BrainMap

Norica Beatrice Nichita

- INSTITUTUL DE BIOCHIMIE

Researcher | Teaching staff | Scientific reviewer

Expertise & keywords

Next Generation Viral Hepatitis B and C vaccine development in plants and algae using advanced biotechnological tools Call name: EEA Grants - Proiecte Colaborative de Cercetare
EEA-RO-NO-2018-0078 2019 - 2024

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO); Norwegian Institute of Bioeconomy Research (NO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO); Center for Infection & Immunity of Lille (FR)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: https://www.smartvac.ro

Abstract:

Hepatitis B (HBV) and C viruses (HCV) infect the human liver, triggering persistent inflammation and eventually cirrhosis and hepatocellular carcinoma (HCC), the second leading cause of cancer-related mortality worldwide. Currently, more than 500 million people are chronically infected with HBV or HCV and at high risk of developing end stage liver disease and HCC. Collectively, HBV and HCV infections are responsible for about 1.3 million deaths annually. HBV infection is not curable with the treatment available today due to the nuclear replication form not being eliminated from infected hepatocytes. There is no doubt that vaccination remains the most effective strategy to limit HBV spreading and control the disease. Administration of the standard recombinant vaccine containing the small (S) HBV envelope protein produced in yeast (the HBsAg) had a major impact on HBV-related liver disease and death. Unfortunately, about 10% of vaccinated people do not develop protective antibody titers and remain vulnerable to infection. Moreover, the duration of the immunity conferred by the 3-dose intramuscular administration of the HBsAg is unclear, several studies indicating that administration of booster doses might be needed at 15 years post primary vaccination. A strategy to overcome these issues has considered the development of improved adjuvants. Other approaches have investigated the possibility to incorporate the more immunogenic middle (M) and large (L) HBV envelope proteins in the standard vaccine. However, the high costs associated with expression of these proteins in mammalian cells prevented the widespread use of the novel generation of HBV vaccines.

In the case of HCV, innovative direct acting antiviral cocktails which can achieve sustained virological response in more than 90% of treated patients have considerably advanced current therapy. Despite this success, the high treatment costs, the emergence of resistant mutants and the susceptibility to reinfection, underline the urgency for the development of a protective HCV vaccine that is still missing. Early clinical trials are ongoing for prophylactic B and T-cell based vaccines. A vaccine formulation based on HCV envelope proteins E1E2 heterodimer elicited cross-neutralizing antibodies in a minority of immunized patients despite its efficacy in animals. Although there is proof of concept in humans that HCV vaccination is possible, the design of the ideal antigen able to trigger protective immune response across HCV genotypes remains a major scientific challenge in the field.

The ultimate goal of prophylactic treatment in HBV and HCV infection is virus eradication, which can be achieved by conducting universal vaccination programs. However, these programs are financially very challenging and most low-income countries, which are confronted with the highest rates of infection, cannot afford them. Production of cost-effective vaccines would alleviate the economic burden on public health systems and increase availability to vulnerable societies.

In this context, our project proposal aims to: a) build upon our experience and knowledge accumulated in our previous collaboration on plant expression of HBV/HCV proteins (GreenVac project 2014-2017 funded by the EEA Norway-Romania Program) and produce high yields of novel HBV/HCV antigens with superior immunogenic properties based on innovative molecular design; b) take this experience a step forward and establish in premiere an advanced biotechnological platform for production of HBV/HCV antigens in algae; c) take advantage of the multiple recombinant protein expression systems developed in the consortium and perform systematic, comparative characterization of the biochemical and functional properties of the new antigens in relation to their immunogenicity; d) develop institutional networking around innovative plant and microalgae biotechnologies and train human resources in protein science in applied research in Romania and Norway.

Molecular mechanisms of insulin secretion in the presence of ER-stress induced proteins Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2019-1036 2020 - 2022

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: https://alexpety.wixsite.com/er-diab

Abstract:

Abstract

Pancreatic beta cells secrete insulin as a response to rises in blood glucose. Using INS-1 cells I identified EDEM1 as a critical signal for glucose-stimulated insulin secretion. EDEM1 is an endoplasmic reticulum (ER)-stress induced protein that targets misfolded glycoproteins for ER-associated degradation (ERAD). I demonstrated that overexpression of EDEM1 in beta cells accelerates ERAD, reduces the ER stress and facilitates proinsulin folding. In these cells, proinsulin released from the ER engages in a committed route towards the secretory vesicles, with an efficient conversion to insulin and secretion upon glucose-stimulation. Similarly, intact human islets transduced with EDEM1 released, on the average, twice as much insulin. This investigation showed that overexpression of EDEM1 can ameliorate beta cell function and support EDEM1 as potential target for the treatment of diabetes. The project aim is to investigate the molecular mechanism by which EDEM1 increases insulin secretion in pancreatic beta cells and to transfer these results into a method that can be applied into the clinical trials, to humans as potential treatement of diabetes mellitus. This will allow the development of a new method to treat diabetes mellitus using CRISPR Knock-In method designed to improve the physiology of the pancreatic cell.

Investigation of molecular mechanisms involved in HBV-associated lymphoproliferative diseases Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2019-1132 2020 - 2022

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: https://lymphohbv.wordpress.com/

Abstract:

Non-Hodgkin lymphomas (NHLs) are heterogeneous malignancies of lymphocytes ranked as the 5th to 9th most common cancer worldwide, more than 510,000 new cases being reported in 2018. The most common subtype is diffuse large B-cell lymphoma (DLBCL), accounting for about 40% of all NHL cases. In addition to genetic or environmental factors, NHL development is attributed to several viral infections such as Epstein-Barr-Virus, Human herpesvirus 8, Human Immunodeficiency Virus, Hepatitis C Virus and Human T-lymphotropic virus. Recent epidemiological studies have shown an increased risk for NHL development in hepatitis B virus (HBV) - infected patients. Moreover, these patients are more difficult to treat and their survival rate is lower, as compared with non-infected individuals. However, the mechanistic relationship between HBV infection and lymphoid cancer is not known. In this context, the current project proposal aims to investigate in premiere a possible etiological role of HBV in lymphomagenesis and decipher the consequences of lymphocytes exposure to HBV at molecular level. By using state-of the art methodologies we will investigate (a) the ability of lymphocytes to sustain productive HBV replication and (b) modulation of cellular signaling pathways by HBV in lymphocytes, such as the ER stress and unfolded protein response, activation of inflammation and upregulation of mutagenic enzymes. The results obtained in this study are expected to have an impact well beyond the project’s life span, by advancing new molecular targets that could be exploited in the future to develop more efficient therapeutic strategies to address this complex disease.

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: INSTITUTUL DE BIOCHIMIE (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.

Strengthening the capacity in translational research: vaccine development from concept to preclinical evaluation Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0529 2018 - 2021

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO”

Project partners: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO); INSTITUTUL DE BIOCHIMIE (RO); UNIVERSITATEA PENTRU STIINŢELE VIEŢII "ION IONESCU DE LA BRAD" DIN IAŞI (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE CHIMICO - FARMACEUTICA - I.C.C.F. BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE IN DOMENIUL PATOLOGIEI SI STIINTELOR BIOMEDICALE "VICTOR BABES" (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://www.convac.ro

Abstract:

Benefits of vaccination are indisputable, at both individual and social levels. As a major strategic direction in public health, vaccination makes these benefits far outweighing individual protection against many infectious diseases by eliminating / eradicating / reducing morbidity and complications associated with infectious diseases.

However, even if the benefits of vaccination are evident in modern society where unfiltered information leads to lower confidence in the vaccine, scientific arguments need to be continually put forward to demonstrate the efficacy, safety of vaccines, and to improve the concepts of their use. Also, the current tendency to use a limited number of antigens in existing vaccines on the market may lead to a vaccine pressure limited to a subset of microorganisms which may generate an antigenic drift of circulating microorganisms and, consequently, reduce protection. It is therefore necessary to continuously develop new antigens and the reduced antigenicity of some microbial components requires the presence of suitable adjuvants in current formulations of vaccines available on the market.

This consortium provides the necessary framework for the development of the vaccine through studies involving better characterization of the antigen, optimization of its formulation, extension of the immunogenicity characterization modalities, evaluation of the protection and finally elaboration of non-clinical studies documentation according to pharmaceutical regulations, aiming at increasing and consolidating scientific performance in the field of vaccination.

In addition, the consortium's objectives will include the development and consolidation of laboratory animal model studies completed with an accredited research-development service and the expansion of scientific expertise in vaccine science through the training and specialization of young researchers.

From the classical nutrition to precise nutrition in animal production, scientific basis for the nutrition security of the population Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0473 2018 - 2021

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU BIOLOGIE SI NUTRITIE ANIMALA - IBNA BALOTESTI

Project partners: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU BIOLOGIE SI NUTRITIE ANIMALA - IBNA BALOTESTI (RO); UNIVERSITATEA BUCURESTI (RO); UNIVERSITATEA BABES BOLYAI (RO); INSTITUTUL DE BIOCHIMIE (RO); UNIVERSITATEA "ŞTEFAN CEL MARE" DIN SUCEAVA (RO); UNIVERSITATEA DE STIINTE AGRICOLE SI MEDICINA VETERINARA CLUJ-NAPOCA (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://www.ibna.ro/proiecte-de-cercetare/item/110-pn-iii-p1-1-2-pccdi-2017-0473

Abstract:

The overall objective of the project is to strengthen the institutional capacity of IBNA by developing new research directions based on „omics” technologies – nutrigenomics, toxicogenomics, proteomics, metabolomics – and to relaunch the Laboratory of Biotechnology. This will generate a set of innovative outcomes in animal nutrition. The innovative aspects of the project include: use of agro-food wastes as adsorption and detoxifying agents for feed contaminants; testing the effect of phytoadditives (plants or plant extracts not yet used for such purposes) as antibiotic replacers (willow bark extracts) on the interaction between the intestinal tract physiology and the intestinal microflora; investigation of several less characterized and used protein-oleaginous sources (cowpea, Jerusalem artichoke, etc.); in vitro experimental models to evaluate the decontaminating potential of wastes under conditions of concurrent fungal, viral and microbial contamination; development of new feeding products which ensure a more efficient use of the protein in ruminants.

The project covers three regions of development and the partners are prestigious institutions, with complementary infrastructure and expertise, with converging scientific interests. The consolidation of new directions will enhance, both for IBNA (the relaunched institution), and for its partners, their capacity of applying for/running research projects, allowing studies with a high level of complexity, which generate practical results, relevant for the development of the animal production sector.

The project will impact on the human resources, the budget allowing the employment of 14 researchers (of which 10 by IBNA), whose specialisation is already ensured; it will also support the enhancement of the scientific expertise of the senior researchers by using vouchers. The training periods will enrich the portfolio of methods and techniques that can be applied for the directions in which IBNA aims to develop/relaunch.

Nanostructured azo-polymer films used as supports for cell cultures Call name: P 4 - Proiecte de Cercetare Exploratorie
PN-III-P4-ID-PCE-2016-0508 2017 - 2019

Role in this project:

Coordinating institution: UNIVERSITATEA TEHNICĂ "GHEORGHE ASACHI" IAŞI

Project partners: UNIVERSITATEA TEHNICĂ "GHEORGHE ASACHI" IAŞI (RO)

Affiliation: UNIVERSITATEA TEHNICĂ "GHEORGHE ASACHI" IAŞI (RO)

Project website: http://www.cercetare.icpm.tuiasi.ro/proiecte/azonanosurf/

Abstract:

The subject of the present proposal has a strong interdisciplinary character, being situated at the interface between chemistry, physics and biology. The main research direction will be focused on the interactions between the surface relief profile of the cells substrate and the cells response (cell fate) to the mechanical signals induced by the substrate. In the last period more and more biological studies were dedicated to this problem, especially in the case of stem cells, taking into consideration the possibility of cells differentiation using only mechanical signals. In the tissue engineering this type of interactions between the substrate and the cells will be decisive for the fabrication of smart biomaterials. Ideal candidates for new types of cells’ supports are the azo-polymers, because in their case one can change the film surface configuration, elasticity, or other mechanical parameters using only the light as external stimulus. All the other external stimuli usually used for the modification of the mechanical properties of a material (pH, temperature, salts concentration etc.) will affect the cell function making difficult to understand the cells’ response. In the case of azo-polymers, using a polarized laser source one can generate surface relief gratings on the film surface. The geometrical parameters of the gratings (amplitude and periodicity) can be very well controlled through laser operational conditions. Different chemical structure of the azo-groups will be synthesized in order to evaluate the cells adhesion capacity and the cells fate, as a function of the relief characteristics. More of than the surface relief type (grating or islands) can be changed in contact with water, creating so-called dynamic surfaces.

Human lactoferrin-derived peptides with broad spectrum antiviral activity Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2016-1409 2017 - 2018

Role in this project: Key expert

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website: http://peptivir.ucoz.ro/

Abstract:

Infections with Hepatitis B (HBV) and C viruses (HCV) are major public health threats with more than 400 million individuals being affected worldwide. Romania has a high prevalence of chronic infections, above the average of EU countries. Chronic patients are at high risk of developing end-stage liver diseases or hepatocarcinoma, and about 1 million people die annually due to such liver complications. Infections with the ubiquitous human pathogens Herpes simplex viruses (HSV) and the highly variable RNA viruses, Human adenovirus 5 (Ad5), Vesicular stomatitis virus (VSV), Enteric cytopathic human orphan 30 (ECHO subtype 30), Measles virus (MeV) also result in severe symptoms which require prolonged treatment.

A major drawback of the current antiviral therapies is the very high cost, which makes them unaffordable for many health care systems in developing countries.

Lactoferrin (Lf), an immunomodulatory glycoprotein was shown to interfere with the life-cycles of many viruses, regardless their origin or structure, both, in vitro and in vivo. In most cases, Lf was demonstrated to exert its antiviral effect at an early step of viral infection due to the crucial presence of cationic clusters in its structure. Recently, our group has rationally designed and characterized the anti-HBV activity of an Lf-derived peptide containing one of the cationic clusters. The peptide has better properties than the parental protein which could overcome the limitation for Lf use in clinical application. Thus, the major goal of this project is to take our initial observation further and investigate Lf-derived peptide(s) with increased solubility and efficient anti-viral action against a broad-range of human viruses, considering the pathogens listed above as models.

This project will prove the concept that the development of non-toxic, small Lf-derived molecule(s) with a broad-spectrum anti-viral activity may constitute a valuable, cheaper alternative to the current standard of care.

Call name: Premierea obtinerii atestatului de abilitare - Competitia 2015
PN-II-RU-ABIL-2015-2-0151 2015 -

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website:

Abstract:

DEVELOPMENT OF A COST EFFECTIVE ROMANIA-NORWAY JOINT PLANT-BASED TECHNOLOGY PLATFORM FOR PRODUCTION OF VACCINES AGAINST HUMAN HEPATITIS VIRUSES B (HBV) AND C (HCV) Call name: EEA Research Programme under EEA Financial Mechanism 2009-2014
EEA-JRP-RO-NO-2013-1-0022 2013 -

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO); Norwegian Institute for Agricultural & Environmental Research (Bioforsk) (NO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU MICROBIOLOGIE SI IMUNOLOGIE "CANTACUZINO" (RO); INSTITUTUL NATIONAL DE BOLI INFECTIOASE ''PROF.DR.MATEI BALS'' (RO); Center for Infection & Immunity of Lille (FR)

Affiliation: INSTITUTUL DE BIOCHIMIE (RO)

Project website:

Abstract:

This GreenVac research proposal aims to contribute to sustainable improvements in health of vulnerable social groups in Romania, in accordance with the health-related millennium development goals (MDGs) of the United Nation. It is also highly relevant to the EEA Research Programme between Romania and Norway where health is one of the four prioritized thematic areas.

Hepatitis B (HBV) and C viruses (HCV) are important human pathogens resulting in more than 500 million people being currently carriers. Chronically infected patients are at high risk to develop severe liver diseases, such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCC is one of the most frequent forms of cancer in humans and a fast progressing disease with a very high mortality rate, less than 5% of diagnosed patients surviving for up to 5-years (1). Most of these cases occur in developing countries resulting in widespread social and economic problems, especially among the poor people. Sadly, Romania has the highest prevalence of HBV/HCV infections among the EU countries (up to 7% of the population).

Current therapies against HBV/HCV, based on replication inhibitors and immune system activators are associated with severe side effects, resulting frequently in early discontinuation of treatment. In addition, both viruses are prone to development of resistance to antiviral inhibitors, which reduces significantly the efficiency of treatment (2).

Efficient anti- HBV vaccines are available on market; however, the costs associated with their production, the lack of appropriate distribution infrastructure and the need of highly trained medical personnel have significantly affected the application of mass immunization programs in developing countries. In addition, recent studies have shown that up to 10% individuals fail to develop a protective immune response to current vaccines and are exposed to infection (3). In the case of HCV, although intensive research is undergoing, no vaccine has been developed yet and 3-4 million of new infections are expected to occur every year.

In this context, affordable vaccines and treatments against these diseases are essential for reducing the loss of life and economic burden to the health sector and individuals in Romania, Europe and rest of the world. With the economic difficulties Europe is facing, reduction of costs in the health sector and saving lives are definitely our responsibilities of European scientists. We propose therefore a Romanian -Norwegian project on: “Developing a cost effective Romania-Norway joint plant-based technology platform for production of oral and intravenous vaccines against Hepatitis viruses HCV and HBV” which aims to (i) develop a cost-effective and safe plant-based production system for HCV and HBV vaccines via tobacco chloroplast genetic engineering and transient expression systems, (ii) determine the functionality of the tobacco chloroplast-derived HCV and HBV vaccines. The cost of downstream processing for plant-made pharmaceuticals and vaccines is usually about 80% of the total production cost. However, edible crops offer unique advantages in significantly reducing these costs. We take thus our experience in tobacco produced vaccine development a key step forward by aiming to (iii) establish an innovative oral vaccine production platform, (iv) produce HCV and HBV vaccines for oral administration, (v) establish the immunogenicity of the experimental HBV and HCV vaccines and (vi) conduct a socio-economic evaluation of the tobacco and edible crop (lettuce) derived HCV and HBV vaccines. Capacity building by recruiting a PhD student in Romania and dissemination of our knowledge and project results are also important for the project and well planned. In addition to Norway and Romania, the project consortium includes also experienced European scientists from leading institutions in Germany and France.

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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