CRISPR genome editing technology is considered to become the greatest technological improvement in biomedical research since the invention of the polymerase chain reaction 25 years ago and pharmaceutical companies as well as academic research are eager to apply it. However, the efficiency of introducing defined changes into the genome by CRISPR is still low, currently limiting its application in basic research, industry and gene therapy. IMGENE unites expert European research groups of academia and industry to address by innovative and complementary approaches the low efficiency of precise genome editing using CRISPR technology. To our best knowledge, IMGENE is the only concerted approach to tackle the important problem of low genome editing efficiency of CRISPR in a multidisciplinary, intersectorial manner. The IMGENE consortium consisting of 6 academic and 1 industrial beneficiary (AstraZeneca), 2 industrial partners (Taconic; MilliporeSigma), and the patient organization Genetic Alliance, aims to improve the genome editing efficiency of CRISPR by research training of 8 ESRs to unleash the full potential of this technology. Combining complementary knowledge on protein chemistry, molecular biology, cellular biology, viral vectors, transgenic mice, gene therapy, and bioinformatics present in the network, IMGENE will establish novel tools and protocols for improved CRISPR genome editing efficiency that will be of immediate benefit for health and life science research, the pharmaceutical industry, and the application of gene therapy. In addition, IMGENE addresses crucial ethical questions related to the application of genome editing technology in animals, plants, and humans, which have to be solved to gain acceptance by the society. By excellent research training of 8 ESRs on a scientifically and economically highly relevant topic and additional training in transferable skills, IMGENE will educate novel leaders with great career perspectives in industry and academia.

INTEGRITY’s innovative approach aims to empower students in responsible research: using RCR INTEGRITY will build a teaching philosophy that underpins comprehensive research integrity training. RCR will incorporate the conventional concerns of FFP (Fraud, Falsification and Plagiarism) and questionable research practices (QRC), yet use a new orientation, namely the empowerment of students. This is vital and innovative because today’s students will encounter dilemmas that current practice cannot yet foresee but need equipment for. INTEGRITY will develop an interactive curriculum with compelling and effective tools that will be co-created with students, using key values, namely Transparency, Honesty and Responsibility. It will include innovative training and mentoring for influencers and will experiment with nudging techniques for effectiveness. INTEGRITY will build capacity in a scaffolded manner, targeting different student group levels, and will deploy training in formal, non-formal and informal contexts and cover the full range of scholarly disciplines, including computer sciences technical studies, social sciences and humanities.

Nucleotides are the building blocks of nucleic acids and have emerged as significant determinants in energy transfer and signalling. Four nucleotides are known to function as signalling molecules in bacteria, namely the cyclic mono-nucleotides cAMP and cGMP, and the cyclic di-nucleotides c-di-AMP and c-di-GMP. These molecules play specific and distinct roles in many bacterial species, and can co-exist within a single bacterial cell. Whereas the diversity of cyclic nucleotide signalling is now starting to be uncovered, very little is known about their coordination in the control of their respective signalling pathways. Specifically, in the human pathogen Listeria monocytogenes, agent of a life-threatening and foodborne disease, it is known that both cyclic di-nucleotides c-di-AMP and c-di-GMP are produced but the production of cAMP and cGMP, as well as the contribution of the four nucleotides to the virulence mechanisms deployed by L. monocytogenes is yet to be uncovered. Using multidisciplinary approaches, the present proposal aims to 1) investigate the production of cAMP and cGMP, 2) identify new signalling pathways governed by the different cyclic nucleotides, and 3) uncover their role in physiology and pathogenesis. The overall impact of this proposal can open up the field to novel concepts and provide a basis for the study of cyclic nucleotide crosstalk.