Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

UK CAN is the UK Cosmochemistry Analysis Network, a consortium of the main groups of laboratory-based astronomers in the UK. Monica Grady is PI, and there are 8 additional Co-Is from Imperial College, Manchester Univ, Natural History Museum and Open Univ. The aim is to allow for increased collaboration using shared resources.

Geological Disposal Facilities (GDFs) for high-level nuclear waste (HLW) and spent nuclear fuel (SNF) are based on the multibarrier concept, consisting of a metallic canister (encapsulating the HLW/SNF), an engineered clay barrier (that serves as a buffer around the canister), and the host rock, which serves as a natural barrier. Unsaturated compacted bentonite is the material generally selected to build the engineered barrier systems (EBS). The EBS will be subjected to complex thermo-hydro-mechanical and chemical (THMC) processes triggered by the heat released by the HLW/SNF, the hydration of the clay (from the surrounding rock), increments in stresses induced by progressive wetting and swelling of the compacted bentonite under highly confined conditions, and chemical interactions. Current understanding of how temperature (T) affects the hydromechanical and chemical behaviour of the clay buffer is primarily based on studies involving T up to 100 degrees C. However, authorities from different countries around the world tasked with developing and delivering GDFs recognise that enabling safe functioning at T much higher than 100 degrees C (e.g., 200 degrees C) would allow better optimisation of the design, emplacement strategies, interim storage and GDF costs. It has been observed that the swelling pressure (SP) of a Ca- bentonite (i.e., saturated with divalent cations) will tend to decrease with increasing T, but the SP of a Na- bentonite (i.e., saturated with monovalent cations) will tend to increase with increasing T. The physicochemical phenomena behind this dissimilar behaviour have yet to be investigated in detail. This is a critical research component considering both Na- and Ca-bentonites which are envisaged as potential barrier materials for the isolation of HLW/SNF. Achieving a target SP is a key to providing the mechanical protection required, and accurate prediction of this property will be essential when selecting suitable bentonites for a GDF. The overarching aim is to conduct the fundamental research necessary to optimise the type and properties of the bentonite barrier in the design of EBS at T as high as 200 degrees C. This requires better understanding of the behaviour at high T of Na- and Ca- bentonites intended as barriers, particularly when subjected to GDF conditions. This project will combine researchers from US and UK working at universities (TAMU and ICL) and national laboratories (SNL and BGS) to conduct fundamental, experimental and numerical investigations to advance the current understanding of the behaviour of Na- and Ca-bentonites intended for EBS, when subjected to very high T, up to ~200 degrees C.

Glycans are essential for life and important mediators of biological processes. Despite slowly advancing from an enigma to scientific mainstream, their biosynthesis is one of the least understood issues in cell biology. In this multidisciplinary proposal, I will develop 'precision tools' that are customized to image and map the complex processes of adding glycans to proteins in the living cell. Innovations in quantitative biology often fall short when enzymatic reactions are involved that cannot be predicted from nucleic acid sequence alone. This is a particular challenge for the addition of glycans to proteins in the secretory pathway that is mediated by the combinatorial interplay of 250 glycosyltransferases. To delineate how glycan biosynthesis is coordinated, methods are needed to inform on the functional interplay between glycosyltransferases. To address this unmet need, I will develop chemical tools as traceable reporters for the activities of individual glycosyltransferases in the living cell. These tools will allow direct insight into the large GalNAc transferase enzyme family that introduces O-linked glycans as one of the most abundant and complex protein modifications. Cutting-edge methods of mass spectrometry, super-resolution microscopy and correlative light and electron microscopy will collectively reveal which enzyme acts when and where on glycoproteins trafficking through the secretory pathway. This paradigm-shifting work is only possible through my discovery of a tactic to engineer GalNAc transferases to selectively accommodate traceable sugar analogs as substrates that are not used by wildtype transferases. The sugars proposed here are armed with chemical tags that can be traced with fluorophores. My work will thus provide unprecedented insight into the details of protein maturation in the secretory pathway, a major process in cell biology with many unanswered questions.

Breast cancer (BC) is the most common cancer in women worldwide. Estrogen receptor alpha (ERα) is the main driver in BC development and progression, and drugs inhibiting ERα are the main focus of treatment in BC. Current chemotherapies based on inhibiting ERα become ineffective when recurrent tumours develop resistance against anti-estrogens. Our work aims at finding new ways of disrupting the impact of ERα by investigating the protein on a structural level. For this, we evaluate the protein as a network and define every atom in the structure as a node, which allows us to use mathematical methods from graph-theory to investigate atomistic details. These methods have allowed us to identify novel allosteric sites and reveal new functional properties in many proteins. I want to understand the mechanistic details of ERα inhibition in cancer and the signalling paths used within the protein structure. Following on from there, I want to explore how mutated amino acids in the context of resistance manage to re-introduce functionality to the protein. By defining key allosteric sites in wild-type and mutant ERα, I aim to identify new target sites and important residues for the development of new anti-estrogens which can be used in cancer treatment.