Biomedicina

1. From the lab bench to the microscope: observing the building blocks of our cells.

Sesión a cargo de: Nikolaos N. Giakoumakis (Advanced Digital Microscopy Facility)

Idioma: inglés.

Seeing is believing, and modern microscopy transformed the way that we can see the world around us. In our pursuit to comprehend complex dynamic cellular processes, it was necessary to surpass the physical limitations of our eyes. Thus, a few hundred years ago, we developed a scientific instrument to peer into the micro-cosmos around us. Light microscopy helped us discover the existence of microorganisms, shed light on the structure and the components of cells, and study the smallest parts of plants, fungi, and animals. In hospitals, microscopes help to diagnose by magnifying patients’ blood and tissue samples. Recent technological advances in computer sciences, physics and chemistry paved the way to re-revolutionising microscopes. Super-resolution microscopy is a rapidly developing field that consists of various fluorescence imaging techniques with the capacity to resolve objects below the classical diffraction limit of optical resolution. This field has given us the ability to observe the parts of subcellular structures in fixed or live samples in unprecedented detail.

In this course, students will be introduced to the principles of confocal microscopy and different super-resolution techniques. They will have the chance to prepare a sample suitable for fluorescence microscopy in order to observe the nuclei, the mitochondria and the cytoskeleton of cells in confocal and super-resolution microscopes.

2. Destroy to discover the cure – Investigating Angelman syndrome

Sesión a cargo de: Karen Sfyaki (Targeted Protein Degradation and Drug Discovery Laboratory)

Idioma: inglés.

Angelman syndrome is a complex genetic disorder affecting primarily the brain. The main characteristics of this syndrome are delayed development, speech impairment, and problems with movement and balance and, in severe cases, epileptic seizures, and sleep disorders. Currently, there is no cure for Angelman syndrome, but we know that it is caused by the loss of a protein called UBE3A. This protein belongs to the family of E3 ubiquitin ligases. These enzymes mark proteins for degradation through the proteasome. The proteasome is the cell’s trash machinery that breaks down the proteins that are damaged or that are no longer needed. Therefore, without UBE3A, its substrates cannot be degraded by the proteasome and it will accumulate. However, the substrates of UBE3A are not yet known and they could be potential therapeutic targets for Angelman syndrome.  

In recent years, a new application of the proteasome system has been developed to study proteins. Scientists have strategically managed to use the proteasome to their advantage by tricking it into degrading proteins that they are interested in. This approach is known as “targeted protein degradation”. To achieve this, we add a degradation tag to the protein of interest. This tag can be recognised by drugs called degraders, which bring the target protein and an E3 ligase closely together, so that the protein can be marked for proteasomal degradation. This technology allows us to destroy any protein of interest and discover its downstream targets.

In this course, students will add the degradation tag to UBE3A using molecular cloning techniques and become familiar with DNA quantification, cloning and bacterial transformation.

3. The art of science across scales: from spins to cells

Sesión a cargo de: Borja Mateos (Molecular Biophysics Laboratory)

Idioma: inglés.

The term 'scientist' was first coined in 1834 by William Whewell and his friends in Cambridge. In analogy to the term 'artist', the new term aimed to replace previous designations that described the job of teaching and conducting research in scientific disciplines. In fact, it remains valid to this day that great science involves a great art. The ability to reflect curiosity and creativity in one's work is of utmost importance in our profession and has significant implications for various aspects of society. The scientific method provides the framework to channel curiosity into well-defined questions and employ creativity in the necessary methodology. To address fundamental questions, it is typically necessary to characterize our system of study at various temporal and spatial scales, ranging from microseconds to years and from Angstroms to meters. Accomplishing this requires the integration of multiple disciplines, both in vitro and in vivo, as well as the expertise of numerous scientists.

Biophysics encompasses a wide range of techniques aimed at addressing fundamental questions in biomedicine, drawing upon physics, chemistry, and biology. In this course, students will learn how to employ their questions and curiosity to formulate hypotheses and design experiments. Specifically, they will gain an understanding of how a diverse set of in vitro experiments can contribute to unraveling the molecular mechanisms of diseases. This will involve the combination of atomic-resolution techniques, such as NMR spectroscopy with microscopy, and various analytical assays. As an illustrative example, the course will explore the significant role played by intrinsically disordered proteins in regulating cellular fate and potentially triggering pathogenic processes.

4. From biomedicine to computational biology

Sesión a cargo de: David Farré (Molecular Modelling and Bioinformatics Laboratory)

Idioma: inglés.

Interactions between small molecules are essential to living organisms. Amongst these molecules we find proteins and nucleic acids, whose interaction plays a crucial role in biology (e.g., in the storage, repair, expression and regulation of genetic information).

Protein-DNA interaction is defined mostly by two mechanisms, namely a direct or  base read out, or an indirect or shape readout. The former describes the ability of proteins to distinguish different binding modes. The latter focuses on the importance of certain protein and DNA sequences to adopt different 3D structures that determine the  binding sites. The relevance of these two mechanisms varies from protein to protein, but it is crucial to understand the role of a protein’s 3D structure.

In this course, students will address the 3D structure of different proteins from a computational perspective. The structure of a protein is believed to govern its function. Once the shape of a protein has been unravelled, its role within the essential biological mechanisms can be determined, thereby providing scientists with key information for the development of new methodologies that work with the shape of a given protein.

5. Chemistry in a Click!: obtaining complex molecules through easy reactions

Sesión a cargo de: Ines Maria Garcia (Research Unit on Asymmetric Synthesis).

Idioma: inglés.

Chemists have always wanted to harness the power of molecular assembly to build complex molecules and obtain the widest range of applications. The logic behind this interest is simple, as we are always in need of new molecular properties. These properties can be obtained from the joining of small molecular building blocks, which becomes more difficult as the complexity of the molecules increases.

In 2001, Barry Sharpless introduced the concept of Click Chemistry as a new approach to synthesise complex drug-like molecules by using a few practical and reliable reactions. Click Chemistry includes chemical reactions that are performed with high selectivity, high yield, and fast reaction rate, so that the “click” refers to the convenience afforded by snapping two objects together, like a luggage strap connection.

Click Chemistry has the following advantages over other types of reactions: it occurs in one pot; it is not disturbed by water; it generates minimal and usually harmless byproducts; and it has a high reaction specificity. Given these properties, this type of chemistry has been highly successful in recent years, leading its authors to won the Nobel Prize in Chemistry in 2022.

In this course, students will learn the basics of Click Chemistry and how to prepare these reactions. They will control these reactions using thin layer chromatography, detect the presence of both the reagents and the reaction products, and then finally purify the desired product.

3. NMR to study molecules in solution

Sesión a cargo de: Miriam Condeminas (Structural Characterization of Macromolecular Assemblies).

Idioma: inglés.

Structural Biology aims at understanding the shape and function of biological molecules to decipher the basic mechanisms of life. It can also help identify molecules with pharmacological applications to treat human diseases. Nowadays, such questions can be answered using a wide variety of complementary tools that include Nuclear Magnetic Resonance (NMR).

In NMR, samples are irradiated with radio waves while placed inside a strong magnetic field. As a result, frequency changes in the nuclei of the molecules can be recorded and the corresponding signals plotted into NMR spectra. By combining various types of NMR experiments, each signal can be linked to a particular nucleus and thus yield important information regarding its chemical environment. Given that these experiments can be performed in aqueous solutions, NMR is very versatile in that it enables the observation of macromolecular flexible regions, as well as dynamic processes (invisible using other techniques), and it can also map binding interfaces.

In this course, students will learn the fundamentals of NMR, how to interpret the spectra resulting from various experiments, and the workflow required for assigning a peptide.

4. Using the Protein-Eating Machine to Treat Cancer

Sesión a cargo de: Jake Antony Ward (Targeted Protein Degradation and Drug Discovery Laboratory)

Idioma: inglés.

The control of the concentration, structure and location of proteins is important for the health and fitness of our cells. When proteins are damaged or are no longer needed, they are broken down within the cell in a process known as degradation. One of the main cellular systems involved in degrading unwanted or damaged proteins is called the proteasome. The proteasome is a large structure made up of many enzymes, such as proteases, which recognise and break down these proteins. For a damaged or unwanted protein to be recognised and broken down by the proteasome, a specific label, known as ubiquitin, is usually added to the protein. Certain enzymes known as ubiquitin ligases are involved in this tagging process.

In recent years, drugs have been developed that use this proteasome system in our cells to degrade a certain protein. This is an exciting new strategy, as it can allow us to the remove a given protein from a tumorogenic cell. This approach is known as Targeted Protein Degradation (TPD). This technology works by using a drug that brings the ubiquitin ligase and the target protein for degradation closer together. The protein is thus labelled with the ubiquitin-tag and is recognised by the proteasome and destroyed. 

In this course, students will focus on a type of cancer known as Gastrointestinal Stromal Tumour (GIST). This cancer typically develops in the muscle cells of the gut. When mutated, the KIT protein is the molecule responsible for the formation and growth of this type of cancer. We are interested in designing drugs using the TPD strategy to remove KIT from GIST cancers. This line of research is exciting as it may lead to new treatments for GIST.  Students will gain hands on experience of the key techniques of gel electrophoresis and Western blotting to monitor the degradation of KIT in human cancer cells.

5. Machine learning to fight drug resistance

Sesión a cargo de: Gema Rojas (Structural Bioinformatics and Network Biology Laboratory)

Idioma: inglés.

Drug resistance, which occurs when previously vulnerable cells become unresponsive to specific drugs, poses a significant  public health concern worldwide. Antimicrobial resistance (AMR) exemplifies this issue, with estimates indicating that the annual death toll resulting from AMR could skyrocket from 700,000 to 10 million people by 2050. Similarly, drug resistance impacts the efficacy of cancer treatment, as patients may develop resistance following a relapse. The primary driver of drug resistance involves mutations in the DNA sequence of proteins associated with the drug's mode of action.

To comprehensively study this phenomenon, a crucial step involves analysing DNA sequencing data and establishing connections with protein structure and function to enhance our understanding of resistance mechanisms and devise strategies to overcome them. Machine learning has emerged as a valuable tool in predicting drug resistance by leveraging sequencing data.

In this course, students will have the opportunity to explore public databases and extract relevant biological information concerning drug resistance. They will work hands-on with sequencing data to understand the significance of mutations and observe how alterations in the sequence impact the shape and function of proteins. Finally, they will build a small machine learning model to predict drug resistance on the basis of sequence data.

1. Unravelling the Molecular Structure of Life

Sesión a cargo de: Blazej Baginski (Structural Characterization of Macromolecular Assemblies).

Idioma: Inglés.

Proteins and nucleic acids (DNA and RNA) are the basic building blocks of life. They perform a multitude of functions–from sensing, transporting, and enzymatic regulation, to building the cell’s internal skeleton. Therefore, the fold and 3D-structure of these biomolecules is carefully controlled. A protein’s 3D structure determines its activity, creates receptor binding pockets and enzyme active centres.

Crystallography is one of the few methods that allows the structural determination of such macromolecules with atomic precision. By studying the interactions of crystallised molecules by means of high energy X-rays, it is possible to pinpoint the location of atoms and their bonds in a given molecule of interest.

During this course, we will set up a protein crystallisation experiment, learn the operation of high-precision pipetting robots, and cryogenically freeze protein crystals to prepare them for X-ray data collection at the synchrotron.

2. Manipulating cellular plasticity

Sesión a cargo de: Isabel Calvo & Dafni Chondronasiou (Cellular Plasticity and Disease).

Idioma: Inglés.

The concept of cellular plasticity has gained great relevance during the last years in the context of cancer and tissue repair. Cellular plasticity allows adult cells to regress to stem cell-like states through de-differentiation pathways.

It is possible to convert differentiated cells into pluripotent stem cells (induced pluripotent stem cells or iPSCs) by the simple expression of four transcription factors. These iPSCs are functionally equivalent to embryonic stem cells (ESCs), which are derived from the developing blastocyst and can divide indefinitely while maintaining the capacity to differentiate into any cell type of the organism.

There is an increasing interest in better understanding how these transitions occur both in vitro and in vivo and how they can be manipulated. This knowledge will be directly applied in regenerative medicine to improve current medical treatments.

Students will learn the basic techniques to culture differentiated and pluripotent stem cells and they will be trained to induce the transition between cellular states. Finally, they will have the opportunity to perform in vitro assays that will help us to recognize the ultimate state of pluripotency.

3. CRISPR WARS: The Gene Strikes Backs

Sesión a cargo de: Luis Povoas (Gene Translation Laboratory).

Idioma: Inglés.

Some years ago, during the process of constructing a fly model to study human diseases our lab found a very interesting protein that seems to be responsible for many different processes in the cell. This protein is a derivate of a group of proteins responsible to introduce amino acids in tRNA, to enable protein synthesis. We called it SLIMP (seryl-tRNA synthetase-like insect mitochondrial protein). Past studies suggest that this new protein has acquired an essential function in insects, being one of the most interesting results obtained so far, the role of SLIMP in cell cycle progression. To uncover more of SLIMP’s functions, our lab is using a revolutionary technology that changed the way we make science. This technology is the CRISPR editing system. This tool enables us to precisely edit the genome of live cells. With it, we can remove genes (knock-out), introduce genes (knock-in), introduce markers to follow a specific protein (tags) and others. Therefore, with this technology, we expect to uncover SLIMP intracellular location, protein-protein interactions and try to understand the SLIMP knockdown phenotypes in relation to DNA damage and cell cycle checkpoints. During this workshop, you will be introduced to concepts of molecular cloning, cell culture and CRISPR technology. May the science be with you!

4. From biomedicine to computational biology

Sesión a cargo de: Alba Sala (Molecular Modelling and Bioinformatics).

Idioma: Inglés.

The interaction between small molecules is essential to living organisms. Amongst these molecules we find protein and nucleic acids, whose interaction plays a crucial role in biology (e.g., in the storage, repair, expression and regulation of genetic information).

Protein-DNA interaction is mostly defined by two mechanisms: what is called a direct or base read out and an indirect or shape readout. The former describes the ability of proteins to distinguish different binding modes. The later, focuses on the importance of certain protein and DNA sequences to adopt different 3D structures which determine the binding sites. The amount of importance given to these two mechanisms varies from protein to protein, but it is crucial to understand the role of a protein’s 3D structure.

In this course we will study the 3D structure of different proteins from a computational point of view. A protein’s structure is believed to dictate its function, and once a protein’s shape is understood, its role within the essential biological mechanisms can be determined; giving then information to scientists to develop new methodologies that work with a protein’s shape.

5.  Introduction to Drosophila melanogaster research: a versatile model in biology & medicine

Sesión a cargo de: Bitarka Bisai (Development and Morphogenesis in Drosophila).

Idioma: Inglés.

The fruit fly, Drosophila melanogaster, is used as a model organism to study disciplines ranging from fundamental genetics to the development of tissues and organs. Despite the obvious differences between humans and Drosophila, it is remarkable that the fruit fly shares many similarities and conserved pathways with humans. Drosophila genome is 60% homologous to that of humans, less redundant, and about 75% of the genes responsible for human diseases have homologs in flies.

Multipotency has been the focus of extensive work in biomedicine research. However, we lack much knowledge of multipotent cells in their physiological context in the full organism. During this workshop, we will address some of these issues by exploiting a naturally occurring population of multipotent cells, the adult progenitor cells (APCs) in Drosophila. In Drosophila, most larval cells, mainly polyploid, die at the transition between larval and adult stages; only the APCs survive and proceed into their terminal differentiation during metamorphosis. However, both APCs and larval cells are affected by the same nutritional and hormonal cues, suggesting that unique molecular components act in the adult progenitor cells to differentially regulate the effect of the external and the intrinsic stimuli in their unique setting.

This course provides hands-on experience of different techniques to understand Drosophila melanogaster research. You will be introduced to first steps in fly genetics through
experimentation by crossing flies, identifying genetic markers and balancer chromosomes, and applying other genetic tools used every day in the lab. We will learn about the different stages of development and the anatomy of the fly at different stages. We will also perform fly dissections and use advanced microscopy.

1. Strategies to Understand Aging and Senescence

Sesión a cargo de: Marta Kovatcheva & Valentina Ramponi (Cellular Plasticity and Disease)

Idioma: Inglés

Scientific research and modern medicine have dramatically extended life expectancy, with the average person in the 

developed world expected to reach 80 years of age or more. However, this extension in lifespan has had no effect on health span; that is, the number of healthy years a human lives. Aging is still characterised by multiple pathologies including frailty, heart disease, cancer, and neurodegenerative diseases, among many others. 

One of the main hallmarks of ageing is cellular senescence, the phenomenon by which normal cells stop dividing. Senescent cells accumulate in an organism over time, secreting pro-inflammatory molecules and contributing to age-related diseases. There is an increasing interest in clinical medicine to better identify and target senescent cells, as their elimination may delay and ameliorate some age-associated diseases. 

This course provides hands-on experience using different techniques to induce cellular senescence in normal cells. We will learn state-of-the-art techniques to study the molecular biology of senescent cells, analysing in vitro and in vivo samples. Finally, we will perform classical protocols, such as SAβgal staining, to detect senescent cells. These techniques will help us to understand, identify and target senescent cells for clearance, which is a promising therapeutic approach to extend health span.

2. Mirror, Mirror on the Wall… Who Is the Most Helpful Insect of Them All? – Getting to Know Tumorigenesis Through the Fly 

Sesión a cargo de: Elena Fusari (Development and Growth Control Laboratory)

Idioma: Inglés

The fruit fly Drosophila melanogaster has been widely used as a model organism for more than one hundred years to address biological questions in various fields. This organism has emerged as a potent tool for genetic manipulation, offering innumerable possibilities to analyze the detailed interaction between cells and tissues. 

One question could be raised: how can a tiny organism such as Drosophila melanogaster be used to understand the pathways of such a complex disease as cancer? Well, the answer is as simple as that: many biological mechanisms are well conserved across evolution, including the ones concerning pathological conditions. This is what allows scientists to translate the knowledge acquired from less complex organisms to more complex ones. For instance, 75% of human disease-related genes and 68% of human cancer-related genes have a counterpart in the fly. We are more similar to the fly than what we may think!

During this semester, we will learn how to study the complex process of tumorigenesis using this model organism, both with a local and systemic approach. We will focus mainly on carcinomas, the most common type of tumor diagnosed in humans.

Carcinomas are derived from epithelial tissue, such as the skin, and they can become invasive or metastatic by spreading beyond the primary tissue layer and surrounding tissues or organs. In aggressive cancer cells, this transition is mediated by the activation of the EMT (Epithelial to Mesenchymal Transition) program, which causes the cells to undergo morphogenetic alterations that increase invasive capacity.

In this course, we will introduce you to the first steps in fly genetics. We will cross flies, identify genetic markers and balancer chromosomes, and apply other genetic tools that we use in the lab every day in order to generate tumorigenic flies and study them. We will also learn about the anatomy of the fly in adult and larvae stages and use advanced microscopy to see several genetic markers in the tumoral tissues. We will also perform in vivo dissections and their respective immunohistochemistry.

3. Unravelling the Molecular Structure of Life 

Sesión a cargo de: Miriam Condeminas (Structural Characterization of Macromolecular Assemblies)

Idioma: Inglés

Proteins and nucleic acids (DNA and RNA) are the basic building blocks of life. They perform a multitude of functions–from sensing, transporting, and enzymatic regulation, to building the cell’s internal skeleton. Therefore, the fold and 3D-structure of these biomolecules is carefully controlled. A protein’s 3D structure determines its activity, creates receptor binding pockets and enzyme active centres.

Crystallography is one of the few methods that allows the structural determination of such macromolecules with atomic precision. By studying the interactions of crystallised molecules by means of high energy X-rays, it is possible to pinpoint the location of atoms and their bonds in a given molecule of interest.

During this course, we will set up a protein crystallisation experiment, learn the operation of high-precision pipetting robots, and cryogenically freeze protein crystals to prepare them for X-ray data collection at the synchrotron.

4. An omics complex puzzle? Let’s decipher it by using Bioinformatics!

Sesión a cargo de: Olfat Khannous (Molecular Modelling and Bioinformatics) & Marina Murillo (Gene Translation Laboratory)

Idioma: Inglés

Complex biological diseases such as cancer and Alzheimer are caused by a combination of genetic and environmental factors, and in many cases we have not yet identified or established a relationship between them to shed light to the understanding of the origin and progression of such biological problems.

Multi-omics profiling and integration combines different types of data for a better understanding of these complex diseases. 

One of the branches of the ‘Omics’ sciences is transcriptomics which involves the study of all the RNA molecules (including mRNA, tRNA, rRNA, and other non-coding RNAs) within a cell, otherwise known as the transcriptome. Consequently, by analyzing the transcriptome researchers can determine if a gene is turned on or off in the cells and tissues of an organism.

On the other hand, metagenomics is the study of the genetic material (genomes) from a mixed community of organisms of a sample. It allows us to describe which microbial communities are living within each individual (microbiome) and its relationship with host genetics, diet and environment can reveal links with disease or health.

In our workshop you will be immersed in the computational world (dry lab) understanding its synergy with the experimental lab (wet lab), and you will learn how to obtain transcriptomics and metagenomics data and also how to use bioinformatics tools to analyze them and to add missing pieces to these mentioned complex puzzles.

5. In vivo experimental approach to study breast cancer bone metastasis

Sesión a cargo de: 

Idioma: Inglés

In a primary tumor, many cells are constantly trying to enter into the circulation, travel through the bloodstream and arrive to a new organ to form a secondary tumor. This process is called metastasis and is very inefficient. However, tumor cells sometimes acquire properties that give them the ability to succeed and form a metastasis, which usually is fatal for cancer patients.

Metastasis is a very complex process, that is why we need different tools and techniques for its study. Eventhough in vitro experimentation gives us the possibility to study different aspects of tumor cells behavior inside the lab, in vivo experimentation allows a deeper understanding of how these tumor cells develop in their natural environment.

In our lab we combine all these techniques in order to study breast cancer metastasis. We use human cancer cell lines and animal models to unravel the role of specific genes in breast cancer bone metastasis.

In this course we will learn how cells are cultured and labeled in the lab, the techniques that we use to inject them into mice, how tumor growth can be monitored and the correct way to analyze the results obtained using in vivo models.