3rd EuroNeurotrophin Network Week
The 3rd Training Week, initially planned to be held on September 30 - October 8th, 2020 in Siena, Italy was decided to be organised as a virtual event, due to the COVID-19 pandemic which didn’t permit travelling to Siena from the different European countries.
3rd Scientific Project VIRTUAL Meeting (October 5th – 6th, 2020)
The objective of the 3rd Scientific Project Meeting was for all participants to get an overview of the content of each WP along with the objectives, the input from partners and ESRs, the interactions with other work packages and related deliverables and milestones. It was held was held virtually on Monday - Tuesday, October 5th - 6th 2020.
The leaders of WP1 to WP7 gave a summary of the progress of each WP (Figure 17). All ESRs gave a short presentation (20 min) presenting the work performed during the first two years of their research, future plans, dissemination and communication activities, secondments and the interactions with the other ESRs. During the second day of the 3rd Scientific Project meeting, all PIs discussed the recommendations made by the expert reviewer regarding the Reporting Period I, about coordination of the compounds’ biological evaluation, about the upcoming “International Conference and Neurotrophin Cluster Day” in Crete on June 18-20, 2021, and planned the scientific papers to be prepared by the ESRs.
The leaders of WP1 to WP7 gave a summary of the progress of each WP (Figure 17). All ESRs gave a short presentation (20 min) presenting the work performed during the first two years of their research, future plans, dissemination and communication activities, secondments and the interactions with the other ESRs. During the second day of the 3rd Scientific Project meeting, all PIs discussed the recommendations made by the expert reviewer regarding the Reporting Period I, about coordination of the compounds’ biological evaluation, about the upcoming “International Conference and Neurotrophin Cluster Day” in Crete on June 18-20, 2021, and planned the scientific papers to be prepared by the ESRs.
SCHOOL - 3: Structural biology approaches for neurodegeneration
The Bioinformatics course of the EuroNeurotrophin School 3 was organized by HITS and took place online on 30th Sep – 1st Oct 2020 and was attended by all EuroNeurotrophin ESRs. During the course, Prof. Rebecca Wade gave lectures on important bioinformatics topics, such as sequence alignment, phylogenetic trees, protein pocket identification and analysis, enzyme kinetics and networks, as well as protein-protein interactions. Alexandros Tsengenes (ESR3) gave a lecture on protein structure analysis, and Christina Athanasiou (ESR4) gave a lecture on protein modelling. Alexandros and Christina also presented practical sessions in which the ESRs gained familiarity with several bioinformatics webservers. Specifically, the ESRs got hands-on experience with the Protein Data Bank, SWISS-MODEL, MetaPocket, metaPPISP, SYCAMORE, PPI-STRING, ELM, and the following tools develop at HITS: TRAPP, ProSAT+ and webPIPSA. The ESRs also had the chance to build a model of a neurotrophin by comparative modelling. In all practicals, the answers to the questions were discussed in parallel with a demonstration of the practical steps.
Bioinformatics
Crystallography
The second part of the School 3 was about Macromolecular X-Ray crystallography. The two days were organized in order to give first the basis of X-Ray crystallography and second hands-on experience on processing real diffraction data.
The first day, theorical lecture of X-Ray Crystallography was held by Prof. Mangani, explaining the crystal symmetry, the diffraction laws, the structure factor and theory behind the data processing and reduction. Then, the practical class was based on the diffraction data of the human Glutaminyl Cyclase, protein involved in neurodegenerative disease. The students had the possibility to process the data using both Mosflim and Xia2-Dials programs, and see step-by-step how the diffraction spots are indexed, integrated and merged.
The last day, lectures were about the phase problem and how to solve it, the iterative process of refinement and how to validate the protein crystal structure. Regarding the practical class, the phase problem was solved by molecular replacement using Molrep, and the structure obtained was refined by hand. Moreover, moving along the electron density maps the structural peculiarity of the catalytic sites were shown, as well as how to correctly fit the amino acids in the electron density map and how to design ligands. At the end, the Ramachandran plot, the Rfactor and Rfree obtained were explained, as being key parameters to validate the final structure.
The first day, theorical lecture of X-Ray Crystallography was held by Prof. Mangani, explaining the crystal symmetry, the diffraction laws, the structure factor and theory behind the data processing and reduction. Then, the practical class was based on the diffraction data of the human Glutaminyl Cyclase, protein involved in neurodegenerative disease. The students had the possibility to process the data using both Mosflim and Xia2-Dials programs, and see step-by-step how the diffraction spots are indexed, integrated and merged.
The last day, lectures were about the phase problem and how to solve it, the iterative process of refinement and how to validate the protein crystal structure. Regarding the practical class, the phase problem was solved by molecular replacement using Molrep, and the structure obtained was refined by hand. Moreover, moving along the electron density maps the structural peculiarity of the catalytic sites were shown, as well as how to correctly fit the amino acids in the electron density map and how to design ligands. At the end, the Ramachandran plot, the Rfactor and Rfree obtained were explained, as being key parameters to validate the final structure.
