RRID: RRID:SCR_011119 , RRID:nlx_78440
FundRef: 501100021082
ISNI: 0000000123240507
Wikidata: Q375606
RRID: RRID:SCR_011119 , RRID:nlx_78440
FundRef: 501100021082
ISNI: 0000000123240507
Wikidata: Q375606
The core components of executive functioning (EF) - inhibitory control, working memory and switching -are the basis for planning, reasoning and problem-solving. EF associates cross-sectionally and longitudinally with academic achievement. Weaker EF is common in developmental disorders, as well as in low SES children. Several EF training interventions have therefore been developed, with a view to improve academic outcome, with varied success. This PhD involves two main elements. First, a systematic literature review or meta-analysis of prior work investigating the impact of different types of physical exercise on EF in childhood will be carried out to identify key ingredients of successful interventions. Second, a novel school-based dance initiative combining physical exercise (dancing) with cognitive training (creativity) will be evaluated. The organisation Creativity, Culture and Education will run a randomised control trial (RCT) with Year 5 children (9-10-year-olds) in 40 primary England schools. I will work with my academic supervisor to (1) advise on the design of the RCT, in particular the identification of a suitable active control intervention, and (2) select and carry out pre-, post- and long-term follow up assessments to allow new specific questions to be answered on the causal pathways between physical activity, creativity and EF, and more distal school attendance, engagement and attainment outcomes. This project is pertinent to the ESRC sustainability, prosperity and well-being research theme. The UN has projected a significant increase in the world's population (2018: 55%, 2050: 68%) living in urban areas by2050; in parallel, child poverty in the UK increasing (2018: 30%, 2019: 37%). An activity which can be carried out in urban settings, involves physical exercise and leads to improvements in EFs and broader outcomes has the potential to be adopted by education policy makers and improve well-being and labour market success for children, particularly low SES children.
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The goal of this proposal is to obtain mechanistic insight the microtubule-based transport system that enables cilia/flagella to assemble and perform essential functions in cell motility, signaling, and sensing. Strikingly, this process of intraflagellar transport (IFT) involves multi-megadalton polymers, termed IFT 'trains', which move under the power of oppositely-directed microtubule motors dynein-2 and kinesin Kif3. To address outstanding motor mechanisms of IFT, I propose a multi-disciplinary approach spanning three scales. At the scale of individual motors, we will determine structures of the dynein-2 and Kif3 complexes to elucidate how their subunits come together and enable regulated motor activity. At the scale of multi-motor assemblies, we will reconstitute IFT trains with purified proteins to dissect how they polymerize and coordinate bidirectional motility. At the scale of whole cilia, we will determine how dynein-2 powers IFT turnaround at the ciliary tip and define spatial regulators of dynein-2 in mammalian cells. To achieve these goals, we will use reconstitution and cryo-EM to determine structures, fluorescence microscopy to visualize dynamics, and genome editing to interrogate cellular factors. Together, these studies will illuminate the multi-scale mechanisms that cells use to build and signal through cilia/flagella, which I will integrate into a molecular movie. To swim, move fluids, and sense their environment, eukaryotic cells construct long, slender organelles on their surface known as cilia. Defects in cilia are associated with a wide range of severe human developmental disorders. Many of these conditions can be traced to failures in a transportation system that moves building blocks and signalling molecules to and from the site of assembly at the ciliary tip. Using a multi-disciplinary approach, I aim to understand the structural mechanisms of the molecular motors powering this system, how they assemble into multi-motor trains, and how these trains are regulated within cilia to switch direction specifically at the tip. This research will generate new reagents, assays, and discoveries that will help us to understand cilia as self-organising organelles and give insight into the molecular basis of ciliopathies. I will communicate the results via a molecular movie.
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Membrane proteins comprise a large proportion of all the proteins coded by human and other eukaryotic genomes, and are the targets of more than one-half of all the pharmaceutical drugs marketed today. Knowledge of their three-dimensional structure is important for understanding how they function, and for the development of new drugs for the treatment of diseases. Protein X-ray crystallographic studies, which require well-ordered, large single crystals of the protein, provide such structural information. However, one of the major obstacles to membrane protein structure determinations currently is the ability to produce crystals of a size and quality suitable for single crystal studies. Although often many much smaller crystals can be produced, there has yet to be a method developed to utilise these for the determination of the structure of membrane proteins. The aim of this project is to develop both the methodology and tools necessary to determine the structure of membrane proteins based on samples not of single crystals, but of bunches of very small (microcrystals) using powder diffraction techniques.
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To adapt to the fluid and rapidly-changing social world, human brains have to process social information rapidly and spontaneously. However, most studies so far focus on slow and deliberate social reasoning, with little known about how human brains process social information rapidly and spontaneously, or how such processing develops. I will investigate how human brains react to perceived eye contact, one of the most critical tools for social communication. Firstly, I will compare eye contact processing in healthy adults and patients who have damage to a specific part of their brain, to reveal the cognitive and neural mechanisms underlying eye contact processing. Secondly, I will investigate the development of eye contact processing, by measuring neural responses to eye contact in young infants, comparing British and Japanese individuals, with different cultural norms in relation to the use of eye contact, tracking the development of sighted infants of blind parents, who would have very limited experience of eye contact from their parents, and studying children with autism, who show developmental impairment in social interaction and communication. These studies will shed light on how the human brain effectively deals with a fluid and rapidly-changing social world, and how this ability develops.
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This project examined the connections between literary communities and the emergence of new ideas of colonial citizenship in south-western Nigeria in the decades between the first and second world wars. It aimed to understand the social and cultural world in which a second generation of urban and Christian Yoruba men lived, and how this world intersected with their political activities. There is a rich historiography on the relationship between literacy, the development of the public sphere and ideas of citizenship in Europe from the eighteenth century onwards, but this subject is critically under-researched in early twentieth-century Africa. The importance of the project thus lies in its attempt to explain the cultural content of political movements and organisations in interwar Nigeria which have previously been narrowly interpreted as no more than an early manifestation of nationalism. Three journal articles will be submitted for publication to appear no later than 2007/2008 and they can be expected to have a significant impact in the academic field of African history. In particular, these outputs will likely stimulate further comparative research in the social and cultural histories of South Africa and British West Africa because they draw attention to shared themes in the historiography.
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