SEMESTER 1

1. Unravelling the Molecular Structure of Life 

Blazej Baginski (Structural Characterization of Macromolecular Assemblies)

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. From biomedicine to computational biology

We can recall ourselves as a set of thousands of millions of building blocks that synchronize and match in a perfect way in order to make a living organism. Those building blocks arecalled molecules and comprise four main groups in the living organisms: lipids, carbohydrates, proteins and nucleic acids. Those molecules interact in a perfect way in order to build up a higher level of complexity: cells. As a result, cells are not only the result of molecules but of a perfectly synchronized network of interactions that work extremely efficient in order to make processes such as transcription, translation, mitosis, signalling 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, modelling, and predicting the 3D structure, dynamics and interactions of nucleic acids.

In this course, we will see biomedicine from a computational perspective. Some of the diseases in the biomedical sector, including cancer, are driven by specific mutations on proteins or nucleic acids which drive an abnormal 3D structure and a lack of native protein to work as expected. Therefore, understanding the dynamics from a bioinformatic, chemistry and physic point-of-view will allow researchers develop therapeutic strategies that might serve as treatments.

3. Identifying the mechanisms regulating expression of linker histones during Drosophila embryogenesis​ 

Srividya Tamirisa (Chromatin Structure and Function)

The eukaryotic genome is tightly packed and organized into a compact nucleoprotein complex called chromatin, made up of DNA and histones. Histones are classified into two types. Core histones form the octamer core of the nucleosome and linker histones connect the linker DNA with the nucleosome. Linker histones play an important role in chromatin structure and function by binding to nucleosomes and modulating accessibility of DNA during replication and transcription. They are known to be de-regulated in several diseases and cancers. In higher organisms there are multiple variants of linker histones with redundant functions. Presence of multiple variants greatly increases the complexity of studying linker histones in vertebrates.

On the other hand, Drosophila melanogaster has only two variants, a somatic variant (dH1) and an embryonic\germline variant (dBigH1), providing an ideal model for studying these proteins. Using Drosophila as a model, we aim to understand the role of linker histones during development and disease. In this course you will learn how linker histones are implicated in development and disease along with practical training in fly genetics, dissection and immunostainings of various Drosophila tissues to look at complimentary expression of dBigh1 and dH1.

4. Manipulating cellular plasticity

Isabel Calvo & Dafni Chondronasiou (Cellular Plasticity and Disease)

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.