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Projects

School is organized into projects. For short description of each project and project leaders' bio read bellow.

• Physical-chemical approach: The world of “impossible” compounds
• Recombinant production of human TATA box binding protein
• Investigating high-temperature superconductivity using resistivity probe
• Drug design: the Lego block approach

Physical-chemical approach: The world of “impossible” compounds

Cubane is a unique molecule for its extraordinary C8 cage, very high symmetry, exceptional strain and unusual kinetic stability. The particular appeal of cubane, referred to as a landmark in the world of impossible compounds, stems from rehybridization of the carbon atoms away from the canonical sp3 configuration. The internuclear C-C-C bond angles sit at 90°, far from the tetrahedral angle of 109.5°, which causes huge amounts of energy to be stored within the highly strained bonds of cubane. Due to its exceptional properties there is now a revival of interest in the chemistry of cubane and its functionalized derivatives, triggered by potential application as high energy fuels, explosives and intermediates in pharmaceutical preparations.

The gas phase chemistry enables us to exclude solvent effects and study the intrinsic properties of target molecules, solving one of the fundamental physical-chemical questions: why should this reaction happen? In the given project students are going to perform a high-level computational study on the protonation of cubane in the gas phase, browsing all possible isomers and revealing plausible reaction paths. Our final goal is to relieve this strained structure and extract the energy that was captured in the cage.

Sanja is working on her doctoral thesis in physical-organic chemistry at the ETH Zurich. Her field of interests is solving mechanistic problems in organometallic catalysis. She is currently developing a method which can help understand the intrinsic reactivity of organometallic complexes. The method is specifically designed for ligand binding energy determinations by tandem mass spectrometry.

Recombinant production of human TATA box binding protein

The goal of this project is to familiarize the students with recombinant DNA technology. The task will include making competent cells prior to transforming bacteria for the expression of the human TATA box binding protein (TBP). Different bacteria strains are studied for optimal protein expression. The target protein will be extracted from the bacterial culture and subjected to qualitative and quantitative analysis on a SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis). According to the time schedule, the TBP will be purified on different affinity columns. At the end of the project, the students will summarize and evaluate the pros and cons of both different bacterial strains and purification techniques.

Shizuka started her studies of pharmacy at the University of Neuchatel, Switzerland, and finished them at the ETH Zürich in November 2002. She is now a doctoral student at the Institute for Chemical and Bio-Engineering, ETH Zürich. Her research in gene regulation systems and cellular engineering aims to optimize protein production and artificially control gene regulation in mammalian cells. Her doctoral studies also include analysis of protein expression using specific enzymatic assays, Western blot and ELISA.

Investigating high-temperature superconductivity using resistivity probe

Superconductivity, the dissipationless flow of electrical current, is a striking manifestation of a subtle form of quantum organization on a macroscopic scale. The origin of superconductivity lies in an effective attraction between the electrons. Until recently this behaviour has mainly been observed in materials under extreme conditions. In the 1980s a new class of compounds has been discovered which exhibited superconductivity at high temperatures, for example that of liquid nitrogen. This class of novel materials may provide us with further insight into quantum physics as well as numerous industrial applications. The concept of a train levitating on the rails, for instance, and thus moving without consuming energy, is not so far fetched.

In this project the students will construct and calibrate a low temperature measurement probe for resistivity of one such compound YBaCuO (YBCO). They will then perform measurements of resistivity on a batch of samples. The results will be subjected to statistical and physical analysis. The students will also learn to manipulate and obtain data using a graphical programming language – LabView.

Anna did her studies and PhD in physics at University of Cambridge. She is currently a postdoctoral researcher at the Ecole Polytechnique Federale de Lausanne (EPFL). Her research interests include emergent quantum phenomena and charge ordering in bad metals.

Drug design: the Lego block approach

Most of the human physiology depends on proteins, molecular machines that perform a dazzling array of tasks – from detecting light, helping transfer nerve impulses, producing motion and catalyzing biochemical reactions that help us derive energy from food and produce molecular building blocks of life. In diseases, some of these processes may go awry - either due to infection, environmental toxicity, or ageing. In some cases it is helpful to inhibit activity of a specific protein to cure an illness or alleviate the symptoms. The most famous drug, Aspirin, inhibits the cycloxygenase enzyme, reducing pain and inflammation.

In this project, we will focus on three proteins: cyclin-dependent kinase 2 (CDK2), coagulation factor Xa (FXa) and alpha-1a adrenoreceptor (a1a), which are targeted in treatment of cancer (CDK2), blood clotting disorders (FXa) and high blood pressure (a1a). Having at our disposal sets of known small-molecule inhibitors, we will attempt to distinguish the molecular features that make a molecule bind its target. The first (and very important) step is to develop a computer program that would numerically describe structural features of the known molecules in a variety of ways. This data is fed into a Random Forest classifier, a computer program that 'learns' how to distinguish binders from non-binders, which can later be used to screen thousands of modifications to original molecules in hope that some would be even better binders. Finally, we will use a program (AutoDock) to see how well the newly chosen drug candidates physically fit into the protein target, and visualize the hypothetical complex.

Fran did his undergraduate studies in molecular biology, and is currently a PhD student at the Laboratory for information systems, Rudjer Boskovic Institute in Zagreb. His research interests include applying new data mining techniques to various biological problems, such as genomics, protein sequence analysis and anticancer drug design.