Ataxia comes from the Greek word 'a taxis' meaning 'lack of order'. Patients suffering from ataxia have problems with movement, balance and speech, and sometimes develop cognitive disabilities. These clinical symptoms significantly impair patients' quality of life, and many ataxias lead to premature death. Many ataxias have genetic origins. Although individually rare, the group of hereditary cerebellar ataxias comprises more than 100 different genetic forms, and it is estimated that there are at least 10,000 adults and 500 children in the UK alone with a progressive ataxia (Source: Ataxia UK). There are few disease-modifying drugs for ataxias available and thus, these conditions represent diseases with a significant unmet medical need. Our work focuses on the spinocerebellar ataxias (SCAs), a group of dominantly inherited disorders that affect the cerebellum, the part of the brain responsible for movement and balance. Although it is believed that SCAs are caused by the degeneration of the cerebellum over time, recent research suggests that the problem may originate from disrupted cerebellar development early in life. This project aims to better understand the mechanisms that cause abnormal development of the nerve cells in the cerebellum and contribute to the disease. We will focus specifically on the role of aberrant functioning of the metabotropic glutamate receptor mGluR1. mGluR1 is a membrane-bound receptor highly expressed in the cerebellum that plays a crucial role during normal development of this brain structure and has been linked to various SCAs. We will analyse the earliest structural, functional and molecular changes that arise from abnormal mGluR1 signalling. By understanding these early developmental disturbances, we hope to open new avenues for treatment that could delay or prevent the progression of SCA and lead to lead to improved therapeutic options for patients.

This research proposes a paradigm shift in low-cost, long-life, wireless in-situ sensing networks for the study of soil health and future sustainable agriculture. The sensing network will be enabled through wireless powering by autonomous ground and aerial vehicles. This approach will result in much lower cost underground sensors with no need for battery replacement, thus enabling data collection on far higher spatial and temporal densities than is now possible. The novel sensing network will be demonstrated in a study on the effect of irrigation with alternative water sources. With the world's population expected to surpass 9 billion by 2050, increasing food production threatens soil security, presenting one of the grand challenges of the 21st century. Sustaining high levels of food production depends on irrigated agriculture, which consumes over 70% of freshwater reserves in many regions of the world. Due to the diminishing freshwater sources, alternative water sources, for example reclaimed water, surface water, and coastal water, have been considered and used for agriculture. However, alternative water sources contain contaminants of emerging concern and/or excess nutrients and salt contents. Their impact on soil health and related contaminant effects on the soil ecosystem and productivity remain largely unknown. Therefore, there is an urgent need to develop soil sensing technologies that can effectively indicate the health condition of soils being irrigated using different alternative water resources. The prototype system developed in this project will be demonstrated in such a study, investigating effect of irrigation with alternative water sources. The research results will not only be critical for developing better soil maintenance, protection, and management practice, but also for enabling a wide range of research on soil health and associated links to sustainable agriculture. The research team plans to achieve the proposed objectives through the following tasks. (1) Develop low-power, low-cost, underground, in-situ soil sensor modules and achieve a reduction in power and cost by one to two orders of magnitude compared to commercial products. Low-power electronics in both discrete and ASIC forms will be designed and fitted to existing sensor probe technology. (2) Develop wireless power transfer and data telemetry systems that can wirelessly transfer power from a source above the ground to an underground sensor module, charging a rechargeable battery or enabling a battery-less underground sensing operation. This approach can greatly simplify the system installation and maintenance. (3) Demonstrate the proposed system operation from a controlled laboratory environment and open field testing. Sensor modules calibration and stability will be investigated to ensure long-term reliable operation. (4) Deploy the wireless sensor technology to investigate irrigation effect on soil health by using alternative water sources. Soil moisture, temperature, and salinity will be measured in-situ and collected wirelessly. Soil pH, ammonia, organic carbon and nitrogen will be measured from collected soil samples. These parameters can indicate soil intrinsic conditions due to different irrigation practices. The research will carry an important impact of soil health to address global food security and sustainable agriculture.

Ultra-Low Velocity Zones (ULVZs) are structures with strongly reduced seismic velocities at Earth's core-mantle boundary (CMB) which have been associated with or linked to hot-spot volcanism, Large Igneous Provinces, core-mantle interaction, downwelling subduction and Large-Low Velocity Provinces (LLVPs) and thus are a critical component of global mantle dynamics. ULVZs are typically studied using waveform analysis of ULVZ-sensitive seismic probes (e.g., SPdKS, ScP, ScS), but previous studies suffer from large uncertainties in ULVZ parameters due to modeling trade-offs and lack a geophysical inference of ULVZs through rigorous parameter estimation. We seek to develop a transformative waveform inversion approach and apply it to characterize ULVZ properties including their seismic velocities, density, size, and shape. Specifically, we propose to (1) collect a new database of highly ULVZ-sensitive ScP and PcP waveforms utilizing publicly available seismic array data as well as new data from South Korea, Taiwan, Japan, and the International Monitoring System (IMS) arrays, (2) advance our capabilities for full waveform Bayesian inversion for ULVZ properties in order to quantitatively distinguish regions with and without ULVZ structures (i.e., Bayesian model selection), and to perform joint inversion of ScP and PcP waveforms, (3) quantify the waveform effects from 2-D/3-D ULVZ structures, (4) search for additional, previously unlooked-for arrivals in the ScP wavefield consistent with 3-D ULVZ structure using array processing approaches, and (5) relate observed ULVZ localities and properties to lowermost mantle flow and dynamics through 3D geodynamic models.

Using new seismological observations together with mineral physics constraints, we will test hypotheses as to the origin of small scale (10 to 100 kms) heterogeneities called ultra-low velocity zones (ULVZs) at the core mantle boundary (CMB). The lowermost mantle is host to a wide variety of structures and shows heterogeneities on many scale lengths. Arguably the most intriguing seismic discovery of the last 15 years regarding the lowermost mantle is that of intermittent thin patches of extremely reduced seismic velocities near the CMB dubbed ULVZs, indicative of the existence of a 10 to 40 km thick regional basal mantle layer. ULVZs influence many aspects of mantle dynamics and it has been speculated they are the roots of mantle plumes, areas of core material entering the mantle, remnants of a global magma ocean, an influence on the path of the magnetic poles during polar reversals, and chemically distinct exotic material. Therefore, understanding the origin and properties of ULVZs is not of just academic interest, but impacts on a wide range of first-order Earth issues. Nonetheless, the origin of ULVZs remains unsolved and fundamental questions such as partial melt vs. chemical heterogeneity as source for ULVZs are still debated. To test hypotheses on the origin of ULVZs we will use a combined mineral-physical and seismological approach. Each of the proposed ULVZ models will lead to specific velocity changes, P-wave to S-wave velocity ratios and density changes for ULVZs. For instance, a partial melt origin of ULVZs will lead to a P-to-S wave velocity ratio of 1:3, while a compositional origin creates VP/VS~1-2. Currently our knowledge about ULVZ structure and lower mantle material properties is not sufficient to differentiate between these models and we will employ new seismological probes to better resolve the existent velocity and density structure of ULVZ. Furthermore, we will determine the elastic properties of perovskite and post-perovskite, as function of composition, pressure and temperature from first principle calculations to understand the elastic properties of potential ULVZ material. Identification of regions devoid of ULVZs is crucial to understand the connection between mantle flow and ULVZs. Improving the seismic coverage we will obtain a map of the CMB indicating ULVZ regions, their seismic velocities and densities. Using forward modeling based on the mineral-physics results we will be able to thoroughly test different models of origin for ULVZs.

In order to decrease the environmental impact of humanity we need to rapidly move away from the use of fossil fuels both for energy and chemical production. Hydrogen is now being pursued as an alternative energy carrier since its use yields water as a by-product (as opposed to the carbon dioxide produced when a fossil fuel is used). The challenge is therefore how we obtain molecular hydrogen (i.e., H2) in a carbon neutral manner. The conventional route for hydrogen production is known as steam reforming. This process traditionally uses a fossil fuel (i.e., natural gas) as feedstock and is an energy intensive process and so results in considerable carbon dioxide emissions. Water splitting (2H2O = 2H2 + O2) has long been viewed as an alternative option for hydrogen production but still faces some challenges, such as the process cost. It is therefore highly desirable to develop further methods for hydrogen production. In this project, we are taking inspiration from nature and considering how the use of nature's catalysts (enzymes) can assist in the production of zero-carbon hydrogen. In order to achieve this, two distinct processes must work in harmony: Step 1: Hydrogen transfer from substrate to a cofactor by enzymatic dehydrogenation. Step 2: Release of hydrogen from the cofactor so that it can be recycled back into Step 1. The 'substrate' in Step 1 is a molecule which will have two hydrogen atoms removed as a proton (H+) and a hydride (H-) by an enzyme. The hydride will then be transferred to a cofactor (known as NAD+) to yield NADH, which temporarily holds the hydride. In order for the system to be cyclic, it is therefore vital to be able to remove the hydride so that the NAD+ cofactor is regenerated and in doing so, hydrogen will be produced (via the recombination of hydride and proton). This project will therefore look to explore the use of a catalyst for this particular step. A heterogeneous catalyst (i.e., a solid catalyst) is preferred for a number of reasons. Firstly, these materials are relatively well studied and understood, easy for scaling up. Secondly, since many catalysts are based on the use of expensive metals (e.g., platinum, rhodium, gold etc) it is important to be able to separate and reuse the catalyst to decrease cost and this is far more feasible with a heterogeneous/solid catalyst. In order for the process described above to be zero-carbon it is important that the so-called substrate (which is converted into a by-product) is chosen carefully. The substrates that will be explored will be from renewable sources (i.e., naturally produced alcohols, aldehydes, acids, sugars, and polyols, etc.) and chosen such that the by-product is in its own right a value-added chemical. In other words, this project will simultaneously target the production of the key energy carrier H2 in a zero-carbon manner whilst also offering a fossil fuel free route to certain chemical compounds.