Applications for the 2021 Summer Placements are now closed.
Applications for our 2022 Summer Placements will open in early December 2021.
When you are in the portal, the vacancy that you are applying for is the "Summer Placements" listing, and then once in you have the opportunity to select up to three projects to apply for.
Therefore, before you apply, please read through the project descriptions listed to the left of this page, and select up to three that you would like to apply for, as applications are combined in the portal. You will be asked some general questions about yourself, and have the opportunity to select a First, Second and Third choice of project.
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In this project we aim to investigate the interplay of the cytoskeleton with lipid substructures of endoplasmic reticulum origin using correlative super resolution fluorescence microscopy and soft X-ray tomography.
A key element in the development of a cell is the constant and balanced production, upkeep and distribution of structures and vesicles tasked with particular functions such as digestion, energy production and waste disposal. The provision and distribution of these structures depend on interactions between components of the cytoskeleton (such as tubulin and actin) and the endoplasmic reticulum and they in turn respond to environmental triggers and intracellular requirements. Although evidence is accumulating on the role of the tubulin network in ER architecture, much less is known of the role of filamentous actin in ER remodelling. To date, there is no comprehensive 3D imaging data of filamentous actin architecture in action, because of the transient nature of its interactions and the difficulty in capturing relevant 3D imaging data in cells under physiological conditions.
Here we propose to use the newly developed correlative imaging platform at B24 (super resolution cryo-Structured Illumination Microscopy (cryoSIM) and cryo-Soft X-ray Tomography (cryoSXT)) to visualise the actin cytoskeleton and its contacts with the ER in established mammalian cell lines. We will work with cells that express fluorescent filamentous actin and will subject these to chemical and biological cues to study their effects on the role of the cytoskeleton.
The two microscopes we will use provide a unique imaging tool that delivers both chemical localisation through visible light fluorescence and cellular ultrastructure mapping through soft X-ray imaging.
To apply for this project, select "21001SP" on our recruitment portal.
Remember that you can apply for up to three projects in your application, if you wish.
Arthritis is defined by the uncompensated catabolism of matrix by extracellular proteases, but we have a very limited understanding of how the levels of these proteases in the extracellular matrix are kept in check or how this process is disrupted in disease.
Our recent data has unveiled a putative regulatory axis between the primary cilium, a nanoscale microtubule-based organelle and the endocytotic clearance of proteases in mouse chondrocytes. We are now exploring the hypothesis that the peri-ciliary membrane is a unique site for rapid endocytosis, conserved in evolution, particularly focusing on the narrow pit or ciliary pocket around the ciliary axoneme.
As we have no specific means to label this pocket we have combined super resolution fluorescent microscopy (using endogenous labelling of centrioles and cilium) with soft-X-ray tomography which uses natural carbon contrast to decipher the peri-ciliary membrane topography. We have high resolution 3D imaging data that clearly delineates cellular ultrastructure of primary chondrocytes and accumulated evidence using gold-and fluorophore-tagged recombinant proteases to cells that is indicative of endocytosis. This data now needs to be analysed and segmented to allow us to understand the processes that govern chondrocyte biology.
The successful candidate will work with existing data to segment and analyse cellular ultrastructure surrounding the ciliary pocket and will collect new data using the available microscopy infrastructure at beamline B24 to further understand ciliary function in primary cells.
To apply for this project, select "21002SP" on our recruitment portal.
Remember that you can apply for up to three projects in your application, if you wish.
In previous machine learning work it was noted that the low resolution limit to which diffraction data was integrated served as a strong feature when determining the chances of successful phase estimation. Initial electron density maps serve as a starting point for solvent flattening, MR or model building which ultimately result in the 3D structure of the protein of interest. The quality and reliability of these initial phases are therefore essential to boot-strap the final structure.
For this project we are looking for a candidate who can explore this topic using AI. Test diffraction data sets will be produced with varying low resolution limits and structure determination will be attempted by either MR or EP. The resulting electron density maps will then be evaluated regarding their information content, i.e. whether the details visible will allow for model building or not.
The diffraction data used is available from an in-house database, METRIX, which has been developed for machine learning purposes and the resulting electron density maps will have been created for this project in advance. The candidate will hence focus on training a cNN, ResNet or related alternatives in distinguishing interpretable maps from non-interpretable ones.
To apply for this project, select "21003SP" on our recruitment portal.
Remember that you can apply for up to three projects in your application, if you wish.
XChem is a fragment screening facility that uses the X-rays to identify fragments binding to proteins of high biological relevance (cancer treatment, bacteria resistance...). Every day, 500 fragments can be analysed per protein, and new fragments hits are discovered. However, there is no systematic approach for the progression of these weak fragments to drug-like compounds.
The XChem group has sought to address the downstream bottleneck with a liquid handling robot for automated high-throughput synthetic chemistry. Costs and time savings compared to conventional bench chemistry would allow the testing of 100s of compounds when only a handful are currently investigated. We believe that it is necessary to get a better understanding of ligand-protein interactions for a rapid design and production of more potent compounds.
In this summer project, the student will use a photo-chemical reaction within a four-step sequence to synthesise 100s of follow-up compounds derived from a fragment hit obtained during the screen of a protein. The focus will be on establishing a protocol for automating several reactions with the liquid handler that will reliably yield products in 30-40mg quantities. These follow-up compounds will then be screened by X-ray, providing crucial data on the binding mode of the ligands.
In the event of stringent lab restrictions next summer, the project will refocus on the remote multi-step coding of the robot and less experimental synthesis in the lab.
To apply for this project, select "21004SP" on our recruitment portal.
Remember that you can apply for up to three projects in your application, if you wish.
Water is one of the most important industrial chemicals. It is both the most common solvent in in the chemical industry, and the most common cause of corrosion. Therefore, understanding how water interacts with the surface of materials is of paramount importance. Yet, our techniques that are most sensitive to the surface typically must be performed in a vacuum, at best, exposing the sample to water vapour, but rarely liquid water. Trying to expose our samples to liquid water in air, prior to measurement, results in unintended atmospheric contaminants being deposited onto the sample potentially completely changing the surface chemistry. In this studentship, the successful student will join the I09 beam line at Diamond Light Source to test a “cold finger” deposition system that allows purified water to be crystallised into ice onto a cold finger, the water is then allowed to melt onto the sample. This allows ultra-clean exposure to liquids and control over what, if any, contaminants are introduced.
The student will then participate on a beam time on the I09 beam line, which offers world unique capabilities in studying the structure of the surface of materials, to study titanium dioxide after exposure to an ultraclean water droplet.
To apply for this project, select "21005SP" on our recruitment portal.
Remember that you can apply for up to three projects in your application, if you wish.
The XChem platform is an established, successful, high-throughput pipeline offered to Diamond users (academic and industrial) for screening of small molecules for drug discovery. XChem allows users to soak 100’s of protein crystals with different small compounds, with the diffraction data collected on the associated beamline, I04-1. Traditional protein crystal soaking methods would take months to screen a compound library, this can be achieved in a week in XChem.
There is high demand for XChem from biotech and pharmaceutical companies and they are generally very happy with their results – it is not unusual for industrial users to bring their follow up compounds back to the platform. However, they do raise points about the process that have not been addressed. One recurring concern is the potential for false negatives.
Our current protocol involves soaking a protein crystal at a high compound concentration for a defined period of time. In order to rapidly screen hundreds of compounds, we use one crystal per soaking condition for data collection. However, some crystals do not survive the compound soak, either disintegrating during the soaks or failing to diffract in the X-ray beam. So we can surmise that the fragment had a powerful effect on the crystal, but don’t know how relevant the interaction is.
Industrial users have raised concerns over these misses. Are they genuine negatives? If you used different soaking conditions would you see the same results? If you collected data from more crystals, would the same thing happen? Are we missing interesting compounds?
This project aims to address these questions. The student would gain a fully immersive experience of fragment-based crystal screening and be guided through designing and performing experiments to seek the answers. They would work primarily with the industrial XChem team, but also the academic XChem and I04-1 teams.
To apply for this project, select "21006SP" on our recruitment portal.
Remember that you can apply for up to three projects in your application, if you wish.
The field of structural biology is currently undergoing a rapid development. Serial crystallography has opened up many new opportunities as it enables to record multiple diffraction patterns from a continuous supply of protein microcrystals. The advantages of serial approaches enable us to a) collect data on crystals that are otherwise too small, b) limit the effects of radiation damage by spreading the applied dose, c) provide the opportunity to derive structural information under physiological conditions, and d) provide an opportunity for time-resolved experiments at synchrotrons and X‐ray free electron lasers (XFELs). Sample preparation and presentation impose unique challenges on serial experiments and are one of the factors that limit effectiveness of data collection. This can be particularly challenging for biological systems that require very specific working conditions, i.e. are temperature, oxygen or light sensitive.
As part of the ongoing research efforts, XFEL Hub together with the University of Oxford and the I24 team have been working on the development of a generalizable strategy in which serial data could be collected from protein microcrystals under anaerobic conditions. In our recent study (Rabe, P. et al., IUCrJ, 2020, 7, DOI: 10.1107/S2052252520010374), we have presented a new method based on the fixed target mount developed by the I24 team. To provide optimal, oxygen-free environment, we developed a way to prepare samples under anaerobic conditions in holders that were modified to minimize air penetration. We further validated this modified design by developing a fluorescence-based assay and directly demonstrated its application on three different biological systems.
As our design does not offer perfect impermeability, in the future we would like to introduce further modifications to our system which would aim at improving gas penetration properties. The role of the student will be to characterize the new designs. At the beginning the student would learn how to operate the main equipment to be used (anaerobic chambers and spectrophotometer) and how to prepare, handle and load the samples into the standard and anaerobic fixed target holders. The next step of the project would include assembly of different mounts and sealing material suggested by the supervisor and the student in the anaerobic chamber. The student would test gas impermeability of the mounts and sealing material in spectroscopic measurements using an oxygen-sensitive fluorescent compound. In the next step the different mounts and sealing materials would be examined with samples provided by the collaborators within the XFEL Hub BAG time, during X-ray data collection.
At the end of the placement the student will be asked to give a presentation and provide the final report in a written form to the supervisor.
To apply for this project, select "21007SP" on our recruitment portal.
Remember that you can apply for up to three projects in your application, if you wish.
Soft X-ray spectroscopies, such as X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS) allow determining the chemical state of a sample’s near-surface region. Biologically relevant interfaces are an area of research that is largely unexplored with these methods, but could potentially benefit immensely from more surface-specific information.
The aim of the project is to use Near Ambient Pressure (NAP) XPS and XAS to explore the interaction of trehalose and water. Trehalose is a sugar formed by two glucose molecules which are linked by an oxygen atom. It is a very effective protective agent allowing plants to survive in harsh environmental conditions such as drought and/or extreme temperatures. The governing mechanism is believed to lie within the nature of the hydrogen bonding between the water and the sugar molecules. XPS and XAS are both very well suited to study hydrogen bonding and their application to this system will provide new insights into the mechanisms of the protective properties of this molecule.
To apply for this project, select "21008SP" on our recruitment portal.
Remember that you can apply for up to three projects in your application, if you wish.
Plastic litter is a major global environmental problem with unknown consequences such as their breaking down into hard-to-detect microplastics. While these microplastics may be cytotoxic to (micro)organisms, they can also sorb hazardous chemicals and materials, enhancing their potential toxicity. To date, the likely adsorption of commercial engineered nanomaterials into microplastics’ surfaces is unreported, leaving open the question of whether these complexed are being formed and their environmental risks.
In this project, a batch of incubation experiments of commercial microplastics with nanomaterials are proposed. Commercial micro-polyethylene will be used as widely available plastic-monomer, while both ZnO and TiO2 nanomaterials will be studied because of their huge worldwide production. A range of incubation conditions will be evaluated: i) time (up to 3 days), ii) illumination (light/dark) and iii) temperature. The microplastics will be recovered by filtration and further studied by X-ray Fluorescence (XRF) and Scanning Electron Microscopy coupled by Energy Dispersive X-ray spectroscopy (SEM-EDX) analyses. The XRF will be performed on the isolated microplastics to assess the extent of zinc and titanium adsorption into the microplastics surface. Selected samples will be later measured by SEM-EDX, allowing to image microplastics morphology changes and the location where the nanomaterials adsorption had taken place.
To apply for this project, select "21009SP" on our recruitment portal.
Remember that you can apply for up to three projects in your application, if you wish.
Beamline I16 is a world leading instrument for studying subtle properties of novel materials, from charge-ordering in superconductors to antiferromagnetism in Mott-insulators, and so much more besides! The versatility of this instrument is due in part to the large 6-axis diffractometer that can rotate a sample, or sample environment, through almost any orientation and position a suite of detectors at a range of useful positions for diffraction experiments. The diffractometer is essentially a large, heavy robot that moves in specific directions very precisely (for more info Google “Diamond I16” or “Kappa Diffractometer”). The many axes of the diffractometer mean that visualising its movements can be a challenge, with the potential for damaging collisions always a possibility. Indeed, users and staff have previously been known to draw diagrams and make models to pre-empt its motion!
In this project, you will create an interactive 3D model of the 6-axis diffractometer using a combination of python programming and 3D visualisation software. The aim is to create a piece of software that can be used by anyone on the beamline to simulate motions of the diffractometer, anticipating collisions and beneficial diffraction conditions for experiments. You will be free in your choice of solution but will have guidance on the working of the diffractometer and design of the software. You will have access to CAD drawings of the diffractometer and the mathematical formulas that define the movement of the diffractometer. If it is possible you will have the opportunity to see the beamline in action and work with the beamline team on experiments and testing. Working on a synchrotron x-ray beamline can be challenging and stressful but also highly rewarding!
To apply for this project, select "21010SP" on our recruitment portal.
Remember that you can apply for up to three projects in your application, if you wish.
Diamond Light Source is a national facility which produces intense X-ray beams for scientific research in a wide range of fields, from physics to archaeology. In order to produce accurate results these X-ray beams need to be as stable as possible. The first and most important step in keeping the beam stable is being able to accurately measure where it is! To do this, we use a variety of measurement instruments, including fast, 600fps, X-ray cameras; photoelectric intensity monitors that measure the edges of the beam; and even synthetic single-crystal diamonds.
The aim of this project is to develop a method to synchronously trigger multiple instruments and capture fast X-ray beam position data simultaneously, at different locations on the beamline. Before reaching the sample, the X-ray beam is focused and shaped by monochromators, slits, and mirrors. By making synchronous observations of fast beam movements at different locations along the beam path, identification of specific components introducing beam movement and vibrations can be made.
The student’s time will be spent understanding the experimental equipment with a hands-on approach in the lab, making hardware to trigger data acquisition, collecting measurements on the beamline, and finally developing a software tool which can be used to analyse the data acquired. Being able to find correlated motion that is measured on all instruments and uncorrelated motion that is only measured on one instrument is extremely useful in finding the source of beam motion. This work will help Diamond to find the uncorrelated motion along the beam path, better understand where beam motion originates, and help us improve our beamlines.
To apply for this project, select "21011SP" on our recruitment portal.
Remember that you can apply for up to three projects in your application, if you wish.
Scientific experiments at Diamond produce vast quantities of data. Storing sufficiently rich information about the experiment and associated samples (i.e. metadata) is essential to exploit the results. Providing effective tools for scientists to analyse the results is also essential to the scientific process.
This project is looking to integrate effective web based data visualisation tools for users of the Diamond facility. The solution proposed is to make use of a web based data visualisation tool developed by the MAX IV institute in Sweden. This tool is specifically designed to open, view and interpret a standard scientific data file format (HDF5/nexus). The challenge is to integrate this into Diamond computing infrastructure and its web based Laboratory Information Management System (LIMS).
A successful outcome will allow Diamond's users to access state of the art visualisation tools as part of our standard toolkit. This will allow scientists to assess their results faster and more effectively than before, supporting the scientific research conducted at our facility.
To apply for this project, select "21012SP" on our recruitment portal.
Remember that you can apply for up to three projects in your application, if you wish.
Diamond Light Source is the UK's national synchrotron science facility, located at the Harwell Science and Innovation Campus in Oxfordshire.
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