Description of each fellowship:  

Universities involved (Joint Doctorate diploma): POLITECHNIKA WROCLAWSKA (Wroclaw, Poland) UNIVERSITE de LIMOGES (Limoges, France) Employer: POLITECHNIKA WROCLAWSKA (Wroclaw, Poland)

Research project description and main objectives:

One main issue of the POLYTHEA project is to develop photosensitizing dyes which can be used in a modular fashion for a variety of biomedical applications within the consortium. There are multiple advantages in using NIR light for activating photophysical processes relevant for photodynamic therapies. Thus, one of the crucial issues to be solved is optimizing the efficiency of the sensitizers for absorbing photons through nonlinear optical processes while assuring high quantum yields of formation of reactive oxygen species (ROS) that provide the therapeutic action. This project will focus on the design and systematic evaluation of the nonlinear optical properties of tetrapyrrole-based photosensitizers (PS). In particular, the relevant multiphoton cross sections will be determined over wide ranges of wavelengths to provide the peak values at the optimized wavelengths for the photodynamic treatment as well as the appropriate «merit factor». The main objective of this project is providing the necessary support for the development of novel chromophores and biologically relevant nanosystems with optimized nonlinear optical and photophysical properties. Thus, the project is divided into two parts: 1)      Synthesis of PS with enhanced multiphoton absorption properties. 2)      Determination of values of the nonlinear cross section, together with the other pertinent parameters such as quantum yield of ROS production, quantum yield of luminescence and efficiency of photodecomposition Thus the data obtained will provide the feedback to the synthetic work. In vitro biological studies will be also conducted and samples will be investigated using nonlinear microscopy.

Required competencies: The candidate should fulfill all requirement listed in the general offer. Formation and experience in organic synthesis and organic compounds characterization. In particular, experience in conjugated systems and/or tetrapyrrolic chemistry will be a great asset. Formation and experience in nonlinear optical process and photophysical study in general.

Starting date: September 1st 2018 Duration: 36 months Names of supervisors: Dr. Katarzyna MATCZYSZYN (POLITECHNIKA WROCLAWSKA) Dr. Stéphanie LEROY-LHEZ (UNIVERSITE de LIMOGES) Job offer ESR 1

Universities involved (Joint Doctorate diploma): TRINITY COLLEGE OF DUBLIN, THE UNIVERSITY OF DUBLIN (Ireland) UNIVERSITY OF AMSTERDAM (Netherlands) Employer: TRINITY COLLEGE OF DUBLIN (Ireland)

Research project description and main objectives: One ultimate aim of the POLYTHEA project is to develop photosensitizing dyes that can be used in a modular fashion for a variety of biomedical applications within the consortium. This requires an understanding of the fundamental relationship between macrocycle structures, conformation and substitution pattern on the photochemical properties. This project will focus on the design and synthesis of porphyrin-based photosensitizers (PS) with optimized photophysical properties and chemical functionalities suitable for introduction of biological targeting groups and/or for binding to polymeric (nano) carrier materials.

Generally applicable synthetic strategies for unsymmetrically substituted porphyrins, which carry functional groups suitable for subsequent modification will be developed. ABCD-, A2BC- and A2B2-type porphyrins, i.e. porphyrins with meso positions) will be targeted. Depending on the functional groups introduced a modulation of the macrocycle photophysical properties will be achieved through electronic, π-extension, π-modification, and conformational effects on the ring system. They will allow for charge-transfer character (red-shifting the absorption) while a high triplet yield has to be maintained (e.g., by charge recombination to the triplet state). The compounds will be investigated in an interdisciplinary fashion for their spectroscopic and photophysical properties and with regard to their biological up-take.

Required competencies: The candidate should fulfill all requirement listed in the general offer. He/She must have studied chemistry or allied fields, show interest and knowledge in synthesis and/or optical spectroscopy related to molecular imaging.

Starting date: September, 1st 2018 Duration: 36 months Names of supervisors Prof. Dr. Mathias SENGE, Trinity College of Dublin Dr. René WILLIAMS, University of Amsterdam Job offer ESR 2

Universities involved (Joint Doctorate diploma): University of Amsterdam (Amsterdam, The Netherlands) Université de Limoges (Limoges, France) Employer: University of Amsterdam (Amsterdam, The Netherlands)

Research project description and main objectives: One main issue of the POLYTHEA project is to develop photosensitizing dyes which can be used in a modular fashion for a variety of biomedical applications within the consortium. There are multiple advantages in using NIR light for activating photophysical processes relevant for photodynamic therapies.

Thus, this project will focus on the development of new systems than can be excited by NIR light, using for example organic up-converters or triplet formation by charge recombination, in order to produce reactive oxygen species.

This project is divided into two parts:

1)      Synthesis of PS with targeted photophysical properties.

2)      Evaluation of these properties

Required competencies: The candidate should fulfill all requirement listed in the general offer. Formation and experience in organic synthesis and organic compounds characterization.Formation and experience in photophysical studies.

Starting date: September 1st 2018 Duration: 48 months Names of supervisors Dr. René Williams (University of Amsterdam) Dr. Stéphanie Leroy-Lhez (UNIVERSITE de LIMOGES) Job Offer ESR 3

Universities involved (Joint Doctorate diploma): University of Wroclaw (Wroclaw, Poland) University of Neuchatel (Neuchatel, Switzerland) Employer: BET Solutions (Athens, Greece)

Research project description and main objectives: At the forefront of chemistry, nano-materials and biology, this project intends to use cellulose nanocrystals to transport and deliver photo-responsive molecules to biological targets. Four main objectives are foreseen: a) to prepare and characterize cellulose nanocrystals as well as b) photo-responsive molecules; c) to load the nanocrystals with the photo-responsive compounds, and; d) to evaluate the biological potential of the newly developed nano-carriers in in vitro and in vivo models. To achieve these goals, the candidate will have to use synthetic organic strategies to functionalize the photo-responsive molecules in view of grafting them to the nanocrystals, and to learn radio-labelling techniques to optimize visualization and to identify biological targets. Being a multidisciplinary project, the candidate will need to be able to work independently, to possess excellent collaborative skills, and to adapt rapidly to different scientific environments.

Required competencies: The candidate should fulfill all requirement listed in the general offer. Formation and experience in organic synthesis and organic compounds characterization, purification and isolation. Formation and experience in or real interest for radiopharmaceutical chemistry

Starting date: September 1st 2018 Duration: 36 months Names of supervisors Pr. George Loudos (BET Solutions) Pr. Bruno Therrien (University of Neuchatel) Dr. Katarzyna Matczyszyn (University of Wroclaw) Job offer ESR 4

Universities involved (Joint Doctorate diploma): UNIVERSITE de LIMOGES (Limoges, France) TRINITY COLLEGE OF DUBLIN, THE UNIVERSITY OF DUBLIN (Dublin, Ireland) Employer: UNIVERSITE de LIMOGES (Limoges, France)

Research project description and main objectives: One main issue of the POLYTHEA project is to develop photosensitizing dyes and their formulations which can be used in a modular fashion for a variety of biomedical applications particularly for antimicrobial applications within the consortium.

This project will focus on the design, synthesis of photosensitizers (PS) and their different  formulations (with polymers, biopolymers,…) for antimicrobial applications. The best polymers/PS pair will be selected on the basis of photodynamic properties, biocompatibility and stability of bactericidal material, PS repartition in the formulation and in vitro bactericidal effect on planktonic bacteria cells or on bacterial biofilm.

The main objective of this project is providing new formulations of PS, which will allow practical application in various fields such as food safety, self-sterilizing surface, medical materials. Moreover, this study will afford further insight into the photodynamic process of bacteria killing.

Thus, the project is divided into three parts:

1)      Design, synthesis and characterizations of PS for photodynamic therapy antimicrobial applications 2)      Formulation and characterization of these PS/polymers complexes. 3)      Microbiological evaluation of these formulations against planktonic bacterial cells and bacterial biofilm.

Required competencies: The candidate should fulfill all requirements listed in the general offer. Formation and experience in organic synthesis, organic compounds characterization or/and Bio-organic chemistry/Biochemistry. Knowledge in microbiology (basic) will be one more. Ability to work in a cross-disciplinary environment in connection with biologists, chemists and industrials is required.

Starting date: September 1st 2018 Duration: 36 months Names of supervisors Pr Vincent Sol (UNIVERSITE of LIMOGES) Prof. Dr. Mathias Senge (TRINITY COLLEGE OF DUBLIN) Job offer ESR 5

Universities involved (Double Doctorate diploma): Trinity College of Dublin, The University of Dublin (Ireland) University of Coimbra (Portugal) Employer: Trinity College of Dublin (Ireland)

Research project description and main objectives:  A main topic of POLYTHEA is the development of photosensitizing dyes which are highly specific for and photoactive in the target tissue and can be used for the preparation of formulations, nanomaterials and therapeutic applications.

Thus, this project targets the design and synthesis of tetrapyrrolic bioconjugates for use in photodynamic therapy. The bioconjugate groups will be chosen with regard to tissue uptake and intracellular localization, suitability of linker chemistry and to provide additional therapeutic effects.

For that purpose, unsymmetrically substituted macrocycles will be used and chemically linked with suitable targeting and effector units. This will require the synthesis of amphiphilic macrocycles (for improved membrane passage), that act as light-activated medical agents or imaging devices and have additional effector functions (receptor binding, apoptosis induction, oxygen sensing or delivery, tumor indication, radiotherapy), and have tailor-made photophysical and localization properties. Chemical methods will be developed to link long-chain aliphatics, anti-inflammatory compounds, carbohydrates, anti-angiogenic, and others, to the porphyrin macrocycle. A new class of PS will be based on the use of organic scaffolds, which will be modified in such a way as to carry PS, targeting groups and biological effector groups within one delivery system.

This project has platform character and results thereof can be applied to other research areas which require the elaboration of dye molecules in a spatially and functionally defined manner. Thus, it will interconnect chemistry with the spectroscopic and biological aspect of photodynamic therapy field.

Required competencies: The candidate should fulfill all requirement listed in the general offer. She/he must have studied chemistry, biochemistry, biology or equivalent. Experience in synthesis and/or cell biological methods is desirable.

Starting date: September 1st 2018 Duration: 36 months Names of supervisors Prof. Dr. Mathias SENGE (Trinity College of Dublin) Dr. Ligia Silva (University of Coimbra) Job offer ESR 6

Universities involved (Double Doctorate diploma): University of LIMOGES (Limoges, France) University of COIMBRA (Coimbra, Portugal) Employer: University of LIMOGES (Limoges, France)

Research project description and main objectives: The struggle against microbial infections, contaminations is a global issue with important societal impacts, especially with the continuous emergence of antibiotic-resistant bacteria. The development of new bactericidal materials to prevent bacterial colonization of surfaces in various environments (agro-food, medical…) represents a major challenge. In this respect, photodynamic antimicrobial chemotherapy (PACT) is a promising alternative approach to fight bacterial biofilm contaminations. In order to prevent the growth of planktonic bacteria and the formation of biofilms through PACT, it appears to be essential to investigate formulation/coating nature (films, powder, spray, encapsulation …), effect on the photosensitizer (PS) and efficiency in the photodynamic process.

This project will focus on the development of bio-inspired materials with suitable properties to be used as photodynamic drug formulations (light transparency, non-toxicity, stability …) and easy to process. Different approaches will be developed: coating surfaces with biocompatible polymers bearing a photosensitizer (cationic phthalocyanines and porphyrins) trapped inside or grafted.

The main objectives of this project are: (i) the development of new materials, (ii) chemical modification of the photosensitizers and (iii) evaluation of antibacterial properties on both planktonic bacteria and biofilms.

Required competencies: The candidate should fulfill all requirement listed in the general offer. Qualification and experience in organic synthesis and organic compounds characterization, purification and isolation. Qualification  and experience or real interest in cell biology and/or microbiology

Starting date: September 1st 2018 Duration: 36 months Names of supervisors Dr. Stéphanie Leroy-Lhez (University of LIMOGES, France) Pr. M. Mariette Pereira (University of COIMBRA, Portugal) Job offer ESR 7

Universities involved (Double Doctorate diploma): University of Coimbra (Portugal) Trinity College of Dublin (Ireland) Employer: University of Coimbra (Portugal)

Research project description and main objectives: A key aspect of the POLYTHEA project is to develop new tetrapyrrolic photosensitizers (PS) and study them in order to identify quantitative structure–activity relationship (QSAR) for various types of photodynamic treatment including anti-cancer, anti-bacterial, anti-inflammatory and immune-activating applications. This project aims to develop new photosensitizers that might be classified as “immunogenic cell death inducers” in the oncological context. Ideally, any therapeutic approach aiming at cancer treatment should combine effective killing of cancer cells with the stimulation of an anti-tumor immune response, which in turn would allow the control of residual cancer cells, both at the primary tumor and/or at distant secondary lesions (metastasis). It has been demonstrated that a few photodynamic therapy (PDT) strategies can kill cancer cells in a way that stimulates an anti-tumor immune response. Therefore, this project will focus on the screening and identification of such photosensitizers and to potentiate their immunogenic capability through combination with immunoadjuvants. The final goal of this project will be to control metastatic disease, which is the main cause of death in oncological patients.

Required competencies: The candidate should fulfill all requirement listed in the general offer. She/he must have studied chemistry, biochemistry, biology or equivalent. Experience in synthesis and/or cell biological methods is desirable. Experience with in vivo will be valorized.

Starting date: September 1st 2018 Duration: 36 months Names of supervisors Dr. Ligia Silva (University of Coimbra) Prof. Dr. Mathias SENGE (Trinity College of Dublin) Job offer ESR 8

Universities involved (Double Doctorate diploma): Trinity College of Dublin (Ireland) University of Coimbra (Portugal) Employer: Trinity College of Dublin (Ireland)

Research project description and main objectives: The development of highly specific and photoactive tetrapyrrolic photosensitizers (PS) for oncological applications is a main objective of the POLYTHEA projects. In this framework, this project involves the development of a novel strategy for targeted delivery of PS to enable a rapid and specific accumulation of the PS in a solid tumor and with a level of accumulation that will allow positive therapeutic outcomes. It is based on the simultaneous targeting of cancer as well as endothelial cells from the tumor blood and lymphatic vessels.

Thus this project will be divided into two parts:

1-      Synthesis of dual-targeting PS 2-      In vitro uptake and cytotoxicity studies, both in cancer and endothelial cells, with the targeted-PS and with its non-targeted counterpart as well as bio-distribution studies

Required competencies: The candidate should fulfill all requirement listed in the general offer. He/she must have studied chemistry, biochemistry or equivalent. A strong background in synthetic chemistry and interest in in-vivo/in-vitro studies is required.

Starting date: September 1st 2018 Duration: 36 months Names of supervisors Prof. Dr. Mathias Senge (Trinity College of Dublin) Dr. Ligia Silva (University of Coimbra) Job offer ESR 9

Universities involved (Joint Doctorate diploma): UNIVERSITE de NEUCHATEL (Neuchâtel, Switzerland) UNIVERSITE de LIMOGES (Limoges, France)) Employer: UNIVERSITE de NEUCHATEL (Neuchâtel, Switzerland)

Research project description and main objectives: Rheumatoid arthritis (RA) is an inflammatory joint disease characterized by chronic synovitis, synoviocyte proliferation and, in its later stages, cartilage and bone destructions. When persistent, synovitis remains resistant to treatment by anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and intra-articular corticosteroids. Therefore, surgical removal of synovium is generally required and is not always efficient. In this context, we will design new functionalized arene ruthenium porphyrin or chlorin complexes in RA models. The combination of the photodynamic action of porphyrin with the cytotoxicity of arene ruthenium complexes has shown excellent anticancer activities under light. The main objective of this project is to provide new functionalized arene ruthenium porphyrin or chlorin complexes which will be tested in vitro on cultured synoviocytes isolated from fresh synovial biopsies obtained from RA patients undergoing arthroplasty and in vivo on rat models.

The main task will consist on preparing multifunctional linkers to combine arene ruthenium units and porphyrin or chlorin moieties and to study the chemical and photodynamic properties of the new compounds.

In vitro studies will demonstrate the pro-apoptotic and/or anti-inflammatory properties of the new compounds, as well as giving details on the signaling pathways activated in the treated cells. In vivo, collagen-induced RA models will help to demonstrate the safety and efficacy of the new metal-based drugs and to gain a better understanding of the biological distribution and the mode of action of these arene ruthenium photosensitizers in biological environments.

Required competencies: The candidate should fulfill all requirements listed in the general offer. The applicant must have a master degree (or the equivalent) in organic chemistry, with an interest in medicinal chemistry. A strong knowledge in synthetic organic chemistry is required and some experience in organometallic chemistry is an advantage but not essential. Formation and experience in biological tests in vitro and in vivo could be an advantage. At least, to be open-minded toward biological study is required. Being a multidisciplinary project, you need to be able to work independently, to have excellent collaborative skills, and to adapt rapidly to different environments.

  Starting date: September 1st 2018 Duration: 36 months Names of supervisors: Pr. Bruno Therrien (UNIVERSITE de NEUCHATEL) Pr. Bertrand Liagre (UNIVERSITE de LIMOGES) Dr. David Léger (UNIVERSITE de LIMOGES) Job Offer ESR 10