PON01_00117 Antigens and Adjuvants for Vaccines and Immunotherapy

Leader

Novartis Vaccines & Diagnostics Ltd.

Duration

36 months

Keywords

Biotechnology, human health, microalgae

ERC sectors

LS7_3, LS6_11, LS7_9

Summary of the project

The therapeutic benefits of a stimulation of the innate immune system are well documented. Many substances of natural origin, including some lipidic or glycolipidic molecules are able to stimulate various cellular components of the innate immune system. Therefore metabolites of low molecular weight or lipid components of extracts of marine eukaryotic microorganisms may have activating properties of the innate immune cells and act as adjuvants or immune-modulators.
The innovative approach proposed in this project is based on a public-private partnership and belongs mainly to Areas of Convergence (Sicily, Calabria and Campania).
The project aims to achieve three important goals: 1. The development of innovative vaccines for bacterial and viral infections 2. The development of new molecules with adjuvant action and the study of the mechanism of action of those already known 3. The development of more effective and safe new viral vectors for the development of new vaccines.
The role of the Zoological Station in the project is to identify and cultivate species of marine microalgae that show potential antigen and adjuvant activities.

Descriptinos of the activity

The project involves 3 objectives:
OR 1. Identification of antigenic candidates for the development of potential vaccines against Streptococcus pneumoniae, Clostridium difficile, Escherichia coli pathogens, HCMV
OR 2. Identification of new adjuvants and analysis of the mechanism of action of known adjuvants
OR 3. Identification and validation of new Adenovirus and MVA vectors and Virus Like Particles for use as potential vaccines against infectious diseases (HCMV, Malaria, Influenza, RSV, etc.)
 The Zoological Station participates in activity 2.1
Activity 2.1. Identification of novel natural compounds with immune-modulatory and adjuvant activity from marine microalgae
and in particular in:
RI 2.1.1. Preparation of extracts and fractions from microalgae, isolation and identification of substances with immune-regulatory properties (Stazione Zoologica).
Extracts of marine organisms have already been shown to contain immune-regulatory substances (eg alpha galoctoside ceramide that can stimulate NKT cells) and lipids other than those present in humans. This project aims not only to identify new molecules able to interact with the immune system, but also to identify compounds for therapeutic formulations, for example compounds as adjuvants for vaccines. To this end, the group of dr. Ianora is preparing pellets of microalgae for the isolation and identification of substances with potentially immune-regulatory activity. The fractions are assayed by industrial partners (Novartis) for their ability to activate various cells and receptors of the innate immune system. The study will be performed in collaboration with IBB-CNR (SZN sub-contractor) who will characterize the various active components through the use of NMR techniques.

Time chart

Expected results

To obtain at least one new natural compound from marine microalgae with immuno-stimulatory or adjuvant activity.

Tab 1 Costs

Tab 2 Personnel SZN

PON01_02093 Study of new technologies and technological platforms for the improvement of production processes of active pharmaceutical ingredients of industrial interest and search for new bioactive molecules from natural sources

Leader

Sanofi-Aventis S.p.A.

Duration

36 months

Keywords

natural medicines, chemotherapy, microalgae

ERC sectors

LS7_3, LS9_9

Summary of the project

The overall objective of the project is the study and application of advanced and innovative technologies for the  improvement of productive processes of pharmaceutical industry and the search for new molecules with potential pharmacological activity in the anti-infective, anti- cancer and anti-inflammatory field.
The first research line of the project will study the most innovative aspects of technologies of microbiology and genetics of producer strains.
The second research line will study the possibility to identify new products as candidates of potential pharmaceutical interest in the fields of anti-infectives and more generally in cancer and chronic-degenerative diseases connected with ageing, with particular attention to inflammation role. These activities will be focused on the search for new substances of pharmacological interest by screening extracts from microorganisms and / or aquatic organisms and on the characterization of their beneficial and anti-infection properties.
The project will allow the maintenance of a high scientific and technological concentration of great innovative potential characterized by an organic collaboration between industrial and academic researchers.

Description of activities

The project is divided into two lines, each divided into four development objectives (OR) according to the following scheme:
OR 1.1 - Genetic Improvement / genomic technologies
OR 1.2 - Genetic Improvement / Strain improvement
OR 1.3 - Physiology of fermentation
OR 1.4 - Extraction / Purification
OR 2.1 - New methods for the search of bioactive molecules by microorganisms
OR 2.2 - Summary of chemical derivatives of mature products
OR 2.3 - Identification of target and natural compounds relevant to cancer diseases, and chronic degenerative diseases associated with aging
OR 2.4 - Screening and characterization of extracts from marine organisms
The Zoological Station will be involved in the following activities:
OR 2.4 - Screening and characterization of extracts from marine organisms
The purpose of this Objective is the identification of new active principles with antimicrobial and / or antitumor and / or protective activity against neurodegeneration and / or aging. To achieve this goal the Zoological Station will perform the following activities:
ARI 2.4.1 - Identification of bodies from which to extract the active ingredients and their collection
Will be identified already known that microalgae can be a source of active ingredients with antimicrobial activity, antitumor, antineurodegenerativa, anti-aging. The selection will be made on the basis of their environmental activities.
ARI 2.4.2 - Extraction and sample preparation
Each species of microalgae will be cultivated to SZN so as to obtain a sufficient biomass for the extraction of small molecules by the Institute of CNR of Biomolecular Chemistry (ICB-CNR) as a third party custodial .. Once you have identified the active fractions from the other partners will identify molecule chemistry by the ICB and production in the SZN algae that produce these molecules.

Expected Results

Identification of at least one product that has the characteristics to be evaluated as a new "lead candidate" (New Product).

Time charts

Table 1 Costs

Table 2 Personnel SZN

Project financed in the framework of PON R&C 2007-2013 - PAC Enhancement of public research infrastructures

Coordinator Raffaella Casotti

The project concerns the enhancement of research infrastructures for marine environment located in the Convergence Regions Sicily, Campania and Puglia, where the sea is a primary opportunity of development. The project, called EMSO‐MedIT is the Italian contribution to the consolidation in the above mentioned regions of the European research infrastructure EMSO, which, within the context
of EMSO‐MedIT, is in synergy with the other ESFRI coordinated by Italy (KM3NeT and EMBRC) and the Italian initiative for marine research RITMARE.
 
The actions foreseen will be carried out according to the following objectives:

1) enhancement of marine infrastructures and of scientific and technological facilities to strengthenand expand the network for multidisciplinary monitoring of coastal, deep and the water column
marine environment;

2) networking of all existing and enhanced infrastructures for the transmission in real‐time/near‐realtimeintegrating the data from fixed and relocatable observing systems;

3) establishment of a mobile system of intervention to be used for monitoring campaigns at sites ofstrategic interest or in the case of environmental emergencies.

The network of monitoring infrastructures will be further enhanced through the creation of anexchange information system that will enable the sharing of the large amounts of data, providing access to a large community of Italian and foreign users.

Our role: We are partners of the project and in charge of the WP2 "Strengthening of Campania", together with INGV for the Gulf of Pozzuoli. The expansion includes the acquisition of different oceanographic instrumentation, including a WaveGlider, an ROV, and various sensors, but mainly two buoys type elastic beacon to locate in the Gulf of Naples and Gulf of Pozzuoli for the real-time monitoring and data transmission to the control center of physical and biological environmental data.
Partners: National Institute of Geophysics and Volcanology (INGV), Anton Dohrn Zoological Station (SZN), National Institute of Nuclear Physics (INFN), the National Research Center (CNR), National Institute for Environmental Protection and Research (ISPRA)

IRMA: Implementation and Remote Connection for Real Time Moniotoring of Marine Microorganisms

Funded by the Italian Ministry of University and Education (MIUR)
Scientific Coordinator Raffaella Casotti

This project proposes to use a prototype for the automatic, continuous staining of bacteria for the in situ high frequency monitoring (several times a day, up to every 30 min). This instrument will complement the tools already available to SZN for the monitoring of photosynthetic microorganisms, allowing the definition in close temporal and spatial scale of the microbial compartment. We will study the feasibility of use on sampling boats, even without any technical supervision and, in the long term, on buoys. The data produced will provide useful information on the microbial dynamics at very small time scale in several coastal sites. The final product will be a demonstrator of multiparameter monitoring station that transmits environmental data from different sources in real time, operated remotely, helping to build an early warning system for environmental risk

Our role in the project is to coordinate actions and to test, calibrate and validate the prototype

Partners: SZN, CytoBuoy bv (Holland, George Dubelaar), Eawag (Switzerland, Frederick Hammes), CNRS- MIO (France, Gérald Grégori, Melilotus Thyssen, Michel Denis), INGV (Italian, Giovanni Iannaccone, Sergio Guardato)

Financed by the ENPI CBC Mediterranean Sea Basin 2007/2013 Program of the European Union
Scientific Responsible Raffaella Casotti

The project aims to provide the necessary technical and organizational support, especially to small and medium-sized enterprises (existing and potential) that operate in the food sector and in other traditional sectors of tourism, to promote coordinated actions aimed at increasing the share revenue from tourism which benefits the economies of the countries of the Mediterranean. The main result of the project is the creation of new business activities related to sustainable tourism in four coastal areas with significant natural and cultural resources and the strengthening of alliances with companies through the adoption of an approach to public / private management, quality standards and incentive systems that are coupled objectives of economic development with the protection and enhancement of natural / cultural heritage.

In addition, the project will create an international network of sustainable coastal tourism destinations in the Mediterranean Sea basin as a place for the development of common methodologies during project implementation and in the long run such as monitoring and promotional platform owned by local users, national and scientific and open to new subjects, that could spur further development of sustainable coastal tourism on the Mediterranean route.

We are partners in the project and our role is to create the environmental monitoring system of the three sites in order to a) provide real-time data on environmental conditions b) raise awareness among visitors to environmental issues, spreading the sceintific culture through actions such as "citizen science" c) train tourism operators so that they are aware of the environmental value of their sites and participate in their development and conservation

Partners: the Ministry of Cultural Heritage and Activities (coordinator), the Sinis Peninsula (Sardinia), the Zoological Station Anton Dohrm, the city of Mahdia (Tunisia) and the National Institute of Marine Sciences and Technology of Tunisia , the Al-Balqa Applied University and the Marine Protected Area of Aqaba (Jordan)

Summary

The DiaEdit project, Development of genetic tools for the establishment of routine genome editing in the marine diatom Phaeodactylum tricornutum, is part of the initiative “Increasing the Potential of Marine Microeukaryotes as Experimental Model Systems through the Development of Genetic Tools” promoted by the Gordon and Betty Moore Foundation.
The recent development of genetic tools for targeted genome editing of diatoms constitutes a great opportunity for the characterization of molecular processes in these ecologically important algae. Genome editing technologies in diatoms, however, are still in their infancy regarding their routine application. Targeted mutagenesis in diatoms is challenging because of their mostly diploid state and the current lack of efficient homologous recombination.
In this project we propose to enlarge knowledge and tools for genome editing in the molecular model species Phaeodactylum tricornutum, an essential requirement to transfer these technologies to other diatoms. We plan to develop and/or validate three different approaches for genome editing: a TALEN-based approach, the utilization of CRISPR/Cas9 and a viral integrase system.

What we do

SZN is involved in Task 4 "Control of nuclease expression", aimed at the improvement of the specificity of action and expression of the nuclease used to modify the genome. This will be done mainly by identifying promoters that can allow fine control of the nuclease expression. NGS (next generation sequencing) will be used to assess the level of specificity of the chosen system by re-sequencing engineered clones.

Partners

SZN; Universitè Pierre et Marie Curie Paris, France; University of Konstanz, Germany; Norwegian University of Science and Technology, Norway; Tel Aviv University, Israel; Biological Systems and Biochemical Engineering Laboratory INSA/CNRS, France.

Research Area

Functional Genomics, Marine Biotechnology

Project Lifetime

October 2015 - September 2017

SZN Role

Partner

SZN Principal Investigator

Mariella Ferrante

Project Leader

Angela Falciatore, UPMC

Funding Institution

The Marine Microbiology Initiative funded by the Gordon and Betty Moore Foundation (USA).

Dedicated website

Under construction

Personnel involved

Mariella Ferrante, Principal investigator
Monia Russo, Senior Post-doc

Summary

EMBRIC, European Marine Biological Research Infrastructure Cluster to promote the Blue Bioeconomy, is a large project with the overarching objective of building interconnectivity along three dimensions: science, industry, and regional RDI policies. The expected endpoint is the formation of a perennial cluster of research institutes (RIs), which will foster innovation in marine biotechnologies. To prepare this sustainable cluster, EMBRIC focuses on two specific sectors of marine biotechnology, namely (i) discovery and development of marine natural products, and (ii) marker-assisted selection in aquaculture.

SZN is involved in WP7 and WP10.
The objective of WP7 is to demonstrate that linking complementary expertise in biology, analytical chemistry and genetic engineering can provide the blue biotechnology industry with high-performance strains from across the diversity of microalgae. This will involve:
1) Proof of concept that strains from across microalgal diversity constitute a rich resource of natural products for commercial exploitation.
2) Proof of concept that microalgal strains can be genetically engineered to improve their performance capabilities for commercial exploitation.
3) Proof of concept that selective breeding in microalgae in combination with genotype screening can produce strains with improved performance in commercial applications.
The objective of WP10 is to demonstrate that:
1) The external scientific user community is interested in using EMBRIC, i.e., infrastructure workflows across multiple RI-partners.
2) RIs within EMBRIC do provide integrated, interoperable transnational access.
3) Translational access to EMBRIC combined with interdisciplinary collaboration with in-house researchers can initiate Key Enabling Technologies.
4) Translational access aids external users with the maturation of their ideas for Technology Transfer.

What we do

Within WP7, the SZN will contribute to the identification of bioactive compounds from microalgal strains and to the generation of genetically engineered diatom strains.
Within WP10, the SZN will manage the translational access, coordinating the scientific, technical and logistic access to the different RIs involved.

Partners

27 partners from seven European countries plus one Israeli institution are involved in this project.

Research Area

Marine Biotechnology

Project Lifetime

June 2015 – May 2018

SZN Role

Partner

Principal Investigator

Wiebe Kooistra, WP10 and Steering Committee member for SZN
Mariella Ferrante, WP7

Project Leader

Bernard Kloareg, France

Funding Institution

European Commission, under the H2020-INFRADEV-4 call

Dedicated website

www.embric.eu

Personnel involved

Mariella Ferrante, Researcher
Wiebe Kooistra, Senior Researcher
Adrianna Ianora, Senior Researcher
Marina Montresor, Senior Researcher

COCONET - Towards COast to COast NETworks of marine protected areas (from the shore to the high and deep sea), coupled with sea-based wind energy potential

Summary

The Project will identify groups of putatively interconnected MPAs in the Mediterranean and the Black Seas, shifting from local (single MPA) to regional (Networks of MPAs) and basin (network of networks) scales. The identification of physical and biological connections with clear the proceses that govern patterns of biodiversity distribution. This will enhance policies of effective environmental management, also to ascertain if the existing MPAs are sufficient for ecological networking and to suggest how to design further protection schemes based on effective exchanges between protected areas. The coastal focus will be widened to off shore and deep sea habitats, comprising them in MPAs Networks. Socioeconomic studies will integrate to knowledge-based environmental management aiming at both environmental protection (MPAs) and clean energy production(OFW). Current legistations are crucial to provide guidelines to find legal solutions to problems on the use of maritime space. Two pilot project (one in the Mediterranean Sea and one in the Black Sea) will test in the field the assumptions of theoretical appproaches. The Project covers a high number of Countries and involves researchers covering a vast array of subjects, developing a timely holistic approach and integrating the Mediterranean and Black Seas scientific communities through intense collective activities and a strong communication line with stakeholders and the public at large.

SZN role

SZN works as sub-partner of CONISMA and is responsible of assessment of genetic diversity and connectivity within Pilot sites (South Adriatic Sea and Black Sea) in two seagrass species, Posidonia oceanica and Zostera noltei.

Partners

3e, Belgium; Clu, Italy; Cnr-Ismar, Italy; Cnrs, France; Coispa, Italy; Conisma, Italy; Csic, Spain; Dtu Aqua, Denmark; Geoecomar, Romania; Hcmr-Ioo, Greece; Iber-Bas, Bulgaria; Ibmk, Montenegro; Ibss Nasu, Ukraine; Ieo, Spain; Ih Cantabria, Spain; Inat, Tunisia; Io-Bas, Bulgaria; Iolr, Israel; Israbat, Morocco; Istanbul University, Turkey; Metu, Turkey; Mhi, Ukraine; Naturebureau, Uk; Nea, Georgia; Nenuphar, France; Nersc, Norway; Nimrd, Romania; Obibss, Ukraine; Rshu, Russia; Sinop University, Turkey; Sio Ras, Russia; Ukrsces, Ukraine; University Of Malta, Malta; University Of Rostock, Germany; University Of The Aegean, Greece; University Of Zadar, Croatia; Unizkm, Albania; Usof, Bulgaria; Ustv, France.

Project lifetime

2012-2015

P. I.

Gabriele Procaccini
Project coordinator: Ferdinando Boero (University of Salento, Italy)

Funding Institution

EU, FP7-KBBE

Contribution to SZN

€ 47,506.65

Website

http://www.coconet-fp7.eu

ESSEM COST Action ES0906: Seagrass productivity: from genes to ecosystem management

Summary

The main objective of this Action is to provide the scientific basis for estimating and preserving the goods and services arising from the productivity of European seagrass ecosystems under anthropogenic pressure. Seagrass ecosystems rank with coral reefs and tropical rainforests in their many ecosystem services, yet are drastically declining worldwide as a consequence of both anthropogenic and natural pressures including habitat fragmentation, eutrophication, poor water clarity and climate change stressors. In spite of this, the level of awareness is low and management ineffective. Seagrass research is fragmented and there is little integration between researchers and coastal zone managers. The Action aim is to form a European-wide research coordination network that integrates expertise in physiological ecology, ecological genomics and conservation-resource management.

SZN role

G. Procaccini, Management Committee member and coordinator of the WG2. Develop functional genetic and genomic tools to understand seagrass photosynthetic responses to environmental stressors.

Project lifetime

2011-2014

P. I.

Gabriele Procaccini
Project coordinator: Rui Santos (University of Algarve, Portugal)

Funding Institution

EU - ERF

Website

FB: Seagrass Productivity _ Cost Action ES0906

GRASSMET - Climate change effects on seagrass secondary metabolism: ecological implications

Summary

This project aims to answer a relevant but yet unexplored question concerning the implications of climate change on seagrass communities: what will be the impact of changes in the relative availability of carbon and nitrogen in the plant’s primary and secondary metabolite profiles and how will this affect seagrasses capacity to defend themselves against oxidative stress and against epiphytes and herbivores? Seagrasses form some of the world's most productive marine ecosystems, with a very high ecological and economical importance and yet little is known regarding the physiological and ecological consequences of climate change on these plants. Most climate change scenarios predict that atmospheric C_O2 concentrations will reach values in excess of 700 ppm before 2100, changing the relative availabilities of carbon and other nutrients, with foreseen important impacts on plant metabolism. Based on what is known for land plants, it is expected that C assimilation and N use efficiency will increase with rising C_O2 availability, with direct consequences to the C:N balance in plant tissues. In this scenario, it is likely that seagrasses defence capacity be significantly affected, since the molecules involved in defense processes are also rich in carbon and/or nitrogen and share metabolic pathways with carbohydrates and amino acids synthesis. The antioxidant system depends on the activity of several enzymes, phenolic compounds and alkaloids, molecules with distinct compositions. While polyphenols, a large group of phenolic compounds, are N free, alkaloids are N containing compounds. In addition, phenolics, alkaloids and antioxidants, all play important roles in allelopathy and in the plant-epiphytes-herbivores relationships. Therefore, changes in carbon and nitrogen availabilities have the potential to affect not only seagrasses stress responses, but also the settlement of epiphytic communities and the grazing activity. To address this complex question, we designed a stepwise plan, that starts by optimizing the analytical methodologies for the screening and identification of the phenolic compounds, alkaloids, amino acids and soluble sugars in seagrasses, focusing on the molecules known to be relevant to defensive mechanisms, due to their antioxidant, allelopathic or anti-herbivory activity. The second step will be to investigate the effect of high C_O2 and different nitrogen concentrations on the phenolics:alkaloids balance. This will be done through a series of manipulative experiments to be conducted in the mesocosm facility already in place at the CCMAR marine station and also by sampling plants at the vicinity of submarine volcanic vents in the Mediterranean where C. nodosa plants are exposed to naturally high C_O2 and low nitrogen concentrations. Finally, we will investigate how different metabolite profiles will affect plants-epiphytes-herbivores relationships, again using a series of mesocosm manipulative experiments. To acomplish the ambitious worklplan, we assembled a team that largely derives from two previous sucessful projects that have set the stage for this natural followup, the European Science Foundation COST action "Seagrass productivity: From genes to ecosystem management" (ES0906) and the FCT-funded project "High-C_O2 effects on seagrass photosynthetic ecophysiology" (PTDC/MAREST/ 3687/2012). The seagrass Cymodocea nodosa was selected as a model species, for which the team has recently sequenced the full transcriptome, making available a large amount of molecular resources. Methodologically, we shall use an innovative combination of ecophysiological tools, coupled to genetic techniques, in order to link the biochemical processes to the underlying transcriptional responses. Previous work by the team, relating functional genomics with ecophysiology, has revealed new perspectives about how marine angiosperms respond to environmental pressures and have paved the way for this next step.

SZN role

Participant Institution for the genetic characterization of Cymodocea nodosa individuals in situ and in mesocosms experiment and for assessment of gene expression in situ and controlled conditions.

Partners

University of Algarve, Portugal; Stazione Zoologica Anton Dohrn, Italy

Project lifetime

2015-2016

P. I.

Gabriele Procaccini
Project coordinator: Joao Silva (University of Algarve, Portugal)

Funding Institution

Ministerio da Educacao e Ciencia - Portugal