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Binding-activated fluorescent DNA/peptide chimeric probes for cancer imaging

Final Report Summary - CHIMERA (Binding-activated fluorescent DNA/peptide chimeric probes for cancer imaging)

The overriding goal of this project is the development and the optimization of imaging tools for tumour detection through a multidisciplinary exchange of knowledge and expertise.
The three main objectives of this project are:
1) Research objective: to develop nature-inspired DNA/peptide chimeric probes for cancer imaging.
2) Training objective: to train scientists on crucial aspects of DNA biosensors and nanotechnologies, cancer targeting with peptides and cancer imaging in-vitro and in-vivo.
3) Collaborative objective: to establish and reinforce a network of international collaboration.
The development of nature-inspired DNA/peptide chimeric probes for cancer imaging will be achieved by bringing together an international and interdisciplinary group of research teams led by young promising researchers that have recently accomplished exceptional results in terms of publications and grants and by building a collaborative environment for research, innovation and technology transfer.
In order to develop DNA/peptide chimeric nanoswitches there are several key factors that should be studied. The determination of each of these aspects require a specific expertise and the involvement of each of the research groups participating in this research program. For this reason, the partners of the consortium have been selected such as to optimise the multidisciplinary and complementary expertise of the consortium on each crucial topic exposed in the proposed goals. The research groups involved in this project encompass all of the requisite expertise and, critically, have significant, demonstrated expertise in similarly complex, interdisciplinary projects. In order to reach the second objective, during the whole duration of the project a complete, complementary and balanced turnaround of visiting periods has been achieved at all the labs involved in the project.

The project’s objective was thus to allow the exchange of knowledge and expertise through training visiting periods of early stage and experienced researchers. The training involved each single aspect of DNA/peptide chimeric probes for cancer imaging. This project was also intended to help the integration and collaboration among the research teams and the establishment of a long-term collaboration between Europe and key Third Countries (USA, Canada). Despite the involvement of two partners from third countries (USA, Canada), the
consortium was able to solve most of the practical problems that occurred during the course of the project and the deliverables expected were achieved. This was possible through an important work of project management. The management of the project was a responsibility of the group leaders and in particular of partner 1 (UTV). Periodic conference calls and exchange of e-mails were established to coordinate the exchange visits in terms of research objectives and practical accommodation. Every time that the forecasted visiting periods was delayed for practical reasons alternative solutions by involving new scientists or by modifying the date of exchange were found. In this perspective the
seconded researcher was prepared in order to have a smooth settlement in the shortest possible time. This was crucial to start as soon as possible the training and experimental work. This management allowed to reach the expected results in terms of training and scientific accomplishments. Despite this, certain secondments that were forecasted in the proposal were not performed during the project.
In fact, due to both organization problems and to scientific reasons, some minor modifications have been introduced with respect to the original work plan. Of note such modifications did not:
a) Increase the total secondment of 110 researchers months
b) Change the original scope and objectives of the project
c) Change the overall balance of the secondments EU/TC and within EU.
d) Affect the achievement of the deliverables and milestones foreseen for the project period.
In the modifications that occurred during the project some of the secondments started in slightly different months than those expected in Annex I and some of the secondments were performed in different fashions that those reported in the Annex I.
At the end of the project 94.4% of the expected visits were performed. This allowed to reach most of the deliverables foreseen for the project period.
During the project’s period from November 2013 to October 2016 the joint work performed under the CHIMERA project produced important results in terms of training and scientific accomplishments.
During these 36 months project 15 researchers (experienced and early stage) for a total of 66.04 months performed visiting periods (secondments) to participating labs. Each researcher was fully trained in the field of the project and also received further general training through seminars, conferences, courses etc.
To summarize, the seconded researchers were trained in the following important fields and techniques:
1) Spectroscopic techniques, including fluorescence, absorbance and CD spectroscopies (trainer University of Rome, Tor Vergata).
2) Phage display-related techniques, such as in-vitro, ex vivo and in-vivo phage display (trainer Univ. of Tartu).
3) DNA prediction softwares such as m-fold (trainer Univ. of Montreal).
4) Most updated and cutting edge imaging techniques (trainer SBRI).
The seconded researchers, as planned in the Annex I, were also trained in more general experiences that involved the preparation of presentations in group meetings, journal clubs, language trainings and laboratory management.
The seconded researchers also achieved important scientific results and allowed to reach most of the expected deliverables of the project.
For example, visits at the participating laboratory of Prof. A. Vallée-Bélisle at the University of Montreal resulted in characterization of DNA/peptide chimeric probes and training on experimental approaches and various analytical fitting procedures that enable to determine the energy of the various states occupied by the nanodevices.
At the SBRI the seconded researchers achieved good results in tumor imaging and in the techniques related to cell culture .
The high quality of the results achieved during the project is demonstrated by the publications in high-impact journals produced in journals such as Journal of American Chemical Society and Nano Letters. The results were also presented in several international conferences.