3. Stepping into the world of proteins 

Jorge Garcia and Mireia Muriel (Structural biology of protein & nucleic acid complexes and molecular machines)

Proteins form the very basis of life. They regulate a variety of activities in all known organisms, from replication of the genetic code to oxygen transport, and are generally responsible for regulating cellular machinery and determining the phenotype of an organism. Proteins accomplish their tasks in the body by three-dimensional (3D) interactions between various substrates. The functional properties of proteins depend upon their 3D arrangement. The 3D structures arise because particular sequences of amino acids in a polypeptide chain fold to generate from linear chains to compact domains with specific organizations. The folded domains can serve as modules for larger assemblies or provide specific catalytic or binding sites.

Various technologies, such as X-ray crystallography, are used to disclose protein structures. This particular technique calls for the use of crystals, a material whose constituents (in this case proteins) are arranged in an ordered pattern that extend in all three spatial dimensions. Crystals subjected to this technique, scatter the x-rays, and the information collected can help to infer the protein structure.

In this course, we will use the bacteria Escherichia coli to produce a protein of interest. We will use this same protein to make crystals and observe how a real protein crystal looks like!

4. Targeting cell signaling pathways to treat cancer 

Laura Gonzalez and Nevenka Radic (Signalling and Cell Cycle Laboratory)

Cells have to constantly deal with changes in their extracellular environment. It means that they have to respond efficiently to these changes in order to prevent damage but also they have to control proliferation, survival and migration. To do that, cells have developed several mechanisms that allow them to receive, integrate and interpret signals to produce the appropriate response. These mechanisms, called ‘signaling pathways’, are based in a series of chemical changes. One of the most important modifications is phosphorylation and proteins which are able to phosphorylate others are called kinases.

Our laboratory is mainly focused in a particular protein kinase called p38 MAPK, which is activated under different stress situations and plays a critical role in inflammation, cell growth, proliferation, differentiation and cell death. However, when this pathway is dysregulated diseases such as cancer can arise. In that case, p38 MAPK inhibition could be beneficial to treat patients.

In this practical course we will provide an overview of the p38 MAPK signaling pathway and which are the main techniques we use in the lab to study it. We will use purified proteins and cultured cell lines to learn how p38 MAPK inhibitors work. Finally, we will explore which patients could benefit from them.

5. Chemical synthesis of bioactive small-molecules 

Joan Matarín and Albert Cabré (Research unit on asymmetric synthesis)

Before a medicinal drug is considered suitable for patients, it has to go through several clinical phases just to ensure its activity and safety towards our body. Even before that, millions of compounds are chemically synthetized and tested just to select the compound with more potential activity. In the pharmaceutical industry, this entire process is known as the drug development process and in its early stage, organic chemistry assumes a crucial role. At the drug discovery phase, organic chemists modulate the chemical structure of a molecule that presents biological activity to fine-tune its further potency as well as its effects in our body. Therefore, organic chemistry is the key of success when new drug candidates are designed.

In this practical course we will synthesize benzocaine (Orajel®), which is a marketed drug used as a local anesthetic. While doing so we will learn how to design a synthetic route and the main techniques/instruments that organic chemists need to synthetize bioactive small-molecules.

6. Interacting is living, living is interacting

Diego Gallego (Molecular modelling and bioinformatics)

Have you ever wondered which are the fundamental principles that explain life? Our body, a fruit fly or a flower are all formed by cells. At the same time, cells (including bacteria and even archaebacteria) are formed by four big groups of molecules: lipids, carbohydrates, proteins and nucleic acids. However, if you mix these building blocks in vitro, you won't see a cell. Obvious, isn't it? A cell is much more than the sum of its parts. To understand the whole picture, you have to know how the parts (molecules) interact between each other. When you contemplate networks of interactions, you can understand very complex processes such as transcription, translation, mitosis, metabolism, signaling pathways, etc.

The correct interaction between any two molecules (e.g. a protein and DNA) depends heavily on their 3D structure. In turn, this structure is acquired through a process of folding, guided (again) by intra-molecular interactions. One of our main interests is understanding, modeling, and predicting the 3D structure, dynamics and interactions of nucleic acids.

In the practical course, students will see biomedicine from a computational perspective. They will be challenged with a real modeling problem that will lead them to cross the boundaries between structural bioinformatics, chemistry and physics. After this experience, the take-home message will be clear: interactions are the fundamental principle that allows us to understand each and every process of life.

SEMESTER 2

1. Drosophila melanogaster as a model for studying different types of growth: From development to tumorigenesis (Part II) 

Daniela Romão and Lara Barrio (Development and Growth Control Laboratory)

Regulation of growth control is crucial for the normal development of any living organisms and for the maintenance of the homeostasis. Mechanisms such cell growth, differentiation, patterning, proliferation, programmed cell death and morphogenesis are tightly controlled during development in order to guarantee the correct formation of tissues, organs and the final anatomy and functionality of the adult animal. Drosophila is particularly well-suited for studying genetic regulation of growth control with a large variety of genetic tools available, and the ability to study tissue and cell specific defects in flies.

Besides its clear impact in development, growth regulation is also important in many genetic based diseases such as cancer. Cancer is a multi-hit process that involves mutations in oncogenes and tumor suppressor genes. This accumulation of mutations and epigenetic changes alter intrinsic cellular functions and cell-cell interactions in tissues. The conservation of signaling pathways and cellular regulatory systems between humans and flies makes the fruit fly the perfect model organism to study growth both in the context of development and of disease.

This course will be a second part of the “Drosophila melanogaster: Getting to know yourself through the fly” and because, by now, you will already be on your way to become a fly geneticist we will push you further and teach you how to mount dissected samples from both larvae and adult tissues. You will also learn how to proper image your samples using confocal microscope and process them using the correspondent statistics.

2. The role of microtubules in cell division and cancer

Joel Paz and Marta Lovera (Microtubule organization)

Cellular cytoskeleton is perhaps one of the most important structures of the cell as it is involved in several functions as morphogenesis, cellular division or cell migration. It is composed by three members, actin filaments, intermediate filaments and microtubules. Microtubules are hollow cylindric polymers composed by tubulin dimers. Microtubules are very dynamic structures that constantly undergo episodes of polymerization and depolimerization which is known as dynamic instability. Microtubules are involved in key processes as intracellular transport of cargos (proteins, vesicles and even organelles) and in mitosis where they are in charge of the formation of the mitotic spindle and proper chromosome segregation. One of the hallmarks of cancer is uncontrolled cell division and one approach to treat cancer is to try to kill cancer cells. Compounds that target microtubules disrupting the normal cell division cycle and eventually lead to cell death have been proven to be one of the most effective cancer chemotherapeutic drugs available.

In this practical course, we will learn how a mitosis occurs in vivo, what are the different phases of mitosis, what is the role of microtubules in this process and how can we treat cancer focusing on microtubules. For this purpose, we will use cultured cell lines treated with several chemotherapeutic drugs used in cancer therapy and see how they affect cell division with the help of fluorescence light microscopy techniques.