TWIN2PIPSA

Three Training Schools organized by UCPH, UCAM, and TAU will complement the scientific and technical training of the FC.ID/ULisboa staff involved in the Twinning consortium, as proposed in Work Package 3 (task 3.1) "Training". These training schools aim to increase the capabilities of all partners by covering highly relevant experimental methods and skills that are important for advancing and consolidating knowledge in protein interactions and self-assembly. UCPH, UCAM, and TAU researchers will also provide local hands-on training in equipment and methods to ULisboa members through additional On-site Training events (task 3.2), which will further support the knowledge acquired in the training schools.

Training School 1 | Integrating experimental and computational approaches in protein self-assembly

Venue: Københavns Biocenter, Biologisk Institut, Copenhagen, Denmark
Dates: Nov 13-16, 2023

Objective: Introduce the network to the advanced experimental and computational techniques applied the study of proteins, their interactions, and the relationships to function and disease. Participants will acquire knowledge and practical utility of NMR and SAXS to study dynamical proteins and their assemblies; key steps involved in running molecular dynamics simulations; integration of experiments and simulations, including knowledge of key approaches and software; knowledge and data analysis of computational methods for predicting variant effects (disease mutations) using protein structure and sequence; understand the role of protein quality control in disease and experimental methods to study these; knowledge and basic overview of how multiplexed assays of variant effects can be used to study protein structure-function relationships at scale.

Day 1
● Welcome and introduction by Kresten Lindorff-Larsen
● Analyzing proteostasis by deep mutational scanning by Rasmus Hartmann-Petersen
● Protein fibrillation from a small angle X-ray scattering perspective by Annette Langkilde
● Networking event: Dinner

Day 2
● Interactions and dynamics of endogenous retroviral Gag proteins by Kaare Teilum
● Rapid protein stability prediction using deep learning representations by Lasse M. Blaabjerg
● Disordered Protein Complexes – what’s the purpose? by Birthe B. Kragelund
● Identifying functional sites at scale by Matteo Cagiada
● Visit to NMR facility by Andreas Prestel
● Data-driven modeling of the intrinsically disordered proteome by Giulio Tesei
● Combining genetic selection and microcalorimetry by Martin Willemoës
● Networking event: Harbor tour (Canal Tours, Ved Stranden, København) and Dinner

Day 3
● Multidimensional mutational landscapes of DHFR by Amelie Stein
● Visit to CPHSAXS facility by Pernille S. Tuelung
● Integrating Coarse-Grained Simulations with SAXS Data to Characterize Multidomain Proteins by F. Emil Thomasen
● Understanding intrinsically disordered proteins: from integrative modelling to design by Francesco Pesce
● ML for protein engineering by Peter Mørch Groth
● Structure–active relationship studies and microarray screening for the discovery of HDAC inhibitors by Christian A. Olsen
● Exploring non-natural trillion-peptide libraries for future therapeutics by Joseph M. Rogers

Training School 2 | From pathological protein aggregation to drug discovery

Venue: Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, UK
Dates: Jan 15-17, 2024

Objective: During the last decade, scientists from UCAM at the Centre from Misfolding Diseases developed cutting edge methodologies to study protein interactions and pathological protein aggregation. This has resulted in major scientific advances on the underlying biology that pave the way to design, develop and test novel drugs. Therefore, this training aims to introduce the fundamentals of pathological protein aggregation in protein conformational diseases, and of the development of therapeutics and diagnostics (small molecule and biologics); thus, positively leveraging the development of innovative experimental approaches with biomedical impact within the whole consortium.

Day 1
● Welcome and opening remarks by Michele Vendruscolo & Cláudio Gomes
● Antibody discovery using machine learning by Pietro Sormanni
● AlphaFold prediction of structural ensembles of disordered proteins by Faidon Brotzakis
● Protein–Lipid interactions in neurodegenerative diseases by Zenon Toprakcioglu
● Networking event: Dinner

Day 2
● Computational studies of liquid-liquid phase separation of proteins by Rosana Collepardo Guevara
● Translational chemical biology by Gonçalo Bernardes
● Aggregation of alpha-synuclein isoforms by Alexander Röntgen
● Visit to the Center of Misfolding Diseases
● Visit to the Molecular Production and Characterization Centre
● Aggregation mechanism of medin by Vaidehi Roy Chowdhury
● Molecular basis of ageing using transcriptomics by James Tomkins
● Imaging alpha-synuclein aggregates in the Parkinson’s brain by Jonathan Breiter

Day 3
● Design of knotted proteins by Sophie Jackson
● Phase separation of the Abeta peptide by Owen Morris
● Round table: Opportunities offered by twinning of twinnings - Presentation and discussion of the projects of the ULisboa PhD students by Guilherme Moreira, António Figueira, Pedro Peralta, João Sequeira, and Carina Coelho
● Closing remarks by Michele Vendruscolo

University of Copenhagen (UCPH) @ Ciências ULisboa

● Molecular dynamics studies of IDPs and their sequence ensemble relationship by Francesco Pesce (Seminar and Tutorial)
● Prediction of variant effects and residue classification via mutational scanning by Matteo Cagiada (Seminar)

● Computational tools to analyse protein stability and abundance by Thea Klarsø Schulze (Tutorial)
● Computational tools to analyse protein variant effects by Nicolas Jonsson (Seminar and Tutorial)

Workshop | Bioimaging and Spectroscopy for Protein Interactions Analysis 🔗

Venue: Faculdade de Ciências, University of Lisbon, Portugal
Dates: Sep 18-20, 2024

Day 1
● Opening session by Cláudio Gomes (Ciências ULisboa)
● Unravelling Protein Interactions and Transitions at the Nanoscale by Francesco Ruggeri (Wageningen University, The Netherlands)
● Posters session

Day 2
● Advanced Microscopy and Live Cell Imaging by Michael Lisby (UPCH)
● In Vitro and In Vivo Detection of Amyloid Structures Using Fluorescent Antibodies and Dyes by Dana Laor Bar-Yosef (TAU)
● Protein Phase Separation at the Synapse and Alpha-Synuclein Condensates by Janin Lautenschläger (UCAM)
● Protein Sample preparation for Nanoscale Analysis by AFM by Francesco Ruggeri
● Analysis of Phase Separation in Living Cells: An Experimental Overview by Janin Lautenschläger
● Networking event: Dinner

Day 3
● Extracellular Proteostasis by Michele Vendruscolo (UCAM)
● Proximity Labelling Assays to Detect Protein Interactions in Cells by Daniel Bar (TAU)
● Strategies to Design Peptide Binders for In Cellulo Protein Interaction Studies by Daniel Bar
● Closing remarks by Cláudio Gomes

University of Cambridge (UCAM)

● Tagging endogenous proteins with CRISPR/Cas9 to study protein-protein interactions by Alicia González Díaz (Centre for Misfolding Disorders, Vendruscolo Lab) - Seminar and Tutorial

Faculdade de Ciências, Universidade de Lisboa
FCiências.ID - Associação para a Investigação e Desenvolvimento de Ciências
Campo Grande 1749-016 Lisboa Portugal

Funded by the EU (TWIN2PIPSA, GA 101079147). Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the EU or European Research Executive Agency (REA). Neither the EU nor the granting authority can be held responsible for them.

Educational Resources

Training Schools

Training School 1 | Integrating experimental and computational approaches in protein self-assembly

Training School 2 | From pathological protein aggregation to drug discovery

On-site Training

University of Copenhagen (UCPH) @ Ciências ULisboa

Workshop | Bioimaging and Spectroscopy for Protein Interactions Analysis 🔗

Online Workshops

University of Cambridge (UCAM)