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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - Phd (Deciphering PI3K biology in health and disease)

Teaser

Summary

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. However, progress in PI3K inhibition in clinical settings must be improved, given that an in-depth understanding of target PI3K isozymes and their physiological functions in vivo is still not fully understood and only a fraction of the potential therapeutic applications have been addressed so far.
The Phd Project seeks 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) gathers 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 the ITN programme is to provide ESRs with scientific, technical and complementary skills and to establish inter-sectorial research cooperations between participants. Specifically the aims of the Phd project are:
- Scientific skills: Acquisition of state-of-the-art knowledge and technology to decipher how the PI3Ks function and translate this knowledge first into drug discovery and later to the clinics and the ability to assimilate the individual components and concepts in a goal-oriented manner.
- Basic technical skills: Provide insights into drug development, screening approaches (proteomics, lipidomics, chemical compounds, and phenotyping), microscopic techniques, image handling and management as a basis of scientific workflow up to the level of quantitative image analysis in complex environments and in vivo physiological and pathological assays.
- Complementary skills: Provide transferable skills including grant writing, scientific communication, intellectual property management, valorisation, ethical issues, project management, gender issues, and entrepreneurship.
- Establishment of international and interdisciplinary research cooperation: build links between participants to advance understanding of the different classes of PI3K isoforms and translate this knowledge into drug discovery and treatment modalities.

Work performed

The project was initiated 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 the 13th of January 2016 at the Institut dâ€™Estudis Catalans (IEC) in Barcelona, Spain.
15 ESRs have been recruited for the programme and are actively working on their projects. All ESRs are involved in network meetings and workshops, weekly laboratory meetings, courses, single-topic conferences, journal clubs, and secondments to other laboratories within the network. During the considered period, three secondments have been completed. During the lifetime of the project the ESRs benefit from training, tools and scientific advice from all collaborators.
Two annual meetings have taken place, the first one in November 2016 in London and a second one in September 2017 in Cambridge. During these meetings the students presented the progress of their projects and explained their experience within the network. During this first reporting period 2 scientific and 2 complementary workshops have been organised. The complementary workshops were on bioethics (London, 28th of November 2016) and on Science communication (Cambridge, 20th September 2017). The Scientific workshops were open to external researchers and were on New Advances in Understanding the Underexplored Isoforms of PI3K and on Signalling by p110 PI3Ks. In June 2017, the ESRs attended the PHENOMIN 2nd European School for Advanced Mouse Phenogenomics in Strasbourg, France.

Final results

The Phd network is 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, provide the potential to establish the new generation of worldwide leaders. They offer complementary scientific knowledge and technological approaches in: molecular and signalling mechanisms; physiology and pathology; preclinical models, drug development and delivery; and image analysis, transfer and manipulation. The clinical unit occupies a pioneer worldwide position in clinical trials of PI3K inhibitors, offering applicability and transferability to the proposal. The SME participating is a small-sized company developing software solutions for imaging and is trying to overcome limitations in the field of PI3K. The close collaboration amongst Phd members offers the opportunity to face the association of PI3Ks and disease from an integrative and interdisciplinary angle and is intended to start from basic science to resolve into drug development and finally support clinical trials and patient treatment improvement.
The Phd training network has impact in five areas: ESRs, industry, academia, clinical units and patient organisations. For the ESRs this cross-reactivity between different disciplines is strengthing their professional skills and enhancing their career prospects. So far the Phd programme is building synergies between researchers, generating knowledge and reagents and creating new opportunities in the clinic. We expect that the Phd network will not only have an impact on the prevention, cure and therapy of diseases with deregulated PI3K activity but also increase the international competitiveness of European research in PI3K research and drug development.