This Blended Intensive Programme focuses on 4D Cell Biology, exploring the journey from molecular machines and sensors to disease models and their profound impact on therapeutics. It addresses the need for a comprehensive understanding of cutting-edge approaches in therapeutic development by combining insights from molecular biology, genetics, disease modelling, and drug development.

The primary objective of this course is to equip master's and PhD students with a comprehensive understanding of state-of-the-art strategies in therapeutic development. This is achieved through a collaborative effort by a team of academics with diverse expertise from multiple CIVIS European universities and African associate members.

The course is structured to integrate theoretical knowledge with practical applications and real-world insights, featuring an extensive virtual component and a one-week physical mobility to the coordinating university, Universidad Autónoma de Madrid in Spain.

The physical mobility week in Madrid offers a balanced program of teaching activities, visits to advanced research facilities (including bioimaging and preclinical units at Centro de Biología Molecular Severo Ochoa), interactions with industry (Association of biotech and pharma companies), and a workshop on drug repurposing with REMEDI4ALL. Social events are planned to foster multicultural interactions and allow participants to explore the local culture, including potential visits to nearby historic towns or Madrid's Royal Collections, and a final Spanish cuisine experience.

The physical mobility section of the BIP includes 40 hours of face-to-face activities spreaded over 5 days - between 6-10 July 2026, in Miraflores de la Sierra and Madrid (Spain).

Day 1: Advanced research infrastructure

Introduction to cutting-edge bioimaging facilities, featuring state-of-the-art microscopy and in vivo imaging platforms essential for studying and understanding physio-pathological processes:

• Centro de Biología Molecular Severo Ochoa’s Advanced Light Microscopy (facility personnel as instructors):

Objective: to provide participants with hands-on experience and a comprehensive understanding of advanced microscopy techniques, highlighting their importance in modern biomedical research.

Overview: the Advanced Light Microscopy facility at CBM offers a unique opportunity to explore how advancements in microscopy enable faster and more efficient scientific discoveries. This visit will focus on two key areas: mesoscopy and nanoscopy, demonstrating the capabilities of different microscopy techniques and their biological significance.

1. Mesoscopy: whole organ visualization is essential for understanding 3D structures, tracking development, and more. Traditional point scanning confocal microscopy faces challenges such as time constraints and photobleaching. Lightsheet microscopy overcomes these issues, providing clearer and faster imaging. Activity: participants will first observe a sample using confocal microscopy. They will then view the same sample under lightsheet microscopy. This comparison will illustrate the advantages and applications of both techniques.
2. Nanoscopy: resolution is a critical aspect of microscopy. Small structures that cannot be observed with standard confocal microscopy (e.g., spinning disk confocal) can be visualized using STED superresolution microscopy. Activity: participants will compare images obtained from both spinning disk confocal and STED superresolution microscopy. This exercise will highlight how technological advancements enhance the study of minute biological details.

High-Content Screening (HCS): while the facility currently uses fast confocals with specialized software for HCS-like methodologies, there are plans to acquire a full HCS system, such as the Operetta from Revvity, by 2026. This addition will further enhance the facility's capabilities in drug screening.

This visit to the Advanced Light Microscopy facility at CBM will provide participants with invaluable insights into the latest microscopy techniques and their applications in biomedical research. It will foster a deeper understanding of how these advancements contribute to scientific progress and innovation.

• Centro de Biología Molecular Severo Ochoa’s Preclinical Biomedicine and animal facility (facility personnel as instructors and professors Stamatakis and Reglero)

Objective: to provide participants with an in-depth understanding of the preclinical biomedicine services and animal facility at the CBMSO, highlighting the use of advanced imaging technologies.

Overview: the CBMSO Preclinical Biomedicine and Animal Facility offers a comprehensive environment for studying disease models and therapeutic interventions. This visit will focus on key areas, including the animal facility and the preclinical biomedicine service, with special emphasis on the IVIS Spectrum and the IVIM intravital microscope.

1. Animal Facility: the animal facility at CBMSO is equipped to support a wide range of preclinical studies. Participants will learn about the care, management, and ethical considerations involved in using animal models for biomedical research. Activity: tour the animal facility to understand the infrastructure and protocols in place for maintaining and studying animal models.
2. Preclinical Biomedicine Service: this service provides essential tools and technologies for preclinical research, enabling the study of disease mechanisms and the evaluation of potential therapies.
3. IVIS Spectrum: this advanced imaging system allows for non-invasive, real-time monitoring of biological processes in live animals. Participants will learn how the IVIS Spectrum is used to track disease progression, gene expression, and therapeutic responses.
4. Intravital Microscope: this powerful tool enables the visualization of cellular and molecular processes within live tissues. Participants will gain insights into how the intravital microscope is used to study dynamic biological events in real-time.

The visit to the Centro de Biología Molecular Severo Ochoa Preclinical Biomedicine and Animal Facility will provide students with valuable insights into the latest preclinical research techniques and their applications. It will foster a deeper understanding of how these advanced technologies contribute to the development of new therapies and the advancement of biomedical science.

Student project teams meet to prepare their presentations. Meetings and tutoring with professors to address questions and assess project progress.

Day 2: ASEBIO: Spanish innovation and drug discovery

• Full-day immersion in the Spanish BioTech environment. Sessions explore different approaches to identifying and developing drugs e.g., cancer treatment, including their screening processes and development pipeline. Visit the facilities of a pharma company[KS1] . Details of the sessions and the visit will be discussed in the February 2025 programmed biomedicine section member meeting.
• Student project teams meet to prepare their presentations. Meetings and tutoring with professors to address questions and assess project progress.

Day 3: REMEDi4ALL Platform workshop

• Dedicated workshop on systematic drug repurposing using the REMEDi4ALL platform, examining methodologies for identifying and validating new therapeutic applications for existing drugs across various disease contexts. Collaborators of REMEDi work packages 4, 5, and 6, such as Dr. María Laura García Bermejo, will participate in this workshop, to take place at the Cristalera site.
• Student project teams meet to prepare their presentations. Meetings and tutoring with professors to address questions and assess project progress.

Day 4: Experimental models

Comprehensive examination of various model systems, featuring visits to research facilities housing C. elegans, D. melanogaster, Zebrafish, and mouse models, with emphasis on their applications in both drug discovery and repurposing.

Sessions and participating professors:

1. Mitochondrial dynamics, defects, and mitophagy - Laura Formentini, Sara Cogliati, Konstantinos Palikaras
2. Cell culture and organoid models. From 2D to 3D - Mandeep Kaur, Elisa Carrasco, Riadh Ben Mansour.
3. Non-animal models for proteostasis, mitostasis, and aging - Margarita Cabrera, Konstantinos Palikaras, Ioannis Trougakos
4. Animal models in biomedicine - Ana Isabel Rojo Sanchís, Thorsten Schmidt, Konstantinos Stamatakis, Antonios Chatzigeorgiou.
5. Drug discovery and screening. Databases and models - Emmanuel Mikros, Gerasimos Sykiostis, Alexandru Babes, Rino Ragno.

Discussion of emerging technologies in therapeutic development, including artificial intelligence applications and network medicine approaches, concluding with career perspectives and networking opportunities.

Day 5: Integration and future perspectives

Project presentations from the students (groups of 3), each for a different disease experimental model or advanced technique application. To be evaluated by the attending professors.

The virtual consists of 42 hours of teacher-guided activities spread over 14 weeks (each Thursday) - between 15 January - 30 April 2026. The innovative teaching approach for the virtual component utilizes UAM's Moodle platform, incorporating interactive tools like Genially and Kahoot for engagement and real-time assessment, and Perusall for collaborative learning and discussion. The flipped classroom methodology will also be employed, with students working in groups to study, develop, and present on assigned topics.

January, 15: Ioannis Trougakos (NKUA), Emmanuel Mikros (NKUA), Konstantinos Stamatakis (UAM) - Presentation of the course. Perusall presentation. Student`s group assignment.

January, 22: Sara Cogliati (UAM) - “Techniques for Studying Mitochondrial Function: Bridging In Vitro and In Vivo Approaches”; Riadh Ben Mansour (Sfax U) - “Reactive oxygen species sources, localization, regulation, and effects”.

January, 29: Nicolas Boucherit and Laurent Gorvel (INSERM) - “Organoids and Microfluidic systems for the simulation of the tumor immune microenvironment” - coordinated by Anne Sophie Chretien (AMU).

February, 5: Mandeep Kaur (Wits) - "Harnessing 3D Organoid biosystems for disease modelling and advancing molecular breakthroughs". Students’ group meetings in private virtual rooms and progress supervision.

February, 12: Ioannis Trougakos (NKUA) - "The complexity, design and basic architecture of biological systems: for the subcellular to organismal level". Ana Rojo (UAM) - “Basic biology of the main in vivo model systems currently used in biomedical research”.

February, 19: Margarita Cabrera (UAM) - “Yeast as a model organism for aging and protein aggregates accumulation- related diseases”; Ioannis Trougakos (NKUA) - “Proteostasis, mitostasis and age-related diseases. Studies in Drosophila Melanogaster”.

February, 26: Konstantinos Palikaras (NKUA) - “C. elegans as a model organism for neurodegenerative diseases and mitochondrial dynamics studies“. Student group meetings in private virtual rooms and progress supervision.

March, 5: Thorsten Schmidt (UT) - "Why do we need animal models?", "Behavioral phenotyping of animal models for pre-clinical analyses". Student groups meetings in private virtual rooms and progress supervision.

March, 12: Paola Bovolenta (CBM) - “The zebrafish model in developmental and biomedical studies”. Elisa Carrasco (UAM) - "Monitoring cellular responses over time: from 2D to 3D culture models and in vivo validation in mouse models".

March, 19: Antonios Chatzigeorgiou (NKUA) - “Animal models of metabolic dysregulation”; Esteban Gurzov (ULB) “Investigating metabolic disease and liver cancer in mice”.

March, 26: Konstantinos Stamatakis and Natalia Reglero (UAM) - “Advanced light microscopy for time-resolved molecular and cellular dynamics. “Introduction to intravital microscopy”. “In vivo imaging: model and system selection and applications”.

April, 16: Emmanuel Mikros (NKUA) - “Drug Design, discovery and preclinical development”. Student group meetings in private virtual rooms and progress supervision.

April, 23: Gerasimos Sykiotis (UNIL) - “Current concepts in molecular endocrinology“. Alexandru Babes (UB) - “Pharmacology of natively and heterologously expressed Transient Receptor Potential ion channels”.

April, 30: Rino Ragno (Sapienza) - “Machine learning/ artificial intelligence applied to natural compounds for drug discovery: the case of essential oils”. Students’ group meetings in private virtual rooms and progress supervision.