PRIN PNRR 2022 - DISB - Dipartimento di Scienze Biomolecolari
ENvironmental DRIvers affecting fattening and calcification process of wild and farmed MUSsels in the Adriatic Sea (ENDRIMUS)
Breve descrizione, finalità e risultati attesi: Mussels, belonging to the species Mytilus galloprovincialis Lamark, 1819, represent the most important species for the Italian shellfish production. In EU, Italy is the second largest producer of this species (coming only after Spain), and the first one in the Mediterranean Region. The production comes mostly from aquaculture in lagoons and open-sea and to a smaller extent, from wild populations in the central and northern Adriatic Sea (77% of Italian production). However, in the last few years, both farmed and wild mussels have shown issues in terms of meat reduction and increased shell fragility, which negatively affect their quality, and hence their market value. Since farming technics have not been substantially modified with time, and changes also affect the wild populations, these impacts are inevitably caused by environmental phenomena that have occurred in recent years. Seen as scientific data regarding how these changes impact product quality are lacking, the current information comes solely from producers. In this contest, the ENDRIMUS Project wants to pose attention on this phenomenon happening in the Adriatic Sea, identifying which environmental drivers can mainly affect the growth of mussels in this area. It has been established in literature that river discharges are the main source of nutrients and other inorganic elements, which are at the base of the trophic web in the Adriatic Sea. By employing an interdisciplinary team of experts in marine ecology and biology, environmental and analytical chemistry, and oceanography, ENDRIMUS will evaluate which environmental drivers mainly affect the growth and quality of farmed and wild mussel populations along a latitudinal gradient from North to South of the Italian Adriatic coast. For this purpose, physical and biochemical features, as well as biological variables of the water column will be investigated, along with phytoplankton community abundance and composition, which represent an important source of food for these filter feeding animals. Biological analysis on mussel content and an in-depth study on the shell features at the macro, micro and nanoscale level will be carried out on samples from farmed and wild mussels collected at different sites, to evaluate how this bivalve species is sensitive to variations in environmental conditions. ENDRIMUS points out the importance of considering multiple environmental parameters to investigate bivalve growth and allow for a proper management of bivalve aquaculture. Indeed, given the great socio-economic relevance of Mytilus galloprovincialis along the Italian Adriatic coasts, projects like this one are crucial to guarantee a knowledge-based management of this important resource. The results produced will be disseminated to international, national, and regional stakeholders and the scientific community, in order to provide useful information for future development in mussel farming.
Importo totale UniUrb: € 67.631
Periodo: 30/11/2023 - 29/11/2025
Struttura UniUrb di riferimento: Dipartimento Scienze Biomolecolari (DISB)
Referente UniUrb: Prof.ssa Antonella Penna
Codice progetto: P2022TEFRY
CUP: H53D23007260001
Enhancing Neurovascular Communication with Carbon-engineered Organs-on-a-Chip: Novel Nanotools for Brain Injury Repair (CALINERO)
Breve descrizione, finalità e risultati attesi: Disorders of the Central Nervous System (CNS) are one of the grand health challenges of this century. The impact on everyday life of patients with brain diseases is severe, and the economic burden is approaching 1 trillion € in Europe alone. Therapeutic development, however, remains limited by poor understanding of the brain, including of the neurovascular unit (NVU). The NVU acts as the gatekeeper between blood and brain for metabolites, disease agents, as well as drugs and participates actively in the pathogenesis of many brain disorders including stroke, dementia, epilepsy, Alzheimer’s disease (AD), Parkinson's disease, amyotrophic lateral sclerosis and traumatic brain injuries (TBI). While difficult to distinguish cause and effect, several clinical studies suggest that dysfunction of the NVU is a cause, rather than simply a consequence, of neurodegeneration. However, the precise role of each NV component (the brain microvasculature, the perivasculature and the brain parenchyma) is not yet fully established, since the current methods used to study NVU mechanisms are simply insufficient. Much research has relied on animals or simple cell models that recapitulate neither the cellular ensemble nor the environment of the NVU. Each component of the NVU seems to play a specific and active role, maintaining the dynamic linkages in reciprocal way under physiological and pathological conditions. Thus, restoring NV coupling should be considered as a potential therapeutic target for such pathological conditions. In modern neuroscience, significant progress in developing therapeutic tools is provided by the increasing use of nanomaterials. In the field of nanotechnology, carbon nanotubes (CNTs) and graphene have shown outstanding promise for the improvement of cell function and are thus ideal candidates for repairing or ameliorating NV defects associated with these disorders. With this project, we aim to develop a new generation of nano-engineered tools, combining the innovative Organs-on-a-Chip (OoC) technology, microfluidic cell cultures chips, with the strong potential of Carbon-based materials (CBMs) for restoration impaired neurovascular communication, and to identify and understand the mechanisms by which the NVU is restored. Specifically, we proposed that CBMs enhance cellular properties, such as cellular growth and vesicle release, and as a result, they can regenerate NV communication. To examine this, we will construct a Carbon-engineered OoC-platform comprising the different NV components, distinct but metabolically coupled, to enhance their crosstalk. Then, we will induce a mechanical perturbation in the NVU-model and characterize the mechanisms with which CBMs regenerate the NV coupling. This approach promises significant outcomes towards the development of novel material for NVU restoration and to provide much-needed breakthroughs in the development of therapeutic approaches to treat brain diseases.
Importo totale UniUrb: € 131.341
Periodo: 30/11/2023 - 29/11/2025
Struttura UniUrb di riferimento: Dipartimento Scienze Biomolecolari (DISB)
Referente UniUrb: Prof.ssa Rossana Rauti
Codice progetto: P2022TKL5T
CUP: H53D23009070001
A Multicomponent Solar Energy Conversion System with Extended Spectral Collection and Improved Efficiency (MUSES)
Breve descrizione, finalità e risultati attesi: GENERAL BACKGROUND Social and economic development of modern societies is deeply based on the access to a low-cost, abundant and relentless supply of energy. Currently, > 80% of the world’s primary energy demand is still covered by fossil fuels, with deleterious effects on climate, health and environment. Nowadays there is a pressing need for more environmentally-friendly and renewable energy technologies, able of reducing the dumping of CO2 in the atmosphere. Solar energy, which is clean, non-hazardous and largely enough to cover the demand of human civilization, satisfies the key requirements for a definitive solution of the energy conundrum [1]. The ubiquitous and large distribution of sunshine in the Mediterranean region, the possibility to generate electricity in-situ by small off-grid production plants, the limited environmental impact with no CO2 generation in the production phase, make solar energy the best solution for sustainable electricity production, particularly at a community level. In this scenario, the conversion of clean and plentiful solar radiation into electricity plays a key role as one of the technologies that are replacing fossil fuels in the generation of mass energy [2].
PROJECT OBJECTIVES Here we propose a viable solution for solar energy collection and exploitation into a smart device with enhanced conversion efficiency and long-term stability. In the development of this new technology particular attention will be devoted to the use of easily available and low-cost materials, characterized by simple and low energy demanding manufacturing methods, facile operability, easy maintenance, and long-term operation. The primary objective of the project is the development of a modular device for solar energy conversion based on two wavelength shifting elements (a down- and an up-converter) coupled to a 3rd generation Perovskite-based solar cell with enhanced photon-to-current conversion efficiency. This design is aimed at recovering the unexploited high- and low-energy part of the solar spectrum, thus increasing the overall conversion efficiency. Particular attention will be devoted to the use of energy-efficient and renewable materials primarily based on Earth-abundant, low-cost and non-toxic elements, synthesized using environment friendly procedures, and exhibiting enhanced device performance with respect to the state-of-the-art.
Importo totale UniUrb: € 77.999
Periodo: 30/11/2023 - 29/11/2025
Struttura UniUrb di riferimento: Dipartimento Scienze Biomolecolari (DISB)
Referente UniUrb: Prof. Gianfranco Favi
Codice progetto: P2022ACY8P
CUP: H53D23007770001
Dual acting rEdox-modulating thiol molecules targeting Viral rEplication and infLammatory respOnse in resPiratory virus infections (DEVELOP)
Breve descrizione, finalità e risultati attesi: The induction of oxidative stress is a common feature among different respiratory virus infections, promoting viral replication and inducing inflammatory response. Although the modulation of some intracellular redox pathways has been reported, the characterization of the antioxidant response, the activation of the Unfolded Protein Response in the redox-sensitive endoplasmic reticulum compartment, as well as the whole proteomic changes associated with virus-induced redox imbalance, remain to be clarified. To this aim, in the present project, redox-modulating thiol molecules will be used to:
a) evaluate their potential antiviral activity, by interfering with different steps of respiratory virus infections, and their anti-inflammatory properties;
b) characterize at the biochemical and molecular level the pathogenetic events underlying respiratory virus infections and their modulation by changes in the intracellular redox status.
The project goals will be achieved by two Research Units (RU) belonging to Sapienza University of Rome (UNISAP), as Principal Investigator, and University of Urbino (UNIURB), which have been collaborating from many years to discover new redox-modulating compounds against viral infections and to understand the complex network of host-virus interactions. The two research groups have long experience in different areas, i.e. microbiology, virology, organic chemistry, biochemistry, molecular and cellular biology, with complementary skills on viral infection, redox modulation and redox signaling as well as on the design and synthesis of (bio)molecules with redox-active sulfhydryl function(s). The research units will share cellular models, instruments, technologies and results to achieve the objectives of the proposal. Our results will provide new knowledge on the mechanisms underlying coronavirus and influenza virus pathogenesis, identifying new cell-targeted therapeutic approaches based on thiol compounds able to counteract oxidative stress and to regulate antioxidant pathways. This approach may have a beneficial effect at the early stage of viral infection or by impairing viral replication and virus-induced lung injury when the infection has already been established.
Importo totale UniUrb: € 118.029
Periodo: 30/11/2023 - 29/11/2025
Struttura UniUrb di riferimento: Dipartimento Scienze Biomolecolari (DISB)
Referente UniUrb: Prof.ssa Alessandra Fraternale
Codice progetto: P2022WRRNT
CUP: H53D23007530001
Development of essential oil-based smart formulates by means of plasma processing: effect against pests and impact on soil beneficial communities (PLASMA4SOIL)
Breve descrizione, finalità e risultati attesi: To drive human activities towards more sustainable production systems, the European guidelines indicate, among others, a more efficient use of the resources and a reduction of the input of synthetic agrochemicals, that are responsible for environmental pollution, alteration of soil system functioning and changes in pest pests population. Hence, there is an urgent necessity to develop new crop pest and pathogen control systems with a reduced impact onto soil health status. Any innovative approach for developing biocidal formulates, based onto exploitation of natural compounds, must be also validated in terms of effects onto the beneficial communities, positively affecting crop tolerance to biotic and abiotic stresses, and increasing soil health and biological fertility. In this scenario, the PLASMA4SOIL consortium proposes to address a huge investigation effort based onto 2 main ideas:
a) Essential oils (EOs) produced by aromatic and medicinal plants are known for a strong activity on crop pests and soilborne phytopathogens, therefore they can be a valid alternative to synthetic biocidal agrochemicals;
b) Plasma processing of materials is a mature environmentally friendly technology that can be effectively used to produce biocidal formulates consisting in granules coated with EOs containing films.
PLASMA4SOIL joins 3 Research Units, CNR, UNIPI and UNIURB, with complementary expertise ranging from materials plasma processing to phytoparasitic and pest species control and microbiota investigation, to propose the development of innovative EOs delivering systems for pests control. More in detail, the project will be organized in 3 main steps:
i) Screening of EOs in terms of their suppressive activity onto phytoparasitic nematodes and insect pests
ii) plasma deposition of EOs-containing nanocomposite coating onto granular supports
iii) evaluation of the biocidal activity of the plasma-prepared formulates and of their impact onto the edaphic microfauna and microbiota.
Such approach represents a breakthrough in the application of EOs in agriculture, since large volume production of suitable formulates containing these natural compounds is still missing and the knowledge on the effect of essential oils onto soil beneficial biotic components is weak. Furthermore, the use of plasma technology to develop natural biocidal agent delivering systems is still an unexplored field.
Importo totale UniUrb: € 52.500
Periodo: 30/11/2023 - 29/11/2025
Struttura UniUrb di riferimento: Dipartimento Scienze Biomolecolari (DISB)
Referente UniUrb: Prof.ssa Federica Semprucci
Codice progetto: P2022MK3AF
CUP: H53D23010630001
Investigation of the role of humoral immunity induced by glycoconjugate vaccines in the control of invasive non-typhoidal Salmonella infections
Importo totale UniUrb: € 88.397
Periodo: 30/11/2023 - 29/11/2025
Struttura UniUrb di riferimento: Dipartimento Scienze Biomolecolari (DISB)
Referente UniUrb: Prof. Giuseppe Stefanetti
Codice progetto: P2022PJYXR
CUP: H53D23007490001
RNA-based therapy by RBCEVs for the treatment of Guanidinoacetate methyltransferase deficiency
Breve descrizione, finalità e risultati attesi: Guanidinoacetate methyltransferase (GAMT; EC:2.1.1.2) deficiency (OMIM: 612736) was recognized as the first autosomal recessive inborn error of creatine (Cr) metabolism in 1994 and is the most severe condition among the cerebral creatine deficiency syndromes (CCDSs). GAMT deficiency is a rare disease (www.orpha.net) with unsatisfactory therapeutic options. At the biochemical level, the disease is characterized by extremely low levels of Cr in the tissues and bodily fluids and by the accumulation of its precursor guanidinoacetic acid (GAA), a highly toxic molecule for the organism, especially for the brain. An attractive and suitable therapeutic option consists of removing the high levels of circulating GAA from blood and restoring normal levels of Cr in the brain throughout the administration of synthetic GAMT, the defective enzyme, in a cellular context capable of providing S-adenosyl methionine (SAM) as methyl donor. We have previously designed a recombinant mutant GAMT enzyme, where only four critical residues were replaced, showing a high stability and solubility as a lead candidate. In cells with limited SAM supply, the entire metabolic pathway also included a recombinant form of human methionine adenosyl transferase (MAT). As a proof-of-concept RBCs co-entrapped with both GAMT and MAT enzymes performed, in vitro, as a competent cellular bioreactor to remove GAA and produce Cr. Furthermore, others and we have shown that extracellular vesicles derived from Red Blood Cells (RBCEVs) are safe RNA drug delivery vehicle that can target liver cells (the main compartment for Cr synthesis). RBCEVs will be produced by a pre-loading method (RBCs loaded ex vivo with modified GAMT mRNA) followed by EVs extrusion and purification (unpublished). RBCEVs loaded with modified GAMT mRNA, will be evaluated in vivo in a validated murine model of GAMT deficiency (already available within the research teams), to test the safety and efficacy of the proposed RNA-based therapy in GAMT-deficient mice. The research teams possess the necessary skills to perform both the biochemical and behavioral studies including metabolomic analyses by UHPLC-ESI-MS/MS mass spectrometry and in vivo magnetic resonance spectroscopy (MRS) detection of phosphorylated Cr and GAA in brain and muscle. In addition, we will evaluate several uncharted behavioral domains: communication, cognition, and sociability of controls and treated mice. In details, we will evaluate sensorimotor reflexes, complex abilities such as sensory and motor skills, odors recognition and preference for social inputs, motor skills development, the sociability domain, Barnes Maze Test, and others as appropriate. The evidence collected during these studies will represent a solid base to test an innovative RNA-based approach in rare diseases caused by enzymatic deficiencies exploiting RBCEVs as a safe gene delivery system applicable to other conditions with high medical need.
Importo totale UniUrb: € 128.000
Periodo: 30/11/2023 - 29/11/2025
Struttura UniUrb di riferimento: Dipartimento Scienze Biomolecolari (DISB)
Referente UniUrb: Prof.ssa Biagiotti Sara
Codice progetto: P202284WZH
CUP: H53D23011070001
De novo L-cysteine biosynthesis in Pseudomonas aeruginosa: pathway assessment for novel antibiotic discovery (ENHANCE)
Breve descrizione, finalità e risultati attesi: Antimicrobial resistance (AMR) is among the most threatening challenges for human health. According to the WHO, AMR is responsible for more than 700,000 annual deaths, a scenario expected to rapidly worsen in the next decades. Pseudomonas aeruginosa is an opportunistic pathogen frequently involved in multi-drug-resistant (MDR), healthcare-associated infections, for which the development of novel antibacterial treatments, possibly exploiting new targets, is most urgent.
L-cysteine (L-Cys) is the precursor of many sulfur-containing biomolecules in bacteria, including reducing agents, cofactors and membrane components, and a main actor in the control of the cell redox state. As such, L-Cys plays an essential role in microbial survival and pathogenicity. The main pathway leading to its biosynthesis through inorganic sulfur assimilation, the reductive sulfate assimilation pathway or de novo cysteine biosynthesis (DeNoCB), is a promising target for the development of new anti-bacterials and/or adjuvants. The DeNoCB, absent in humans, has been extensively investigated in plants, Mycobacteria and several gram-negative bacteria, and many enzymes of the pathway have been structurally and functionally characterized and exploited in medicinal chemistry campaigns. Surprisingly enough, for P. aeruginosa, one of the most threatening pathogens in the AMR era, the DeNoCB still represents a scarcely investigated and totally unexploited pathway for antibiotic discovery. The project aims to fill this gap, by investigating P. aeruginosa DeNoCB through an integrated approach that will exploit the complementary expertise of the two proponent units in the biochemical characterization and inhibition of L-Cys biosynthesis enzymes, and in the physiology, genetics, gene regulation and antibiotic resistance of P. aeruginosa.
The experimental plan includes the preparation of P. aeruginosa deletion mutants in genes encoding key enzymes involved in DeNoCB, their phenotypical characterization (including antibiotic susceptibility and oxidative stress assays), and the recombinant production and functional characterization of the corresponding enzymes. Target enzymes will be selected and used for screening a commercial library. The best hits will be assayed on P. aeruginosa strains, including clinical isolates, for their ability to specifically inhibit L-Cys biosynthesis and bacterial growth (both on planktonic and biofilm-associated cells).
The output of the project will be a detailed description of DeNoCB in P. aeruginosa, the validation of the most promising targets in the pathway, and the preliminary analysis of the effects of small molecule inhibitors on enzyme activity in vitro and on P. aeruginosa. We are confident that this project will significantly contribute to the development and validation of new antimicrobial molecules that could expand the arsenal of available drugs against MDR bacterial pathogens.
Importo totale UniUrb: € 98.172
Periodo: 30/11/2023 - 29/11/2025
Struttura UniUrb di riferimento: Dipartimento Scienze Biomolecolari (DISB)
Referente UniUrb: Prof.ssa Emanuela Frangipani
Codice progetto: P20225HFSK
CUP: H53D23011040001
Sito web: https://enhance.unipr.it/
