Biology Projects

Diamond is looking for an enthusiastic student to develop public engagement activities for a range of visitors, using its new Visible Synchrotron (ViSR) beamline.

This placement is to develop different activities for visitors of different age ranges and experiences, from VIP visitors through to schools and universities. These activities are to cover the range from short visits of a few minutes at a time, to longer visits of up to a day, making measurements of the visible light using basic optical instruments.

Jupyter Notebooks are becoming a standard for data analysis and dissemination of results and methods.

The aim of this project is to:

Develop the interactive tools available in Jupyter (e.g. holoviews, ipywidgets) to improve how users interact with and process their data.

Develop the analysis tools for merging and analyzing this experiment data, in particular to compare and merge datasets from two different experiments.

XChem is a fragment screening facility that uses X-rays to identify fragments binding to proteins of high biological relevance (cancer treatment, bacteria resistance, infection diseases etc.). However, there is no systematic approach for the transformation of these early and weak fragments to drug-like compounds. We believe that it is necessary to get a better understanding of ligand-protein interactions which will lead to the rapid design and production of more potent compounds.

In this summer project, the student will optimise a novel/key chemical reaction so that it can be used to routinely synthesise hundreds of products. The focus will be on robust and scalable conditions that yield compounds in 30-40mg quantities.

In protein crystallography, X-ray diffraction data is recorded on a sequence of 2D images which is subsequently analysed to determine the structure of the protein of interest.

The project will seek to classify individual X-ray diffraction datasets according to a number of classifiers using machine learning that give information to software developers about the interesting aspects of the datasets from a data processing perspective.

The goal of the project is to create a software tool that besides identifying cases with pathologies and classifying them also allows developers to easily query the database to retrieve datasets with the desired features.

This project will focus on two epigenetic protein families which have been identified as potential therapeutic targets for a number of pathologies, most notably different types of cancer. The aim is to structurally characterise potential inhibitors of lysine demethylases and histone acetylases and elucidate the structural and functional relationships between these proteins and potential small molecule inhibitors, therefore aiding the process of finding potential lead molecules by structure-based optimisation that could possibly enter the steps of drug development.

The project will give the student an overview of the process leading from gene to protein crystals. It is envisaged that the student will collect X-ray diffraction data and will be trained in data analysis and structure solution. 

Flavoproteins (proteins that have a flavin co-factor) are widespread in prokaryotes and eukaryotes and catalyse a diverse range of redox reactions.

You will be tasked with producing large quantities of pure protein for structural studies and will apply the emerging technique of serial crystallography to probe the oxidation states of flavodoxin. In particular there will be opportunities to perform in situ experiments at the newly commissioned VMXi beamline to screen for diffracting crystals. You will then explore loading crystals into novel sample environments, including fixed target "chips" for serial synchrotron crystallography at the microfocus beamline. In parallel, approaches for delivering the crystals to the X-ray beam in an anaerobic environment will be developed.  

Candida albicans is an opportunistic pathogenic yeast and common member of the human microbiota gastrointestinal flora. It is usually a commensal microorganism and it resides in 40-60% of healthy adults. However, under specific conditions like in the case of immunocompromised individuals, Candida can become pathogenic, escaping from the gut tissues and invading the blood. Blood cells are the first line of defence and they eliminate Candida cells by engulfing and consequently digesting them, following a dynamic process that is called phagocytosis.

In this project we will study the clearance of Candida by heamocytes derived from Drosophila, the common fruit fly, as the innate immunity pathways between this organism and humans are highly homologous.

Transporter proteins embedded in bacterial extracellular membranes are essential for the survival of multidrug resistant pathogens that are the leading cause of hospital-acquired infections. These transporters allow bacteria to shuttle essential molecules across their oily membranes to where they are used. Alternatively, they can expel molecules such as antibiotics that would otherwise harm the pathogen. We will investigate the poorly understood TRAP protein family that transport organic acids such as succinate, pyruvate and sialic acid. These molecules are used as bacterial carbon sources or to camouflage bacteria against our immune systems. Inhibition of these transporters could lead to new therapeutics.

We will hijack the E. coli expression system to make the protein before using state of the art facilities in the Research Complex at Harwell to purify it. With our purified protein, we can attempt to grow TRAP protein crystals that will be used to investigate the protein structure using x-rays at Diamond Light Source.