor medicamente bazate pe peptide antimicrobiene (anti-microbial peptides - AMPs). AMPs reprezinta o clasa de peptide mici (max 10 kDa) care au capacitatea de a distruge agenti patogeni de origine microbiana si virala. Mecanismele de actiune sunt cunoscute doar partial si pentru un numar mic de AMPs, iar in general se considera ca actiunea toxica a AMPs se bazeaza pe inducerea de catre aceste molecule in membrana externa a agentului patogen a unor pori aposi ce faciliteaza transferul nespecific al ionilor, ce conduce in final la lizarea celulei-tinta. In cadrul proiectului ne propunem o investigare multidisciplinara a mecanismelor de actiune a AMPs, obiectivele majore fiind: (1) selectia acelui tip de AMPs care produce o eficienta maxima antimicrobiana in conditiile unor efecte secundare minime, (2) analiza factorilor care influenteaza mecanismul de actiune al AMPs la nivelul membranei celulare si corelarea acestora cu eficienta AMPs si (3) predictia unor structuri noi de AMPs cu eficienta sporita. Activitatile proiectului se vor desfasura pe cateva directii: (a) studierea efectelor antimicrobiene, citotoxice (pe celule de provenienta umana si animala) si moleculare (studii electrofiziologice) ale unei clase de AMPs, cu selectia moleculelor cu eficienta maxima si citotoxicitate minima, (b) analiza interactiunii AMPs cu membranele lipidice model si naturale si gasirea acelor parametri fizico-chimici care pot influenta eficienta actiunii AMPs (c) modelarea moleculara a structurii AMPs selectate si predictia, pe baza modificarilor induse in structura primara a AMPs selectat, a unor noi structuri cu eficienta imbunatatita. Proiectul este propus de trei institutii cu expertiza in domeniu: IFIN-HH, Universitatea Bucuresti si Universitatea Al. I. Cuza. In cadrul proiectului se va folosi o varietate larga de tehnici: culturi celulare eucariote si procariote, metode de electrofiziologie, metode bazate pe fluorescenta si tehnici de modelare moleculara.

Study of mechanisms involved in antibiotic resistance in Gram-negative bacteria impermeability on natural and reconstituted membranes Call name:
168 / 01.09.2006 2006 - 2008

Role in this project: Project coordinator

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

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Project website: http://proiecte.nipne.ro/ceex/43-proiecte.html

Abstract:

Rezistenta la antiobice este o problema clinica extrem de des intalnita in tratamentul bolillor infectioase. Solutiile la problematica rezistentei antimicrobiene nu pot sa rezulte decat din intelegerea mecanismelor care stau la baza aparitiei acesteia. In acest sens numeroase tentative experimentale din literatura de specialitate se canalizeaza pe studii genetice asupra tulpinilor bacteriene. Propunerea de proiect abordeaza rezistenta la antibiotice prin studiul mecanismelor moleculare ale penetrarii antibioticelor betalactamice (ceftazidima) si floroquinolonelor (ciprofloxacina) prin membrana externa a bacteriilor Gram-negative. Abordarea tehnica a proiectului implica atat metode experimentale (tehnici de electrofiziologie, tehnici de fluorescenta, metode de realizare a membranelor lipidice model, metode de caracterizare fenotipica si moleculara a tulpinilor bacteriene) cat si de simulare moleculara (metoda de dinamica browniana, chimie computationala etc.). Anticipam ca studiile vor conduce la descrierea detaliata a procesului de transport a ceftazidimei/ciprofloxacinei printr-o porina din membrana externa a E coli (OmpF) si la caracterizarea rolului lipopolizaharidelor in membrana bacteriana, contribuind la intelegerea mecanismelor de rezistenta la antibiotice prin impermeabilitate. De asemenea, prin chimie computationala vor fi realizate predictii de structura pentru noi compusi cu rol antimicrobian. Expertiza stiintifico-tehnica a membrilor consortiului certifica viabilitatea propunerii de proiect si deschide calea integrarii intr-o retea europeana de profil.

Multi-parametric characterization of food safety – analytical and toxicological methods Call name:
6 / 03.10.2005 2005 - 2008

Role in this project: Project coordinator

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); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE CHIMICO - FARMACEUTICA - I.C.C.F. BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA MATERIALELOR BUCURESTI RA (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Project website: http://proiecte.nipne.ro/ceex/42-proiecte.html

Abstract:

e Cercetare Dezvoltare pentru Fizica si Inginerie Nucleara � Horia Hulubei � - IFIN-HH si parteneri: Institutul National de Cercetare Dezvoltare Chimico-Farmaceutica � INCDCF-ICCF si Institutul National de Cercetare Dezvoltare pentru Fizica Materialelor - INCDFM) cu scopul atingerii masei critice necesare pentru realizarea activitatii de cercetare � dezvoltare in domeniul securitatii alimentelor iradiate.

Existenta unei echipe interdisciplinare competitive pentru aceasta arie tematica (2.2, alimentatie, sanatate si buna stare) asigura desfasurarea unei activitati de cercetare cu sanse de succes in realizarea de colaborari intenationale (in cadrul PC7). Toxicitatea alimentelor iradiate este inca un subiect controversat in comunitatea stiintifica internationala. In cadrul proiectului ne propunem realizarea unor experimente in vivo si in vitro privind toxicitatea alimentelor iradiate. Experimentele in vitro vor fi efectuate pe culturi celulare iar cele in vivo pe animale de cultura. Experimentele in vivo vor viza toxicitatea cronica a alimentelor iradiate. Toxicitatea va fi studiata folosind teste de citotoxicitate, clinice, hematologice, biochimice si histologice.

Reteaua propusa asigura existenta in tara a expertizei necesare pentru abordarea tematicii alimentelor iradiate. Departamentul IRASM din cadrul IFIN-HH a facut pasi importanti in dezvoltarea metodelor necesare caracterizarii alimentelor iradiate (laborator de microbiologie acreditat, certificare internationala a sistemului de management, echipamente necesare dezvoltarii metodelor specifice de caracterizare). Mai este insa necesara perfectionarea unor metode pentru a avea la dispozitie un pachet de tehnici compatibil cu ceea ce se utilizeaza in laboratoare similare din UE. In cadrul proiectului se vor derula activitati de cercetare aplicativa pentru dezvoltarea unor metode (termoluminescenta, gaz-cromatografie, HPLC) care sa completeze setul existent de tehnici. Semnalarea in literatura de specialitate a aparitiei unor efecte sinergice ale produsilor chimici de iradiere in prezenta unor substante chimice cancerigene a condus la ideea adaugarii unor teste (micotoxine, hormoni de crestere si izotopi radioactivi) la setul standard de teste folosite pentru detectia alimentelor (caracterizare multiparametrica).

Nanoscopic investigations of interactions between biomembrane, bacterial toxins and proteins involved in the transfer of antibacterial agents in biomembrane Call name:
CEEX 2-Cex06-11-49/2006 2006 - 2008

Role in this project: Partner team leader

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO); UNIVERSITATEA BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Project website:

Abstract:

In ultimii ani, o multitudine de experimente de biologie celulara si biochimie au contribuit la modificarea modelului de membrana biologica a lui Singer si Nicholson in unul mai complex, in care lipidele au si roluri functionale si care are la baza microdomeniile lipidice (‘lipid rafts’). Structura si proprietatile acestor microdomenii lipidice, impreuna cu proprietatile electrice ale biomembranelor, reprezinta factori esentiali ce moduleaza interactiunea membranelor cu diferite proteine, procesele de difuzie laterala, specificitatea ligand-receptor, dinamica de conformatie a unor proteine membranare si proprietatile canalelor ionice. O clasa particulara de proteine, si anume toxinele bacteriene ce genereaza pori transmembranari cu structura secundara planara de tip  (-CFTs) reprezinta una din cele mai prolifice clase de proteine implicate in patogeneza bacteriana. In acest proiect ne propunem sa abordam din perspectiva complementara o tema extrem de interesanta, si anume mecanismele prin care alterari controlabile de structura biochimica membranara si anumiti factori fizici exogeni, moduleaza atit activitatea unor toxine bacteriene din clasa -CFT, cit si procesele de permeatie a moleculelor mici (de tipul antibioticelor) prin membrane artificiale cu structura asemanatoare celor naturale. Pentru prima parte a acestui proiect, ca model proteic functional pentru toxinele bacteriene din clasa -CFT, vom utiliza proteina alfa-hemolizina (HL). Ea va fi folosita pentru a studia la nivel de singura molecula insertia si oligomerizarea sa in membrane lipidice artificiale si naturale, in conditii ce mimeaza alterarile biochimice membranare ce pot fi asimilate cu diferite stari fiziologice celulare. In mod complementar, pentru a contribui la elaborarea de strategii mai eficiente pentru combaterea infectiilor bacteriene Gram-negative ce pot avea drept cauza exocitoza toxinelor din clasa -CFTs, vom studia mecanismele prin care valoarea pH-ului solutiei fiziologice, concentratia diferitilor ioni anorganici, compozitia biochimica membranara si proprietatile electrice ale membranelor altereaza proprietatile de permeatie prin porinele considerate a moleculelor din clasa antibioticelor. Acest proiect isi propune sa ofere solutii la urmatoarele problematici : (a) elucidarea, la nivel de singura molecula, a proceselor de insertie membranara si de transport ionic prin toxine bacteriene ce formeaza pori membranari, in conditii de alterare controlata a compozitiei lipidice membranare si (b) elucidarea mecanismelor moleculare prin care pH-ul si compozitia ionica a solutiilor fiziologice altereaza proprietatile fizice si chimice membranare, si ulterior proprietatile de transport macromolecular al unor porini specifici prezenti in membrana externa a bacteriilor Gram-negative. Asemenea studii pot contribui semnificativ la elaborarea de strategii de tratare a infectiilor bacteriene, asimilate cu exocitoza proteinelor din clasa -CFT, prin identificarea conditiilor optime de difuzie in spatiul periplasmatic a moleculelor de antibiotice. Interdisciplinaritatea acestui proiect este asigurata de contributia complementara a unor tehnici de investigare electrofiziologice, de modelare moleculara si imagistica spectroscopica.

Effects of combined exposure to the environment factors (ionizing and non-ionizing radiation, toxic chemical factors Call name:
Collaborative Agreement between Romanian Government and Hungaria 2006 - 2007

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); Frederic Joliot-Curie National Research Institute for Radiobiology and Radiohygiene (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO)

Project website:

Abstract:

Effects of oxidative stress induced by ionized radiations on model membranes Call name:
Program CERES-competitia 4-379 2004 - 2006

Role in this project: Project coordinator

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 ()

Affiliation: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH ()

Project website:

Abstract:

In cadrul acestui proiect ne propunem studiul efectului produs de stresul oxidativ, rezultat ca urmare a expunerii celulelor biologice la actiunea radiatiilor ionizante, asupra unuia dintre procesele principale in care sunt implicate membranele biologice si anume transportul membranar. Principalele aspecte specifice membranelor celulare avute in vedere in cadrul acestui studiu sunt transportul ionic si starea bistratului lipidic. Pentru a detalia mecanismul actiunii factorilor care genereaza stres oxidativ la nivelul membranei ne-am propus studierea fenomenului atat prin experimente efectuate pe membrane model (lipozomi unilamelari si bistraturi lipidice plane) cat si pe membrane biologice naturale. De asemenea am considerat necesara investigarea influentei radicalilor liberi atat asupra componentei lipidice cat si asupra celei proteice.

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