This proposal aims to identify novel strategies for preparing better single-molecule magnets. Single-molecule magnets are molecules that show stable magnetisation of purely molecular origin, due to their magnetic anisotropy. They are promising candidates for a bottom-up approach to magnetic data storage materials. One of the advantages is that all the molecules are the same and there is no distribution in the size of the particles. However, the blocking temperature of the magnetisation is still too low. Here we propose to study three classes of single molecule magnets that may show higher blocking temperatures: First of all, those composed of high-anisotropy ions, secondly, those containing ions with an orbital moment, and finally those containing lanthanide ions. We will study these systems using a combination of magnetometry and frequency domain magnetic resonance spectroscopy. The latter is a method that is new to the UK.

Changes in gene function, which are not caused by alterations within the gene sequence, are referred to as "modulation of gene function by epigenetic mechanisms". Epigenetic mechanisms involve addition and removal of tiny chemical groups attached to DNA and proteins. These epigenetic modifications play a key role in helping cells within the body perform the correct function. For example, brain cells and skin cells have essentially the same genes and genetic sequence, but they are fundamentally different both in structure and function, and their distinct identities need to be maintained throughout their lifetime. During development, the fertilised egg gives rise to over 200 different types of cells in the body, which accumulate epigenetic modifications and together confer an identity or signature to each cell type - these alterations are defined as their epigenetic information. Cancer cells have in essence "forgotten" their identity, and epigenetic mechanisms are thought to be involved in erasing this memory. Generally, cancer cells evolve from a so-called "cancer stem cell" into more mature cancer cells, accumulating both genetic and epigenetic mutations, which eventually confer a survival advantage to the cancer cells in response to the body's normal defences. The fundamental question is how such cancer stem cells with this "forgotten identity" arise in the first place, and to what extent epigenetic modifications contribute to this process. Recently scientists have demonstrated that tumours can be induced in the absence of genetic changes, confirming that at least in some instances only epigenetic changes, such as "forgetting identity", are sufficient to initiate cancer. We aim to identify the aberrant epigenetic changes, which can trigger a normal cell to become cancerous. Technological advances in the last couple of years have offered unprecedented potential in addressing this question. Scientists have developed a novel tool called "CRISPR/Cas9 based gene editing". With this tool we can induce a cut in the cell's DNA in essentially any region with the help of a "guide" RNA. This guide finds the sequence of interest, and recruits the enzyme Cas9 to this site to induce a cut in the DNA and generate a genetic modification. Our unique approach in inducing epigenetic mutations is that we use an inactive Cas9 enzyme which is fused to a DNA methylating (gene silencing) enzyme. In this way, wherever the guide attracts the inactive Cas9 to a DNA site, it will hypermethylate (silence) that specific DNA sequence, inducing an epigenetic change rather than a cut. Following this, we can assess the cancerous potential of cells harbouring such epigenetic changes. Cancer is associated not only with aberrant hypermethylation and silencing of some genes (as described above) but also with general loss of methylation in the cell's DNA, therefore loss of epigenetic information. Recently, I have discovered a link between signalling pathways and widespread loss of DNA methylation in mouse embryonic stem cells (which often have common features with cancer cells). In this proposal, I aim to find proteins/enzymes involved in this process. Using an embryonic stem cell model system for DNA demethylation will allow identification of factors that might play a role in general loss of methylation in cancer. As a result, we hope to find new targets which can be used in developing novel cancer drugs. Ultimately, by understanding the epigenetic basis of cancer stem-cell production, our aim is to stop cancer before it starts.

In state-of-the-art laboratories worldwide, gases of atoms are being cooled down to temperatures less than a millionth of a degree above absolute zero. At this extreme coldness, quantum mechanics takes over; the atoms lose their individual identities and become smeared out into a giant wave of matter. This quantum gas hosts a range of bizarre behaviours, from its capacity to undergo wave-like interference to its embodiment of a superfluid, a fluid with no resistance to motion. The quantum gas is far from just a scientific curiosity. It represents a clean and pure exemplar of a many-particle quantum system, giving rich insight into the quantum world. Atomic physics techniques empower experimentalists to precisely tune its physical properties and manipulate it in time and space. Due to these facets, quantum gases are being exploited as "emulators" to recreate and understand complicated physical phenomena, from superconductors and turbulence to black holes and the Big Bang. The quantum gas also holds exciting technological prospects. Their exceptional sensitivity to being disturbed is driving their development as ultra-precise sensors, e.g. of gravity, for which they are touted to lead to major advancement in oil and mineral exploration. Meanwhile, their unprecedented quantum control makes these gases candidates for performing quantum gate operations, the basis of the much-lauded quantum computer. Recent experiments in quantum gases have created a "quantum ferrofluid". Being both a superfluid and a ferrofluid, this novel state lies at the interface of two of our most bizarre fluids. Ferrofluids are liquids dispersed with tiny magnetic iron particles. Just like bar magnets, the particles interact over long-range, prefer to lie with north and south poles being adjacent, and become aligned in an imposed magnetic field. This leads to peculiar patterns and instabilities in the fluid, but, more importantly, enables the flow and physical properties to be controlled via magnetic fields, as exploited in ferrofluid technologies in medicine, information display and sealants. The quantum sibling of the ferrofluid, the quantum ferrofluid, has been formed from an ultracold quantum gas of magnetic atoms. This gas is being hotly researched to probe its novel properties and potential exploitation. Its magnetic nature extends the above-mentioned capabilities of the quantum gas into new territories, e.g., providing a testbed of quantum magnetism, emulation of systems with long-range interactions, and a sensitivity to magnetic fields which can be exploited in a new generation of magnetic sensors, with potential applications from geological exploration to military detection. Meanwhile, the long-range magnetic interaction between atoms is particularly attractive for quantum computation since it allows the computational operations to be performed at a distance. The fundamental nature of superfluidity in the quantum ferrofluid remains uncharted, and uncovering it is the core aim of this project. With superfluidity underpinning the transport properties of the system, we will reveal how the quantum ferrofluid moves and flows, swirls and gyrates, and responds to agitation. This is of fundamental interest to our understanding of superfluidity in general, but, more specifically, is of great practical benefit for future manipulation and exploitation of the quantum ferrofluid. The distinctive behaviour of conventional ferrofluids and their virtuous control via magnetic fields is suggestive of a rich plethora of novel superfluid behaviour and a new dimension of control over the superfluid state. The quantum ferrofluid may in turn provide insight into the conventional ferrofluid; being superfluid, with an absence of viscosity, the quantum ferrofluid embodies a simplified version of the ferrofluid from which outstanding problems in ferrofluids can be tackled afresh.

Biocatalysis is the application of enzymes and microorganisms to the production of chemicals for the pharmaceutical, agrochemical and bulk chemical industries. As part of the wider field of 'Industrial Biotechnology' (IB) that is making an increasing contribution to the production of essential chemicals. Biocatalysis is an attractive alternative to traditional methods of chemical synthesis in some applications as it provides processes that are environmentally benign and highly selective, in a way that many conventional catalysts are not. One example of this is the ability of biocatalysts to generate single optical isomers, or 'enantiomers' of otherwise identical chemical products, where the properties of different isomers can have vastly different effects in a biological context, such as in a drug. Researchers in the chemical industry are always looking for new biocatalysts to replace established chemical processes, and these new enzymes are often discovered in microbes. Hydratase enzymes are biocatalysts that are capable of turning one form of abundant petrochemically-derived hydrocarbons, known as alkenes, into synthetically valuable alcohols, in single isomer form, which can act as precursors for the pharmaceutical and flavour/fragrance industries. These new enzymes offer great promise, but being only recently discovered, little is known about what they look like or how they work, and further knowledge of these aspects is essential if the enzymes are to be engineered for improved activity and process suitability. In this project, we will study a new class of hydratase enzymes that not only catalyse the production of alcohols from alkenes, but are also able to take naturally occurring alcohols, and, in the reverse reaction, turn them into non-natural alkenes such as isoprene for the production of polymers including rubber. We will determine the structures of the enzymes using X-ray crystallography, and use the information to study how the enzymes work, and to inform protein engineering studies that will help us change and improve the enzymes for different applications. Finally we will, with the assistance of commercial partners, apply the improved enzymes to the transformation of useful molecules, with a view to providing new selective and sustainable methods of chemistry for industrial processes.

With my proposed research, I intend to enable future space exploration missions into our Solar System that have not been possible before. Re-entering spacecraft are exposed to extreme heat loads, which are mitigated by ablative heat shields. However, the physical processes of the extreme high speed flow around the vehicle, and the influence of the ablating heat shield on the flow are still not well understood and result in exorbitant safety margins for the heat shield mass. Heat shields become too heavy and prevent missions that suffer from high heat loads like planet exploration or sample return scenarios. I will use our new high-speed wind tunnel T6 to investigate these high-enthalpy flows experimentally, and upgrade T6 to a novel hybrid facility that enables hyper-velocity testing of models at flight temperatures that are made of real heat shield materials. T6 is newly built, commissioned in 2018, and is Europe's only facility to achieve the relevant high-speed flow conditions of up to 18 km/s. A plasma-generator will be integrated into the architecture of T6 to pre-heat models before they are exposed to the high-speed flow. This retains the characteristics of an ablation-flow coupling and allows for the first time a real ablating scaled model in an aerodynamically similar flow and enables the investigation of effects that were previously inaccessible and would make T6 the first of its kind world-wide. I plan to conduct three different types of experiments that target hypervelocity Earth re-entry: Shock layer radiation studies in a shock tube, sub-scale model testing of a re-entry capsule in a hypersonic flow field, and the upgrade of T6 to an entirely novel hybrid plasma-impulse facility. The normal shock formed in front of an entry capsule will be experimentally simulated through an equivalent shock travelling through a shock tube. The shock passes a window in the tube where it is interrogated by emission and absorption spectroscopy. This allows the spatially resolved measurement of temperatures, particle densities, and radiative heat flux. Emission measurements will be conducted with an experimental setup that is already in place, which I will extend to also include absorption spectroscopy. The Aluminium shock tube of T6 has the largest tube-diameter of current comparable facilities, which leads to a significant increase of measurement signal enabling new high accuracy data. I will target flow conditions that replicate high-speed Earth re-entry, such as encountered during the re-entry of the Japanese capsule Hayabusa. In addition, I will explore next generation mission scenarios for a Mars sample return case. The next step after the fundamental experiments of shock tube testing is moving to a full flow field around a model. The model will be equipped with surface heat transfer and pressure sensors, as well as ports for optical fibres coupled into a spectrograph. This experiment will allow the investigation of the chemically reacting flow around a real geometry and therefore represents an additional increase in complexity from the shock tube experiments. This will allow the direct comparison to a wealth of numerical simulations and direct measurements of the real flight that were captured during an observation mission. The final step in the methodology of this proposal is to bring high enthalpy ground testing to a new level. A plasma is generated and is expanded through a nozzle into the test section where the model is located. After sufficient plasma heating the model has reached flight temperature and starts to decompose. At this moment, the hyper-velocity flow is started, the plasma generator is switched off simultaneously, and the remaining plasma is flushed out by the incoming shock of the diaphragm burst. The subsequent flow now faces a model at flight temperature that reproduces important previously inaccessible effects like blowing of heat shield products, surface oxidation and surface recombination.