Contract Agreement: 671881 Website: www.pandora-h2020.eu
Coordinator: Consiglio Nazionale delle Ricerche – Istituto di Biochimica delle Proteine – Italy – Dr. Diana Boraschi
Table 1 Consortium List.
No. Beneficiary name Short name Country
1 Consiglio Nazionale delle Ricerche CNR Italy
2 Paris-Lodron Universität Salzburg PLUS Austria
3 Università di Genova UNIGE Italy
4 Academy of Sciences of the Czech Republic IMIC Czech Republic
5 Eberhard-Karls-Universität Tübingen EKUT Germany
6 University of Ljubljana UNILJ Slovenia
7 Cardiff University CU UK
8 Natural Environment Research Council NERC UK
9 AvantiCell Science Ltd. ACS UK
10 Fundaciò Institut Català de Nanociencia i Nanotecnologia ICN2 Spain
Contents
1 Summary ... 83 2 Background ... 84 3 Scientific and technological challenges ... 84 4 Objectives ... 84 5 Organisation ... 85
6 Progress to date ... 85 7 Expected Impact ... 85 8 Directory ... 86 9 Copyright ... 87
1 Summary
Project Duration: 48 months Project Funding: EUR 2,814,491.16
PANDORA (Probing safety of nano-objects by defining immune responses of environmental organisms) shall assess the global impact of engineered nanoparticles (NP) on the immune responses of representative organisms covering all evolutionary stages and hierarchical levels from plants to invertebrates and vertebrates.
Immunity is a major determinant of the survival and fitness of all living organisms, and therefore immunosafety of engineered NP is a key element of environmental nanosafety. PANDORA will tackle the issue of global immunological nanosafety by comparing the impact of widely used NP (e.g., iron, titanium and cerium oxide) on the human immune response with their effects in representative terrestrial and marine organisms. This comparison will focus on the conserved system of innate immunity / stress response / inflammation, aiming to identify common mechanisms and
markers across immune defence evolution shared by plants (Arabidopsis), invertebrate (bivalves, echinoderms, earthworms), and vertebrate (human) species. PANDORA’s objectives are: 1. To identify immunological mechanisms triggered by nano-objects, and predictive markers of risk vs. safety; 2. To do so by a collaborative cross-species comparison, from plants to human, of innate immune defence capacity, using selected, industrially relevant NP; 3. To design predictive in vitro assays to measure the immuno-risk of NP to the environment and human health, as new approaches to industrial and environmental nanosafety testing. PANDORA will train 11 PhD students in an overarching training programme involving training-by-research, joint courses of technical, scientific and transferrable skills, participation to public scientific events, and an intense intersectoral networking exchange plan. The PANDORA consortium encompasses academic institutions, research centres, and SMEs, all with proven experience in higher
education and training, and state-of-the art scientific and technical expertise and infrastructures.
2 Background
PANDORA aims at studying the effects of engineered NP on the immune and defensive responses of environmental organisms and at identifying common mechanisms/markers across species (from plants to humans) that could be used for novel assays for assessing immuno-nanosafety.
The particulate nature of NP dictates a preferential interaction with cells of the immune system deputed to recognition and elimination of foreign particulate matters. It is therefore of key importance that, even for NP that are non-toxic (i.e., unable to kill cells or organisms) according to regulatory approved standard assays, additional evaluation of their interaction with the immune system is performed. PANDORA will focus on the interaction of NP with cells and molecules of the innate immune system. Innate immunity is the rapid and non-specific defence system that reacts to and eliminates foreign materials (infectious microorganisms, dusts and particles) that enter the body. Innate immunity is the only mechanism of immune defence in plants, invertebrates and lower vertebrates, while in higher vertebrates adaptive immunity is also present, adaptive immunity (more specific but much slower).
The full functioning of innate immunity is of central importance for the survival and health of environmental organisms.
Whether NP may induce an anomalous innate reaction or interfere with a protective reaction (e.g., against an infectious agent) is an issue of high relevance for predicting a nanorisk.
3 Scientific and technological challenges
PANDORA aims at identifying the effects of NP on the immune responses of environmental organisms.
The rapid development of nanotechnologies worldwide has fostered intense studies regarding the safety of engineered NP, which enter in an increasingly larger number of consumers’
products and industrial applications and are released into the environment. The effects of NP on human health are actively studied also in relation to the development of nanomedicine. The immunosafety of NP is a major issue for human health, because of the possibility that NP, even if not directly toxic, may alter the functionality of immune cells thereby posing significant health risks.
Environmental nanotoxicology, on the other hand, has dedicated little/no attention to the effects of NP on the immune responses of environmental species. Defensive immune responses are present in practically all living organisms and some of the basic mechanisms are remarkably conserved throughout evolution, in particular those of the so-called “innate” immune system.
Pathogen-sensing receptors such as the human Toll-like receptors (TLR) are practically identical to invertebrate Toll receptors, and to the pathogen receptors found in plant cells. Innate effector molecules (antimicrobial peptides, degrading enzymes, complement) and innate effector cells (phagocytes) are practically identical in most living organisms.
The study of the immune response, integrated with ecological, evolutionary and population biology information, has led to the development of one of the most rapidly expanding fields of biology, Ecological Immunology, which examines the impact of environmental stressors on the immune response and how these stresses maintain the variation in the immune function in the context of evolution and ecology. The importance of defensive mechanisms (that ensure survival but also physical fitness and consequently reproductive capacity) underlines the need of assessing the effects of NP on the immune response of environmental organisms.
4 Objectives
PANDORA aims at training eleven PhD students into the issue of immuno-nanosafety. The focus on the effects of NP on the functionality of the immune system, and consequently on the overall health protection of the target organism, will be broadened from the attention to human health to encompass a variety of environmental organisms (plants, invertebrates, marine, earth).
The programme will therefore lay the basis for an integrated approach to environmental nanosafety that includes immunosafety as a key element. All the selected students will be involved in a highly stimulating training programme, both at the local and at the network-wide level. The training programme comprises:
1. The implementation of the individual research project at the host institution. The research project will involve collaborations with other PANDORA institutions, to be implemented through secondments.
2. Each researcher will be involved in local training sessions.
3. Joint scientific courses and meetings will be organised by the PANDORA consortium, together with short courses for transferable skills training, including a course on ethics.
4. Organisation of a final joint workshop on “Immuno-nanosafety:
innate immune mechanisms in environmental species”.
The research activities implemented in PANDORA have the following objectives:
1. To identify immunological mechanisms triggered by nano-objects, and predictive markers of risk vs. safety;
2. To do so by a collaborative cross-species comparison, from plants to human, of innate immune defence capacity, using selected, industrially relevant NP;
3. To design predictive in vitro assays to measure the immuno-risk of NP to the environment and human health, as new approaches to industrial and environmental nanosafety testing.
PANDORA will address the challenge through the collaborative efforts of eleven partners with different expertise that complement each other towards the overall goals of the project.
One partner (10) will produce the NP, examine their interaction with relevant organic/biological matrices (blood, soil, marine water, etc.), and correlate NP characteristics with effects raised in different species. Four partners (4, 6, 7 and 8) will focus on the toxicology and innate reactivity of different terrestrial invertebrates, two will study the innate immune reactivity of marine organisms (3 and 1.b), and one (5) will address plant immunity. Two projects (1 and 2) will study vertebrate (human) innate immunity, aiming at comparing cells and mechanisms involved in reaction to NP across species, in order to identify common pathways and markers. One project (9) will exploit the consortium expertise and accumulated knowledge for developing predictive assays. Partners will work in strict collaboration, with frequent secondments of the fellows to other partners’ labs.
5 Organisation
The Consortium will act under a strong and well-organised management structure, encompassing three bodies: the Project Coordinator, the External Advisory Board, the Supervisory Board and the Thesis Committees.
6 Progress to date
The overall project kick-off meeting took place at the CNR, Napoli, Italy on January 26th-27th, 2016, where the procuedures for recruitment of fellows and other key consortium-wide issues were agreed. Following the recruitment phase, this was followed by a Fellow’s Kick-Off Meeting on February 22nd – 23rd, 2017 Residència d'Investigadors, Barcelona, Spain. The photos below show the Pandora Fellows and the entire Pandora consortium.
The exposure of the Pandora fellows to different disciplines (from nanotechnology to evolution of immune responses to human immunity to safety/toxicology) and the intense exchange programme will allow them to expand the range of their scientific and technical knowledge and to learn how to work in multidisciplinary collaborations.
Likewise, the industrial interest of the participating SMEs in the field of nanosafety assessment and screening will provide the fellows with a technical capability that is both specialised and marketable and, with their additional experience of working at the interface between academia and industry, should enhance their career prospects in both sectors.
Moreover, the transferable skill courses foreseen in PANDORA will provide the Early Stage Researchers with the necessary tools to become project managers, to find funds and to communicate effectively to different stakeholders or non-scientific media.
The courses will guarantee that all ESRs will receive enough knowledge on various complementary topics to foster their entrepreneurial mind-set. The intersectoriality and interdisciplinary aspects of the partnership will create a generation of scientists able to adapt to changes in global technology and that will represent an investment into the research livelihood of the European Union.
7 Expected Impact
PANDORA presents a good mixture of scientific objectives coupled to technical objectives, with the technological developments being
weighted equally in significance with the research, as each will foster the other during the course of the project. This mixture is considered likely to equip the individual trainees immediately with eminently marketable skill-sets, which should be attractive to a range of potential employers. The exposure of fellows to different disciplines (from nanotechnology to evolution of immune responses to human immunity to safety/toxicology) and the intense exchange programme will allow them to expand the range of their scientific and technical knowledge and to learn how to work in multidisciplinary collaborations.
Regarding the industrial interest, one of the drivers of ACS participation is the attraction the novel cell-based systems of immune detection will have in the field of nanosafety assessment and across multiple sectors of the life science industry.
In the longer-term, the trainees’ career progression is expected to benefit from the deliberate combination of academic / commercial research experience, wherein the existing, close working
relationship between the partners will create a dynamic working environment spanning the public and private sectors.
Another longer-term benefit arising from successful realisation of a truly interactive programme of R&D will be the imbuing of an entrepreneurial spirit amongst project trainees. This will be encouraged by trainees’ secondments to the industrial partners of the consortium and by exposing them to the industrial environment and commercial considerations that shape industrial research.
The proposed research training programme wants to be considered a step towards the establishment of Europe-wide PhD School of Immuno-nanosafety, a scheme PANDORA will start implementing as soon as the project begins, in terms of agreements for multiple or joint doctorates and that, it is hoped, can formally become a wider PhD School on the basis of a successful outcome to this first programme.
8 Directory
Table 1 Directory of people involved in this project.
First Name Last Name Affiliation Address e-mail
Diana Boraschi Consiglio Nazionale delle Ricerche – Institute of Protein Biochemistry - IBP
Via Pietro Castellino, 111
– 80131 – Napoli – Italy d.boraschi@ibp.cnr.it Valeria Matranga Consiglio Nazionale delle Ricerche –
Institute of Biomedicine and Molecular Immunology «A. Monroy» - IBIM
Via Ugo La Malfa, 153 –
90146 – Palermo – Italy valeria.matranga@ibim.cnr.it
Albert Duschl Paris-Lodron Universität Salzburg - Department of Molecular Biology Department of Earth, Environment and Life Sciences
Corso Europa, 26 – 16132 – Genova – Italy
Laura.Canesi@unige.it
Petra Procházková Academy of Sciences of the Czech Republic – Laboratory of Cellular and Molecular Immunology
Videnska 1083 – 14220 – Praha 4 – Czech Republic
kohler@biomed.cas.cz
Birgit Kemmerling Eberhard-Karls-Universität Tübingen – ZMBP Plant Biochemistry
Damjana Drobne University of Ljubljana – Biotechnical faculty - Biology Department
Večna pot, 111 – 1111 – Ljubljana – Slovenia
Damjana.Drobne@bf.uni-lj.si
Peter Kille Cardiff University – Cardiff School of Biosciences
Museum Avenue – CF10 3AT – Cardiff – United Kingdom
Kille@cardiff.ac.uk
Claus Svendsen Natural Environment Research Council – Centre For Ecology and Hydrology – Wallingford
Colin Wilde AvantiCell Science Ltd. Gibbsyard Building –
KA6 5HW – Ayr – United Kingdom
Colin.Wilde@avanticell.com
Victor Puntes Fundaciò Institut Català de Nanociencia i Nanotecnologia – Inorganic Nanoparticles Group
Campus de la UAB – 08193 – Bellaterra - Spain
victor.puntes@icn.cat
9 Copyright
© 2017, CNR (National Research Council), Napoli, Italy, on behalf of the PANDORA consortium.
PANDORA is an ETN project under the European Commission's Horizon 2020 Programme.
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