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Search results (Displaying 83 grants)

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Earliest award date
24 Jan 2017
Latest award date
27 Nov 2018
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Amount: £1,494,699
Dissecting the neural circuits for visual perceptual learning
<p>Visual perceptual learning (VPL) is an improvement of performance of a visually guided task as a result of visual experience. However, it is not well understood whether improvements are due to changes in lower-level visual or in higher-level association brain areas, and whether improvements can transfer to untrained visual features and tasks.</p> <p>&nbsp;</p> <p>Here I propose to dissect th… more
Amount: £1,317,544
Cellular mechanisms of metabolic sensing by human hypothalamic neurons
<p>Obesity is a major public health problem, but its molecular mechanisms are poorly understood, frustrating efforts to develop broadly effective treatments. Obesity is characterised by abnormal energy homeostasis, which is regulated in large part by hypothalamic melanocortin neurons. The activity of melanocortin neurons is in turn regulated by circulating nutrients and hormones (e.g. leptin), bu… more
Amount: £1,212,840
Epigenetic inheritance: the influence of variable silencing of the repeat genome.
<p>Evidence from epidemiological studies and experiments in animal models suggests that effects of environment and lifestyle can be transmitted across generations via non-genetic mechanisms. Such mechanisms are challenging to unravel in mouse and man. In mammals, non-genetic inheritance is best exemplified by the<em> Agouti viable yellow</em> (<em>Avy</em>) mouse where phenotypic differences in g… more
Amount: £2,929,851
Disorders of Thyroid Hormone Action: Diagnosis, Pathophysiology and Therapy
<p>Having discovered that cystic degeneration of aortic media in human selenoprotein deficiency causes its aneurysmal dilatation, we will elucidate its pathogenesis using mice with conditional, aortic selenoprotein depletion and patients stem cell-derived vascular smooth muscle cells and determine whether antioxidants can inhibit this process. We will investigate structure-function relationships … more
Amount: £1,601,565
Youth, gender and teenage sexual counselling in Britain: The making of the Brook Advisory Centre, 1964-2000
<p>This research uses the history of Brook Advisory Centres (BAC) as a case study through which to reassess the history of teenage sexuality and of the anxieties it caused in postwar Britain. From the first Centre opened in 1964 in London to the present, BAC has been an important provider of contraceptive advice and sexual counselling for unmarried people and teenagers. Although the centres have … more
Amount: £155,453
Principles of human development and germ cell program
<p>Specification of human primordial germ cells (hPGCs)&nbsp;occurs around gastrulation, a critical juncture when the specification of the primary somatic lineages&nbsp;also occurs. In combination with human preimplantation embryos, in<em> vitro</em> models and hPGCs from aborted fetuses, our objective is to elucidate the origin and properties of the early human germline.</p> <p>For&nbsp;the mec… more
Amount: £2,750,000
Contribution of transposable elements in cell fate decision
<p>Transposable elements (TEs) are long known to be expressed in different cells during early mammalian development. However, the role of TEs in cellular differentiation has remained elusive. This proposal aims to develop new experimental and computational methods to understand the role of TEs in cellular differentiation. Single cell (sc) RNA sequencing (RNA-seq) has been developed extensively in… more
Amount: £300,000
Uncovering the roles of dynamic RNA interactions during assembly and assortment of multi-segmented viral genomes
<p>Rotaviruses (RV) comprise a diverse and rapidly evolving group of segmented double-stranded (ds)RNA viruses of the <em>Reoviridae</em> family that cause deadly gastroenteritis in children worldwide. A hallmark of rotavirus morphogenesis is the stoichiometric assembly of eleven distinct genome ssRNA segment precursors prior to packaging. Elucidating the mechanism of accurate &lsquo;molecular co… more
Amount: £1,177,077
The Genetic Basis of Congenital Hypothyroidism
<p>I have already identified 2 novel genetic causal variants for congenital hypothyroidism (CH) by whole exome sequencing (WES); IGSF1 defects in central hypothyroidism and SLC26A7 in dyshormonogenetic CH. I will therefore continue this strategy to identify further genetic causes of CH. I will expand my CH cohort, enriched for probability of genetic mutations. After excluding candidate gene defec… more
Amount: £214,297
Amount: £2,750,000
Amount: £2,610,000
Amount: £2,490,000
Common Variant Genetics of Autism and Autistic Traits (GWAS) Consortium
<p style="margin-left: 0cm; margin-right: 0cm">Autism is a life-long developmental condition with a prevalence of approximately 1%, and heritability estimates of between 64-92%. It is polygenic, with variants across the frequency spectrum (from rare to common) contributing to risk. Considerable progress has been made in identifying rare variants in autism, but the largest genome-wide association … more
Amount: £3,182,054
Evolutionary basis of human diseases in western Eurasia: Insights from ancient genomics
<p>Although large differences in disease susceptibility among present-day human populations have been widely reported, their evolutionary underpinnings remain poorly understood. This project aims to examine how, and to what extent, pathogens shaped disease susceptibility among present-day western Eurasians. We will use whole-genome sequence data from ancient humans and their pathogens to identify… more
Amount: £4,153,544
The proteomic architectures of apicomplexan cells: the molecular complexity of pathogens revealed
<table border="1" cellspacing="0"> <tbody> <tr> <td> <p>Apicomplexan parasites represent highly adapted eukaryotic pathogens that have evolved to exploit multiple human and animal niches causing widespread disease and food deprivation. Key to their success as parasites are novel organelles and structures adapted for invasion and mediation of interactions with their hosts. They have also … more
Amount: £1,687,461
Oxygen and immune response
<p>Our goals are centered on understanding how hypoxic response&nbsp;affects immunity.</p> <p>The experiments described are in&nbsp;three key areas:&nbsp;</p> <p>The first of these is myeloid immunosuppression by hypoxia, and the mechanisms of immunosuppression that are regulated by the&nbsp;hypoxia inducible transcription factor (HIF). Here, we will characterize and determine the range of&nbsp… more
Amount: £2,499,897
Insights into metabolic health and disease from human genetic variants with major functional impact
<p>The metabolism of macronutrients is controlled by the interplay of key organs, including liver, muscle and adipose tissue,&nbsp;orchestrated by hormonal and other signals. Disturbances in this network are associated with metabolic disease. We will build on our experience of using human genetics to illuminate mechanisms of insulin resistance to enhance understanding of the molecular control of … more
Amount: £1,894,039
Coated vesicle adaptors
<p>Coated vesicles transport molecules from one membrane compartment of the cell (a &quot;donor&quot; compartment) to another (&quot;acceptor&quot;) compartment.&nbsp; Adaptors are the components of the coat that select the vesicle cargo. The adaptor protein complexes AP-1 and AP-2 are associated with clathrin-coated vesicles (CCVs), while APs 3, 4, and 5 appear to be clathrin-independent. I have… more
Amount: £1,469,608