Empreinte génétique | EPFL Graph Search

Une empreinte génétique, ou profil génétique, est le résultat d'une analyse génétique de l'ADN, rendant possible l'identification d'une personne à partir d'une petite quantité de ses tissus biologiques (bulbe de cheveu, sang, salive, sécrétion vaginale, sperme). L'empreinte génétique repose sur le fait suivant : bien que deux humains aient une large majorité de leur patrimoine génétique identique, un certain ensemble de séquences dans leur ADN reste spécifique à chaque individu (en raison du polymorphisme). Ce sont ces séquences spécifiques d'un individu que l'analyse d'empreinte génétique permet de comparer. Si un échantillon de cellules présente la même empreinte génétique qu'un individu, on peut soutenir que ces cellules proviennent de cet individu, ou de son éventuel jumeau monozygote. Dans son acception initiale, l'expression empreinte génétique, de l'anglais , est formée par analogie avec les empreintes digitales utilisées dans le cadre de l'identification des criminels, qui

Multidrug-resistant tuberculosis: household transmission and associated risk factors

Laurence Läser

Given the global burden of tuberculosis, and more precisely of multidrug-resistant (MDR) tuberculosis (TB), one of the most pressing epidemiological issues is the study and prevention of transmission. The study aims to assess transmission within households that present at least two cases of MDR-TB and the possible risk factors, from MDR-TB isolates collected in Lima, Peru and further characterized by genotyping methods, spoligotyping and mycobacterial interspersed repetitive units (MIRU) - variable number tandem repeat (VNTR), used for DNA fingerprinting. Apart from the genotyping results, the data set also provides the drug susceptibility testing (DST) profile for each isolate, as well as information on the households and the patients. The key assumption to transform molecular data into epidemiological data is that all identical isolates are classified in the same cluster, the cluster belong to a unique strain of tuberculosis, and a unique strain infecting more than one individual is presumed to be the result of direct transmission. The analysis is divided in two parts, first the establishment of household transmission or outside transmission for each isolate and then the following epidemiological analysis; and requires the use of Matlab and Stata software. The main results are the cohort characteristics, the concordance between the two genotyping methods, the clusters' composition and size frequency, the transmission analysis, the amplification of resistance analysis and the risk factors analysis for household transmission. From there, the main findings are the high rate of household transmission (more than 80%) of the isolates and drug resistance amplification (up to 10 new resisitances within one household clustered strain). The risk factor analysis did not present any significant results, but a few trends that are worth to explore in the future

2010

Dynamics of Electronic and Ionic Charges in Cyanine Organic Semiconductor Devices

Sandra Christina Jenatsch

Organic semiconductor materials have been widely applied in optoelectronic devices to replace their inorganic counterparts and explore new fields of applications. Due to their high extinction coefficients, chemical tunability and solubility, cyanine dyes are an interesting class of molecules to be employed in organic semiconductor devices. Their beneficial properties have been demonstrated in organic solar cells (OSC), photodetectors and recently in organic light-emitting electrochemical cells (OLEC). The focus of this thesis is to analyse different aspects regarding the dynamics of electronic and ionic charges in cyanine based devices. Models and conclusions are not restricted to cyanine based devices but can potentially be applied in various systems where combined ionic and electronic charges are present. In order to focus on electronic processes in OSCs, a combination of steady-state, transient and impedance analysis is used. It is resolved that trapped charges can be introduced at the dye/hole extracting layer interface by using specific solvents for the cyanine layer fabrication. These measurements also reveal the low hole mobility of cyanine films which in turn limits the possible upper layer thickness in OSCs. A frequently used way to enhance the conductivity of organic semiconductors is the addition of extra charges by chemical doping. This concept is employed for a near-infrared absorbing dye which is used as donor in a bilayer solar cell. The dependence of all figures of merit versus doping concentration and layer thickness is studied in detail. It is found that the performance of the optimised cell is not further improved by doping, but that it presents a good option if thicker layers are required, e.g. on rough substrates. Furthermore, the stability and degradation pathway of the p-doped species is analysed. This information is of general relevance as they also occur after charge transfer at the heterojunction interface of an OSC and during operation of OLECs. The dynamics of ionic charge carriers is separated into two contributions. In a first step, the steady-state diffusion profile of the counter ion within a cyanine/fullerene bilayer structure is scrutinised using different profiling techniques. An unexpected constant ion profile is found throughout the C60 layer. Simultaneously, the potential within the acceptor is measured by the Kelvin probe technique. A mechanism of combined electron and ion transfer from the C60 to the dye and vice versa is proposed which is in agreement with the experimental results. A prerequisite for OLEC operation is the mobility of ionic charge carriers. Their dynamics in cyanine salts under the effect of an external field is therefore studied in such devices. Several methods are developed and applied to characterise the dynamic p-i-n structure in detail, i.e. the position and width of the intrinsic region as well as the doping concentrations in p- and n-doped regions. The combination of all these methods helps to understand the transient behaviour of these cyanine devices but can also be adapted to other OLEC systems. A major drawback of cyanine dyes as emissive material is their low fluorescence quantum yield in solid films. To overcome this restriction and improve the OLEC efficiency, host-guest systems with various visibly emitting dyes are studied. The gain in fluorescence quantum yield in the film can directly be transferred to an increase in external quantum efficiency of the device.

EPFL2017

Exploring on Protein-DNA interactions

Alexandra Styliani Kalantzi

A variety of DNA-binding proteins organizes the chromosomal DNA and regulates gene transcription, and DNA replication and recombination. In particular, for gene regulation there is a category of DNA-binding proteins, the transcription factors, which can detect and bind to a specific set of DNA motifs. For the protein-DNA complexes there are some solved structures, but for some cases, it is difficult to define experimentally these structures at the atomistic level. However, there are various in silico methods, that alone or in combination with experimental techniques, are capable of predicting proteins structures with high accuracy. DNA-binding proteins contain DNA-binding domains and unfortunately, there are few protein-DNA complexes that have been characterized at atomistic resolution. Here we have developed artificial neural networks to predict the binding sites and the interface between proteins and the DNA, based on a structure-based approach. Specifically, we used different interface descriptors and we included a variety of protein-DNA complexes, in order to predict the correct localizations of the DNA on a protein. A large group of proteins that can recognize specific DNA sequences is the KRAB-ZFP family. DNA recognition by zinc finger proteins (ZFPs) plays an important role in gene regulation. However, the molecular determinants defining the recognition of specific DNA nucleotides by ZFP finger repeats has not yet been decoded. Here, we present a method that can predict which ZF repeats specifically bind to a DNA target sequence and what is the most probable DNA target sequence for these repeats. Our method is based on the structural analysis of the binding network of resolved protein DNA complexes, and is validated on a benchmark set of solved ZFP-DNA complexes. We also characterized the binding specificity of two KRAB-ZFPs (ZFP14 and ZNF145) integrating our predictions with SMiLE-seq (Selective Microfluidics-based Ligand Enrichment followed by sequencing) data. Subsequently, we use our recognition code on ChIP-exo data, in order to give an insight into the poly-ZF domains binding patterns. We determined the most probable binding motifs and we separated the ZFPs in two groups: the ones that have a potential canonical and non-canonical binding. Altogether, this work gives an insight into the proteins that interact with the DNA, through a better understanding of the various protein-DNA interfaces and the predictions of these complexes at the atomistic level.