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Deciphering PI3K biology in health and disease

Periodic Reporting for period 2 - Phd (Deciphering PI3K biology in health and disease)

Reporting period: 2017-11-01 to 2019-10-31

Phosphoinositide 3-kinases (PI3Ks) are intracellular signal transducers that regulate many biological functions like metabolism, protein synthesis, cell growth, survival, and migration. This directly involves deregulation of PI3K signalling pathway in a number of different diseases, ranging from inflammatory and cardiovascular diseases, to diabetes or cancer. The discovery of mutations in genes encoding PI3K pathway members in 80% of human cancers and in many inflammatory diseases has promoted major efforts to target this signalling pathway in the treatment of cancer and immunity.
The Phd Project sought to dissect the functions of different PI3K isoforms and translate this knowledge into new treatment modalities with PI3K inhibitors and to identify new uses for existing PI3K inhibitors. This Innovative Training Network (ITN) gathered the best European PI3K signalling research laboratories, universities, and a private company, with the objective to provide a multidisciplinary Training Programme to develop the next generation of PI3K experts and prepare talented early stage researchers (ESRs) for leading roles in research and drug discovery in European industry and academia. The objective of this ITN programme was to provide ESRs with scientific, technical and complementary skills and to establish international and interdisciplinary research cooperation between participants with the final aim of moulding doctoral candidates to experienced researchers in the PI3K field.
During the project, ESRs have developed a range of skills that have maximized their employability, they have acquired competences on the state-of-the-art technology and knowledge to decipher PI3Ks function, learnt basic technical skills that will help them during their future research career, and they have also been provided with transferable skills that have open them to greater future employment options. Moreover, during this 4 years Phd participants have strengthen or established links and research collaborations that will last beyond the Phd.
The project started with a Kick off meeting (KoM) to ensure that all participants had a complete overview of the aims and structure of the project, and to establish good relationships between the project partners. The KoM took place on January 13th, 2016 in Barcelona, Spain.
A total of 17 ESRs have been recruited for the programme. All of them were involved in the network meetings and workshops, in weekly laboratory meetings, courses, single-topic conferences, journal clubs, and secondments to other laboratories within the network.
During the lifetime of the project they benefited from training, tools and scientific advice from all collaborators. A total of 26 secondments have been performed. During these stays in other laboratories from the consortium, ESRs had the opportunity to learn new techniques and to interact, discuss and receive guidance from other PIs inside the network. These secondments together with the annual meetings have helped to create a real and solid network between the participants. Every year all members of the Phd consortium met for the annual meeting that were organized together with a scientific and a complementary workshop. Annual Meetings/workshops were set up every year by different beneficiaries and in a different place (London November 2016, Cambridge September 2017, Berlin April 2018 and Barcelona February 2019). Visiting different Institutions at each meeting have supported the career development of researchers through international and intersectoral mobility. During annual meetings ESRs had the opportunity to present and discuss the progress of their projects and explained their experience within the network. As part of the aim to provide ESRs with transferable skills the consortium organized 4 complementary workshops on bioethics, Science communication, Project and personal Management and Career Development, and as part of their scientific training ESRs also attended scientific workshops arranged by the consortium each year on different topics related with PI3K. Scientific workshops were open to external researchers. To complete their scientific training, in June 2017, ESRs attended the PHENOMIN 2nd European School for Advanced Mouse Phenogenomics in Strasbourg, France and to expose all ESRs to a non-academic ambient Arivis hosted them for a week and taught them on image analysis.
As we know the importance of the communication with the lay audience and to try to make people understand the relevance of the European research, ESRs were encourage to participate in as many outreach activities as possible: they have invited high school students to their labs to talk about their research, they have given talks to the general public, participated in the science day of their hosting cities and in the European research Night, etc
To disseminate the research results 4 papers have already been published, one has been sent for revision and at least 6 more are in preparation.
Most of the PIs extended their ESRs’ contracts in order to give them more time to finish their PhD. By now 4 fellows have already got the PhD degree and 9 will get it in the following months. The fellow settled at the SME is currently a permanent employee there and will use the experience and expertise acquired during the ITN, to develop Machine Learning tools that will be included as part of the company’s products. And the methodology described and published in an article from one of the Phd ESRs is in the process of request for a European patent.
The Phd network was composed of world-leading academic partners, translational and clinical units and an industrial partner with the joint goal of impacting on the prevention, cure and therapy of diseases with deregulated PI3K activity (cancer, neurodegenerative disease, myopathy, Cardiovascular, Infections) which are all EU health priorities. The academic partners, through their leading role in the field of PI3K, have offered complementary scientific knowledge and technological approaches in: molecular and signalling mechanisms; physiology and pathology; preclinical models, drug development and delivery; and image analysis. The clinical unit pioneer in clinical trials of PI3K inhibitors, have offered applicability and transferability to the proposal. The SME have participated developing software solutions for imaging, trying to overcome limitations in the field of PI3K.
The Phd training network has had impact in five areas: ESRs, industry, academia, clinical units and patient organisations. For the ESRs this cross-reactivity between different disciplines has strength their professional skills and enhanced their career prospects. The Phd programme has built synergies between researchers, generated knowledge and reagents and created new opportunities in the clinic. With the expertise, the knowledge and the experience acquired by Phd network members we have increase the international competitiveness of European research in PI3K research and drug development, and we expect that the results obtained will have an impact on the prevention, cure and therapy of diseases with deregulated PI3K activity.
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