BrainMap

Mr. Razvan Stefan Boiangiu

PhD

Teaching Assistant - UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Researcher

Web of Science ResearcherID: not public

Expertise & keywords

Antiaggregation potential of 6-hydroxy-L-nicotine from Paenarthrobacter nicotinovorans pAO1 against amyloid peptide: in vitro and in vivo studies Call name: P 4 - Proiecte de cercetare exploratorie - PCE-2021
PN-III-P4-PCE-2021-1692 2022 - 2024

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

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

Affiliation:

Project website: http://cercetare.bio.uaic.ro/grupuri/bioactive/content/grants/PCE2022_hl.html

Abstract:

Alzheimer's disease (AD) is characterized by progressive degradation of memory processes, being associated with three major changes that occur in the brain: i) the formation of intra- and extracellular beta-amyloid deposits; ii) the appearance of neurofibrillary tangles and iii) the death of cholinergic neurons and a significant decrease in acetylcholine level. The identification of neuroprotective therapies for AD was dominated by the hypothesis of amyloid cascade and tau proteins. Unfortunately, both approaches have so far failed to provide an effective therapeutic strategy. The involvement of α7 and α4β2 subtypes of nicotinic receptors (nAChRs) in the pathogenesis of AD has led to the proposal of a new therapeutic approach. Immunohistochemical studies in the brains of patients with sporadic AD have shown that Aβ1-42 and α7nAChR are present in neuritic plaques and this interaction may be inhibited by α7nAChRs ligands. Nicotine, through its ability to bind to nAChRs is the ideal molecule for the development of new derivatives with therapeutic applications. The project aims to test the antiaggregating potential against Aβ1-42 of 6-hydroxy-L-nicotine (6HLN), derived from the metabolism of nicotine in the microorganism Paenarthrobacter nicotinovorans pAO1. To achieve this goal, the project activities will focus on evaluating the action of 6HLN in vitro on cell lines and in vivo on 5xFAD transgenic mice, in order to identify its therapeutic potential.

Sequencing the genome of a useful bacteria: Paenarthrobacter nicotinovorans – next step in extending it’s biotechnological applications Call name: P 4 - Proiecte de Cercetare Exploratorie, 2020
PN-III-P4-ID-PCE-2020-0656 2021 - 2023

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

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

Affiliation:

Project website: http://cercetare.bio.uaic.ro/grupuri/bioactive/content/grants/PCE2021.html

Abstract:

Paenarthrobacter nicotinovorans pAO1 is a nicotine degrading microorganism that shows promising applications in converting nicotine-containing waste into useful green chemicals. Its biotechnological applications are nevertheless hampered by the lack of knowledge and tools to perform genetic and metabolic engineering. After solving the nicotine-induced proteome of this bacteria, the project leader of the current proposal concluded that none of the draft genomes available for this strain are complete. The current application aims to provide the first complete and annotated genome of P. nicotinovorans pAO1, and, as such, the first complete genome of a nicotine degrading microorganism. In order to achieve this, P. nicotinovorans pAO1 gDNA will be isolated and whole-genome sequencing (WGS) will be performed using two platforms: NGS Illumina for reading depth and ONT MinION for scaffolding and assembling the genome. The quality of the assembly and annotation will be addressed using dRNA-seq and the already available raw proteomics data. The project will not only strengthen the much need bioinformatics know-how in the already existing team of the project leader, but also will group allow the group to generate a genome-scale metabolic model of the nicotine metabolism, and, consecutively, to develop high yield biotechnologies for production on nicotine derivatives.

Steps towards an Arthrobacter nicotinovorans biotechnology for neuro-pharmaceuticals production Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2016-0367 2019 - 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: http://www.bio.uaic.ro/cercetare/grupuri/bioactive/content/grants/te2019.html

Abstract:

6-hidroxy-nicotine (6HNic), a naturally occurring metabolite of Arthrobacter nicotinovorans was shown to bind the nicotinic acetylcholine receptors and to modulate their function. Experimental tests using laboratory rats have demonstrated the ability of 6HNic to cope with the acetylcholine depletion and to restore normal brain functions. 6HNic has been thereby identified as a high impact bio-pharmaceutical with application in the therapy of neurodegenerative disorders associated with low acetylcholine levels.

6HNic is produced in our group by using a genetically engineered strain of Arthrobacter nicotinovorans. The cultivation conditions currently employed allow for a yield of approx. 50 mg 6HNic / 100 ml culture. This is enough for common in-vitro and in-vivo lab test, but not near sufficient for the large scale test required for establishing the real therapeutic potential of 6HNic. The scope of the funding application is to develop a technology for high-yield production of the neuroprotective agent 6HNic using high-density cultures in a bio-fermenter. For this, a genetically engineered Arthrobacter strain will be created by knocking-out specific genes using suicidal vectors. The mutant strain will be further accommodated to a bio-reactor and the conditions for optimum 6HNic production will be evaluated. The final goal is to formulate an high-yield Arthrobacter based method for the production of 6HNic which would allow our group to further deepen the study of nicotine derivatives applications in biotechnology.

Steps towards an Arthrobacter nicotinovorans biotechnology for neuro-pharmaceuticals production Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2016-0177 2017 - 2018

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://www.bio.uaic.ro/cercetare/grupuri/bioactive/content/grants/ped2017.html

Abstract:

6-hidroxy-nicotine (6HNic), a naturally occurring metabolite of Arthrobacter nicotinovorans was shown to bind the nicotinic acetylcholine receptors and to modulate their function. Experimental tests using laboratory rats have shown the ability of 6HNic to cope with the acetylcholine depletion and to restore normal brain functions. 6HNic has been thereby identified as a high impact bio-pharmaceutical with application in the therapy of neurodegenerative disorders associated with low acetylcholine levels. The scope of the funding application is to develop a technology for the production of the neuroprotective agent 6HNic in an industrial-like environment and to test it at a pilot scale. For this, a genetically engineered Arthrobacter strain will be created by knocking-out specific genes using suicidal vectors. The mutant strain will be further accommodated to a bio-reactor and the conditions for optimum 6HNic production will be evaluated. The final goal is to formulate a microbial based biotechnology for the production of 6HNic ready to be transferred to the industrial environment.

Nicotine - from toxic residue to metabolic derivatives with neuroprotective effects Call name:
PN-II 50BM/2016 2016 - 2017

Role in this project: Key expert

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://www.bio.uaic.ro/cercetare/grupuri/bioactive/content/grants/ro-ch2016.html

Abstract:

Both teams from Romania and P.R. China have the same main research interest: the nicotine catabolic pathway in bacteria. The research group from P.R. China coordinated by Tang H., PhD, have cloned, expressed, sequenced and characterized the enzymes nicotine oxidoreductase and 6-hydroxy-3-succinoylpyridine hydroxylase from Pseudomonas putida S16 and managed to show their implication in the transformation of nicotine to 2,5-dihydroxy-pyridine (DHP). The team from Romania, part of the a research group on ''Identification And Characterization Of Biological Active Molecules'' have identified the final degradation steps of nicotine metabolism in Arthrobacter nicotinovoras pAO1 and studied the effect the metabolic intermediate 6-hidroxy-nicotine on the learning and memory processes in rats. Both teams have knowledge, methods, plasmids and recombinant strains which allows the isolation of metabolic intermediates produced by the two bacteria: P. putida and A. nicotinovorans. As the objective of the project is to identify nicotine derivatives with neuroprotective effects, the combined scientific experience of the two teams will increase the repertoire of available nicotine derivatives for experimental testings. Beside the role in suppling the nicotine derivatives, each partner has at least one unique, complementary task. The group in Romania will be responsible for testing the selected nicotine derivatives on laboratory rats in order to identify their effects of memory and learning processes. The group from China is responsible of using genetic engineering techniques (gene-knockout, site-directed mutagenesis) for strain improvement in order to obtain the best yield for transformation of nicotine in valuable compounds. None of these complementary tasks can be fulfilled alone by the other partner.

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