Seminar Colour Guide:
External Faculty | External Postdoc | Company Representative Science and Society EMBL Distinguished Visitor Lecture Vision2020 Lecture Series Molecular Medicine Seminar | EIPOD Seminar | PSB Seminar | TAC Seminar Hamburg Speaker EMBL-La Sapienza Lecture
Abstract: Membranes divide cells into function-specific compartments, acting as selective permeation barriers. In order to maintain the homeostasis in cells, nutrient transport through the membrane is essential and therefore, many different types of transport proteins are found in biological membranes. Proton-dependent Oligopeptide Transporters (POTs) are members of the major facilitator superfamily (MFS), one of the largest family of transporters in living organisms, and they are responsible for the uptake of a diverse range of di- and tripeptides. These transporters are highly conserved in all kingdoms of life, also with human representatives: PepT1 and PepT2. Furthermore, these transport proteins are of harmacological interest, as they can transport a number of drugs and amino acid-conjugated pro-drugs in the small intestine.
The motivation of this research project is to obtain molecular information of the different events during a transport cycle and a detailed understanding of the promiscuous substrate recognition.
|External Faculty Speaker||
Abstract: The fundamental metric against which indicators of radiation damage are plotted is dose, the energy absorbed per unit mass of the sample. The dose can be estimated from knowledge of the beam characteristics (energy, flux, size, intensity profile) and the atomic contents of the sample (protein and solvent composition), which allows the amount of absorption to be calculated.
The program RADDOSE permitted the dose to be computed, but was not designed to take into account the rotation of the sample in the beam, since it was instigated when beams were usually larger than most crystals. The code reported the maximum dose absorbed, which was usually at the centre of the crystal if a beam with a Gaussian profile was being used. This dose could be much larger than the average dose absorbed by the irradiated volume of the crystal.
To address these issues, over the last 3 years we have written new software for temporally and spatially resolved modelling of absorbed dose, RADDOSE-3D [www.raddo.se] for particular data strategies. I will outline the features, advantages and use of this tool for macromolecular crystallography.
|Seminar given by an external postdoc||Abstract: Radiation damage to SAXS samples limits the amount of useful data that can be collected from a single sample. In contrast to the extensive analytical resources available for macromolecular crystallography (MX), there are relatively few tools to quantitate radiation damage for SAXS, some of which require a significant level of manual characterization, with the potential of leading to conflicting results from different studies. We have developed computational tools to automate and standardize radiation damage analysis for SAXS data. RADDOSE-3D, a dose calculation software utility originally written for MX experiments, has been extended to account for the cylindrical geometry of the capillary tube, the liquid composition of the sample and the attenuation of the beam by the capillary material to allow doses to be calculated for many SAXS experiments. Furthermore, a library has been written to visualize and explore the pairwise similarity of frames. The calculated dose for the frame at which three subsequent frames are determined to be dissimilar is defined as the radiation damage onset threshold (RDOT). Analysis of RDOTs has been used to compare eight different radioprotectant compounds tested at various concentrations for their efficacy of in extending the useful lifetime of SAXS samples. The results will be presented.|
|External Faculty Speaker|