Structural variants (SVs) are the hidden architecture of the human genome, and are critical for us to understand diseases, evolution, and so on. The development of both sequencing technologies and... Show moreStructural variants (SVs) are the hidden architecture of the human genome, and are critical for us to understand diseases, evolution, and so on. The development of both sequencing technologies and computational tools greatly facilitates the detection of SVs, while misinterpreting or even missing complex ones. Detecting and characterizing complex events is a typical field requiring multiple disciplines, i.e., domain knowledge and computer science algorithms. In this thesis, we introduce novel algorithms to detect and validate com- plex events, and assess the reproducibility of current SV detection pipelines for clinical and research settings. Show less
This thesis systematically analyzes the physical-chemistry of lipid-graphene interactions with the major objective of reconciliating the variety of results reported in the literature. By using... Show moreThis thesis systematically analyzes the physical-chemistry of lipid-graphene interactions with the major objective of reconciliating the variety of results reported in the literature. By using five major characterization techniques typically used to study lipids, namely IR spectroscopy, ellipsometry, AFM, neutron reflectivity and QCM-D, this thesis characterizes – in details – layered structures of graphene and lipids (so called superstructures) and separately studies the dynamics of the interaction between lipids and graphene. The most remarkable result is that through the systematic construction of i) a lipid monolayer on a silicon substrate; ii) the subsequent coating with graphene and iii) the deposition of a last lipid monolayer on top of the two layers stack; graphene could be encapsulated in the hydrophobic core of a lipid bilayer for the first time, promising a range of applications to sense biological processes occurring near or inside a lipid bilayer. Show less
Microtubules are highly dynamic protein polymers that and are essential for intracellular organization and fundamental processes like transport and cell division. In cells, a wide family of... Show moreMicrotubules are highly dynamic protein polymers that and are essential for intracellular organization and fundamental processes like transport and cell division. In cells, a wide family of microtubule-associated proteins (MAPs) tightly regulates microtubule dynamics. The work presented in this thesis gives a high-resolution perspective on the microtubule assembly process and on the regulation mechanisms employed by representative MAPs. We studied dynamic microtubules outside cells, in a reconstituted minimal system. To follow microtubule growth with near molecular resolution, we developed a high-resolution technique that integrates optical tweezers, micro-fabricated rigid barriers and high-resolution video tracking of microbeads. Using this technique we found, for example, that microtubule assembly does not always occur by addition of single protein subunits, but multiple subunits could be incorporated at once at the growing end. XMAP215, a protein known to dramatically enhance microtubule growth, altered these molecular details. Another intriguing protein studied here is Mal3, a protein that is able to track growing microtubule ends. We found that Mal3 interacts differentially at the growing tip and on the rest of the microtubule, influencing all the parameters describing microtubule dynamics. In conclusion, our results give new insights into the microtubule assembly process in the absence and in the presence of regulators. Show less
